Genetika Medikuntza Fakultatean

J.R. Bilbao genetika irakasleak artikulu honetan parte hartzen du.

2011-12-19T10:01:00.003+01:00

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Nature Genetics 43, 1193–1201 (2011)

Gosia Trynka, Karen A Hunt, Nicholas A Bockett, Jihane Romanos, Vanisha Mistry, Agata Szperl, Sjoerd F Bakker, Maria Teresa Bardella, Leena Bhaw-Rosun, Gemma Castillejo, Emilio G de la Concha, Rodrigo Coutinho de Almeida, Kerith-Rae M Dias, Cleo C van Diemen, Patrick C A Dubois, Richard H Duerr, Sarah Edkins, Lude Franke, Karin Fransen, Javier Gutierrez, Graham A R Heap, Barbara Hrdlickova, Sarah Hunt, Leticia Plaza Izurieta, Valentina Izzo, Leo A B Joosten, Cordelia Langford, Maria Cristina Mazzilli, Charles A Mein, Vandana Midah, Mitja Mitrovic, Barbara Mora, Marinita Morelli, Sarah Nutland, Concepción Núñez, Suna Onengut-Gumuscu, Kerra Pearce, Mathieu Platteel, Isabel Polanco, Simon Potter, Carmen Ribes-Koninckx, Isis Ricaño-Ponce, Stephen S Rich, Anna Rybak, José Luis Santiago, Sabyasachi Senapati, Ajit Sood, Hania Szajewska, Riccardo Troncone, Jezabel Varadé, Chris Wallace, Victorien M Wolters, Alexandra Zhernakova, Spanish Consortium on the Genetics ofCoeliac Disease (CEGEC), PreventCDStudy Group, Wellcome Trust CaseControl Consortium (WTCCC), B KThelma, Bozena Cukrowska, Elena Urcelay, Jose Ramon Bilbao, M Luisa Mearin, Donatella Barisani, Jeffrey C Barrett, Vincent Plagnol, Panos Deloukas, Cisca Wijmenga & David A van Heel

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.

Aboriginal Genome Shows Two-Wave Settlement of Asia

2011-09-28T09:25:00.000+02:00

Human Evolutio
Ann Gibbons
Aboriginal Genome Shows Two-Wave Settlement of Asia

Almost a century ago, British anthropologist Alfred Cort Haddon traveled the world seeking samples of human hair, among other curios, for his ethnographic studies of native people. In a remote railway station in southwestern Australia, a young Australian Aboriginal man gave Haddon a lock of his long, reddish-brown hair. Eventually, Haddon took all of the hair back to England, where it lay in a museum drawer for 90 years.

Now in a paper published online this week in Science (http://scim.ag/Abogen), geneticists report that they have extracted enough DNA from that hair to sequence the first complete genome of an Aboriginal.View larger version:Great migrations.DNA from a lock of hair from an Aboriginal Australian like the one pictured above shows that Aboriginal ancestors left Africa and quickly traveled south (orange line) to Melanesia and Australia, interbreeding with Denisovans along the way. Other modern humans (brown line) headed to Asia in a second, later wave. The genome offers the first good look at the origins of Aboriginals, showing that they are one of the oldest continuous populations outside of Africa, says lead author Eske Willerslev, an evolutionary biologist at the University of Copenhagen. It reveals, for example, that the young man's forebears were part of an early wave of modern humans that swept out of Africa at least 60,000 years ago and traveled rapidly by land and sea along the coast of Asia, landing in Australia by some 50,000 years ago. A second wave later populated much of Asia, including China.

Gehiago irakurtzeko....

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

2011-06-01T11:30:00.000+02:00

Nature Genetics 43, 539–546 (2011) doi:10.1038/ng.838

A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10⁻⁸) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10⁻⁹ for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log₁₀ odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.

http://www.nature.com/ng/journal/v43/n6/full/ng.838.html

Artikulu interesgarria

2011-05-26T11:49:00.002+02:00

Transcriptomic analysis of autistic brain reveals convergent molecular pathology

Nature (2011) doi:10.1038/nature10110

Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity^{1, 2, 3}. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain⁴. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.

Artikulu interesgarria

2011-05-26T11:48:00.000+02:00

Royalactin induces queen differentiation in honeybees

Masaki Kamakura Nature 473, 478–483 (26 May 2011) doi:10.1038/nature10093

The honeybee (Apis mellifera) forms two female castes: the queen and the worker. This dimorphism depends not on genetic differences, but on ingestion of royal jelly, although the mechanism through which royal jelly regulates caste differentiation has long remained unknown. Here I show that a 57-kDa protein in royal jelly, previously designated as royalactin, induces the differentiation of honeybee larvae into queens. Royalactin increased body size and ovary development and shortened developmental time in honeybees. Surprisingly, it also showed similar effects in the fruitfly (Drosophila melanogaster). Mechanistic studies revealed that royalactin activated p70 S6 kinase, which was responsible for the increase of body size, increased the activity of mitogen-activated protein kinase, which was involved in the decreased developmental time, and increased the titre of juvenile hormone, an essential hormone for ovary development. Knockdown of epidermal growth factor receptor (Egfr) expression in the fat body of honeybees and fruitflies resulted in a defect of all phenotypes induced by royalactin, showing that Egfr mediates these actions. These findings indicate that a specific factor in royal jelly, royalactin, drives queen development through an Egfr-mediated signalling pathway.

Gene therapy finds its niche

2011-02-10T15:36:00.000+01:00

Gene therapy finds its niche

Cormac Sheridan
Nature Biotechnology 29, 121–128 (2011) doi:10.1038/nbt.1769

Published online 07 February 2011

Gene therapy is finally poised to make a contribution to the treatment of debilitating, highly penetrant genetic diseases that have proved intractable to other regimens.

A growing body of evidence for the effectiveness of a select set of gene therapies in certain debilitating conditions is restoring the reputation of a field previously beset by heartbreaking mishaps and forsaken by investors. Positive human efficacy data in a lengthening list of inherited conditions, such as Leber's congenital amaurosis, X-linked adrenoleukodystrophy (ALD), β-thalassemia and severe combined immunodeficiency (SCID), previously intractable to treatment have contributed to a growing sense that the promise of gene therapy is—after several false starts—finally being realized. That optimism is tempered by a sense of pragmatism gained through the many disappointments and setbacks the sector has endured. Even so, despite several clinical development programs progressing to late-stage trials (Table 1), the gene therapy community will likely have to wait 12 months or more before a product gains regulatory approval in Europe, let alone the United States.

Gehiago irakurri nahi baduzu....

Bifiduak jan behar?

2011-01-28T10:18:00.000+01:00

Bifidobacteria can protect from enteropathogenic infection through production of acetate

Nature 469, 543–547 (27 January 2011) doi:10.1038/nature09646

The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology^{1, 2, 3}. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases^{4, 5, 6}. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated ‘omics’ approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.

Ebook gehiago

2011-01-26T18:18:00.000+01:00

Proteins and Gene Expression

Cell Cycle and Cell Division Cell Cycle and Cell Division (ebook)

2011-01-26T18:16:00.000+01:00

Cell Cycle and Cell Division

Essentials of Genetics (ebook)

2011-01-26T18:14:00.000+01:00

Link honetan

Essentials of Genetics ebook-a aurkituko duzu

Oso informazio interesgarria "Nature ebooks"

2010-12-20T14:07:00.000+01:00

Nature ebooks

Fisikako nobel saria: Izugarria!!!!!

2010-10-06T09:43:00.000+02:00

Historia de un descubrimiento

ELSA PRADA 06/08/2010

Hace poco más de cinco siglos, Colón buscó una ruta alternativa para llegar a las deseadas Indias. Con grandes esfuerzos (y falta de confianza de sus contemporáneos), marchó en la dirección contraria a la del resto de navegantes. En el camino, sin esperarlo, hizo un descubrimiento que cambiaría el futuro de la humanidad. La historia nace a menudo de iniciativas que desafían el camino establecido, de personas que se aventuran en la otra dirección.

Nobel de Física para dos científicos rusos por sus trabajos sobre el grafeno

El grafeno era hasta hace poco una quimera, un modelo usado por los físicos que nunca se había sintetizado

Es la membrana más fina posible, pues es carbono de un átomo de grosor, y tiene la apariencia de una tela

Esta actitud es la que llevó hace seis años al descubrimiento de un material que amenaza con revolucionar el mundo de la tecnología. El grafeno era hasta hace poco una quimera, un modelo teórico usado por los físicos que nunca se había logrado sintetizar. Se trata de la membrana más fina posible, pues es carbono de un átomo de grosor, y tiene la apariencia de una tela transparente y flexible, a la par que resistente y conductora de electricidad. El carbono del que está hecho es un elemento fascinante, pues si bien es muy común (nosotros mismos estamos compuestos en gran parte de carbono), da lugar a muy diversos materiales tan solo cambiando la forma en la que unos átomos se unen a otros. Cuando se empaqueta densamente en una estructura tridimensional, tenemos un diamante. Cuando se organiza en capas bidimensionales débilmente unidas, tenemos grafito, con el que se fabrican las minas de los lápices.
Pues bien, para comprender el grafito y sus derivados, los físicos llevaban 50 años estudiando las propiedades matemáticas del grafeno. Una de ellas era precisamente la de que un material así no podía existir. Se pensaba que, si se conseguía aislar una sola capa de grafito, estaría tan llena de defectos que sería inestable a temperatura ambiente. En 2004, el físico Andre Geim, de la Universidad de Manchester, buscaba una nueva línea de investigación para un estudiante de doctorado que acababa de llegar. No siempre es fácil tener a mano un tema nuevo. Konstantin Kostya Novoselov, que así se llamaba el recién llegado, iba a aparecer en su despacho en cualquier momento y no sabía qué ofrecerle. Entonces tuvo una idea. Otro de sus estudiantes estaba investigando el grafito. Para el estudio de este material, es necesario que su superficie esté lo más pulida y limpia posible. Para ello, en estos laboratorios de alta tecnología se usa un método bastante rudimentario. Simplemente se pega un trozo de cinta adhesiva sobre la muestra y se tira con garbo. De esta forma se arrancan las capas más superficiales, que suelen estar dañadas y contaminadas, y se analiza el grafito restante. Las cintas de celo usadas para el pulido se tiran sin más. Sin embargo, en un giro genial, a Andre se le ocurrió mirar en esa otra dirección, la de los restos pegados al celo, y proponerle a Kostya el estudio de las capas de grafito que normalmente se desechan. Lo que ninguno de los dos se imaginaba es que, entre los cientos de laminillas pegadas a la cinta, algunas serían monocapas cristalinas de grafito, o sea, grafeno, cuyas propiedades revolucionarían la física de los materiales.
El grupo de Manchester consiguió medidas de transporte electrónico a través de grafeno. Con estos resultados viajaron a EE UU y los presentaron en la reunión anual más famosa de físicos de la materia condensada, el March Meeting. Sabían que tenían unos resultados nuevos y con potencial en el mundo de las aplicaciones tecnológicas, pero no se imaginaban que sus medidas guardaban aún más sorpresas, esta vez de carácter fundamental y filosófico.
Casualmente, en 2005, un importante profesor español y experto en grafito disfrutaba de un año sabático en la Universidad de Boston. Francisco Paco Guinea, del Instituto de Ciencia de Materiales de Madrid, y otros dos colegas, Antonio Castro Neto y Nuno Peres, vieron los resultados de Kostya y se dieron cuenta de que no solo se hallaban ante una proeza experimental, sino ante un hito en el campo de la física. Resulta que los electrones del grafeno se comportan de una manera muy especial. No se rigen por las ecuaciones que usualmente describen el comportamiento de materiales normales, como los semiconductores o los metales, sino que se parecen a los de partículas muy difíciles de generar y detectar, para cuyo estudio se construyen gigantescos aceleradores de partículas como el LHC de Ginebra. Gracias en gran parte a la visión de Paco, el grafeno nos brinda la posibilidad de acceder a esta física de altos vuelos con pocos medios y desde el modesto laboratorio de una universidad.
Además de las aplicaciones de microelectrónica y pantallas, otras propuestas incluyen paneles solares y supercapacitores (baterías que se recargan al instante). Desde la biotecnología se ha pensado en usarlo para encapsular virus. Son tan solo algunos ejemplos. Lo que está claro es que, en su corta vida, el grafeno ha capturado la imaginación de científicos de todo el mundo. Y promete dar mucho más que hablar.

Elsa Prada es investigadora en grafeno en el Instituto de Ciencia de Materiales del CSIC de Madrid.

The Nobel Prize in Physiology or Medicine 2010

2010-10-04T12:35:00.000+02:00

Press Release 2010-10-04

Robert G. Edwards

for the development of in vitro fertilization

Summary

Robert Edwards is awarded the 2010 Nobel Prize for the development of human in vitro fertilization (IVF) therapy. His achievements have made it possible to treat infertility, a medical condition afflicting a large proportion of humanity including more than 10% of all couples worldwide.

As early as the 1950s, Edwards had the vision that IVF could be useful as a treatment for infertility. He worked systematically to realize his goal, discovered important principles for human fertilization, and succeeded in accomplishing fertilization of human egg cells in test tubes (or more precisely, cell culture dishes). His efforts were finally crowned by success on 25 July, 1978, when the world's first "test tube baby" was born. During the following years, Edwards and his co-workers refined IVF technology and shared it with colleagues around the world.

Approximately four million individuals have so far been born following IVF. Many of them are now adult and some have already become parents. A new field of medicine has emerged, with Robert Edwards leading the process all the way from the fundamental discoveries to the current, successful IVF therapy. His contributions represent a milestone in the development of modern medicine.
Infertility – a medical and psychological problem

More than 10% of all couples worldwide are infertile. For many of them, this is a great disappointment and for some causes lifelong psychological trauma. Medicine has had limited opportunities to help these individuals in the past. Today, the situation is entirely different. In vitro fertilization (IVF) is an established therapy when sperm and egg cannot meet inside the body.
Basic research bears fruit

The British scientist Robert Edwards began his fundamental research on the biology of fertilization in the 1950s. He soon realized that fertilization outside the body could represent a possible treatment of infertility. Other scientists had shown that egg cells from rabbits could be fertilized in test tubes when sperm was added, giving rise to offspring. Edwards decided to investigate if similar methods could be used to fertilize human egg cells.

It turned out that human eggs have an entirely different life cycle than those of rabbits. In a series of experimental studies conducted together with several different co-workers, Edwards made a number of fundamental discoveries. He clarified how human eggs mature, how different hormones regulate their maturation, and at which time point the eggs are susceptible to the fertilizing sperm. He also determined the conditions under which sperm is activated and has the capacity to fertilize the egg. In 1969, his efforts met with success when, for the first time, a human egg was fertilized in a test tube.

In spite of this success, a major problem remained. The fertilized egg did not develop beyond a single cell division. Edwards suspected that eggs that had matured in the ovaries before they were removed for IVF would function better, and looked for possible ways to obtain such eggs in a safe way.
From experiment to clinical medicine

Edwards contacted the gynecologist Patrick Steptoe. He became the clinician who, together with Edwards, developed IVF from experiment to practical medicine. Steptoe was one of the pioneers in laparoscopy, a technique that was new and controversial at the time. It allows inspection of the ovaries through an optical instrument. Steptoe used the laparoscope to remove eggs from the ovaries and Edwards put the eggs in cell culture and added sperm. The fertilized egg cells now divided several times and formed early embryos, 8 cells in size (see figure).

These early studies were promising but the Medical Research Council decided not to fund a continuation of the project. However, a private donation allowed the work to continue. The research also became the topic of a lively ethical debate that was initiated by Edwards himself. Several religious leaders, ethicists, and scientists demanded that the project be stopped, while others gave it their support.
The birth of Louise Brown - an historic event

Edwards and Steptoe could continue their research thanks to the new donation. By analyzing the patients' hormone levels, they could determine the best time point for fertilization and maximize the chances for success. In 1978, Lesley and John Brown came to the clinic after nine years of failed attempts to have a child. IVF treatment was carried out, and when the fertilized egg had developed into an embryo with 8 cells, it was returned to Mrs. Brown. A healthy baby, Louise Brown, was born through Caesarian section after a full-term pregnancy, on 25 July, 1978. IVF had moved from vision to reality and a new era in medicine had begun.
IVF is refined and spreads around the world

Edwards and Steptoe established the Bourn Hall Clinic in Cambridge, the world's first centre for IVF therapy. Steptoe was its medical director until his death in 1988, and Edwards was its head of research until his retirement. Gynecologists and cell biologists from all around the world trained at Bourn Hall, where the methods of IVF were continuously refined. By 1986, 1,000 children had already been born following IVF at Bourn Hall, representing approximately half of all children born after IVF in the world at that time.

Today, IVF is an established therapy throughout the world. It has undergone several important improvements. For example, single sperm can be microinjected directly into the egg cell in the culture dish. This method has improved the treatment of male infertility by IVF. Furthermore, mature eggs suitable for IVF can be identified by ultrasound and removed with a fine syringe rather than through the laparoscope.

IVF is a safe and effective therapy. 20-30% of fertilized eggs lead to the birth of a child. Complications include premature births but are very rare, particularly when one egg only is inserted into the mother. Long-term follow-up studies have shown that IVF children are as healthy as other children.

Approximately four million individuals have been born thanks to IVF. Louise Brown and several other IVF children have given birth to children themselves; this is probably the best evidence for the safety and success of IVF therapy. Today, Robert Edwards' vision is a reality and brings joy to infertile people all over the world.

Robert G. Edwards was born in 1925 in Manchester, England. After military service in the Second World War, he studied biology at the University of Wales in Bangor and at Edinburgh University in Scotland, where he received his PhD in 1955 with a Thesis on embryonal development in mice. He became a staff scientist at the National Institute for Medical Research in London in 1958 and initiated his research on the human fertilization process. From 1963, Edwards worked in Cambridge, first at its university and later at Bourn Hall Clinic, the world's first IVF centre, which he founded together with Patrick Steptoe. Edwards was its research director for many years and he was also the editor of several leading scientific journals in the area of fertilization. Robert Edwards is currently professor emeritus at the University of Cambridge.

References:

Edwards RG. Maturation in vitro of human ovarian oocytes. Lancet 1965; 2:926-929.

Edwards RG, Bavister BD, Steptoe PC. Early stages of fertilization in vitro of human oocytes matured in vitro. Nature 1969; 221:632-635.

Edwards RG, Steptoe PC, Purdy JM. Fertilization and cleavage in vitro of human oocytes matured in vivo. Nature 1970; 227:1307-1309.

Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978; 2:366.

Edwards RG. The bumpy road to human in vitro fertilization. Nature Med 2001; 7:1091-4.

Ingurunearen eragina pertsona heterozigotoetan

2010-10-01T11:43:00.000+02:00

Revista Clínica Española

Fiebre y dolor abdominal tras el ascenso al Teide

Por A Martín-Armas a, B J Anía b

a Servicio de Medicina Interna. Hospital Universitario de Gran Canaria Dr. Negrín.

b Servicio de Medicina Interna. Hospital Universitario de Gran Canaria Dr. Negrín. Universidad de Las Palmas de Gran Canaria. España.

Caso clínico

Presentamos el caso de un varón de 42 años, sin antecedentes patológicos, senderista profesional de la isla de Gran Canaria.

Tras su primer ascenso a pie a la cumbre del Teide (3.718 metros), durante el descenso present&oa ...

Rev Clin Esp. 2008;208:259-61.

Caso clínico

Presentamos el caso de un varón de 42 años, sin antecedentes patológicos, senderista profesional de la isla de Gran Canaria.

Tras su primer ascenso a pie a la cumbre del Teide (3.718 metros), durante el descenso presentó vómitos repetidos y dolor hipogástrico. Al día siguiente acudió a Urgencias aquejado de dolor en hipocondrio izquierdo irradiado al hombro, que aumentaba con la inspiración, y fiebre de hasta 39 °C. No había tenido cefalea, tos, diarrea, ni molestias urinarias.

En la exploración destacaba hipoventilación en base izquierda, auscultación cardiaca normal, abdomen difusamente doloroso a la palpación sin visceromegalias, y puñopercusión lumbar izquierda dolorosa.

La analítica presentaba leucocitosis de 22.460 (84,6% neutrófilos, 4,5% linfocitos y 10,8% monocitos) con presencia de linfocitos estimulados en el frotis, hemoglobinemia de 12,3 g/dl, creatinquinasa de 462 U/l, urea y creatinina normales, y urinálisis sin alteraciones. La radiografía de tórax mostraba una elevación del hemidiafragma izquierdo (figs. 1A y 1B). En la ecografía abdominal destacaba una esplenomegalia (14 cm de diámetro interpolar) con patrón micronodular hiperecogénico. En la tomografía computarizada (TC) toracoabdominal con contraste se apreciaba atelectasia subsegmentaria de lóbulo inferior izquierdo y esplenomegalia con hipoatenuación (fig. 2).

Fig. 1. Radiografías de tórax posteroanterior (A) y lateral (B) en las que se aprecia solamente elevación del hemidiafragma izquierdo.

Fig. 2. Tomografía computarizada toracoabdominal con contraste donde se aprecia atelectasia subsegmentaria de lóbulo inferior izquierdo y esplenomegalia con marcada hipoatenuación.

Durante su ingreso evolucionó de forma favorable con tratamiento analgésico y sin antibióticos, desapareciendo la febrícula a los dos días. Todos los estudios microbiológicos fueron negativos.

Una nueva TC abdominal con contraste a los 12 días de la primera mostró una disminución del tamaño del bazo (11 cm), con persistencia de la hipoperfusión del mismo y una imagen triangular de mayor hipoatenuación (fig. 3).

Fig. 3. Tomografía computarizada abdominal con contraste mostrando un área triangular de mayor hipoatenuación en el polo superior esplénico sugestiva de necrosis.

Una resonancia magnética (RM) abdominal realizada a las 4 semanas del inicio de los síntomas demostró un infarto esplénico sin signos de trombosis esplénica arterial ni venosa (figs. 4A, 4B y 4C).

Fig. 4. Resonancia magnética abdominal con contraste en secuencia T1 con supresión grasa en fase arterial (A) y en fase venosa (B), y en secuencia T2 (C) demostrando infarto esplénico sin signos de trombosis esplénica arterial ni venosa.

Evolución posterior

El estudio de trombofilia mostró normalidad de los inhibidores de la coagulación e inexistencia de factores procoagulantes anormales. Una electroforesis de hemoglobina realizada al detectarse incidentalmente una hemoglobinemia de 11,8 g/dl encontró 39,8% de HbS y 50,0% de HbA. La prueba de falciformación resultó positiva. El paciente era de raza blanca, no tenía antecedentes familiares de hemoglobinopatías, y su familia paterna era de origen sefardí.

El paciente incrementó de forma paulatina los esfuerzos hasta el punto de que, a los 5 meses del episodio, realizaba su trabajo sin problemas.

Diagnóstico

Infarto esplénico de las grandes alturas en paciente con rasgo falciforme.

Discusión

En contraposición a la anemia falciforme o drepanocitosis (del griego δρεπανον , hoz), el rasgo drepanocítico raras veces produce sintomatología o alteraciones del hemograma, a menos que las condiciones ambientales produzcan hipoxia o deshidratación. El rasgo falciforme afecta al 25% de la población negra africana, aunque también puede encontrarse con mucha menor frecuencia en población autóctona de España, Italia y Grecia ¹. Los portadores del rasgo, a menos que tengan antecedentes familiares, desconocen su condición ². El diagnóstico se realiza mediante electroforesis de la hemoglobina, encontrándose habitualmente una proporción ligeramente menor de HbS que de HbA. El síntoma más característico, aunque infrecuente, es la hematuria indolora. Más raros son los cólicos nefríticos por necrosis papilar, y aún más raros los casos de falciformación masiva con crisis dolorosas, secuestro esplénico, o síndrome torácico agudo ³.

Dado que el paciente es senderista profesional, sorprende que no haya tenido síntomas hasta la fecha. Hay que reseñar, sin embargo, que el punto más alto de la isla de Gran Canaria, en la que reside y trabaja, es el pico Pozo de las Nieves (1.949 m). Y las personas con rasgo falciforme que vuelan en aviones comerciales son expuestas a presiones en cabina de hasta 8.000 pies (2.438 m), sin que se hayan descrito síntomas por este motivo ⁴.

No se ha observado diferencia entre personas con rasgo falciforme y controles normales en la respuesta pulmonar a la hipoxia ⁵ o en la tolerancia al ejercicio en altura⁶. Aparte de la hipoxemia, el más decisivo de los factores que pueden influir en la falciformación in vivo en personas con rasgo falciforme parece ser la deficiente hidratación durante el ejercicio en ambiente caluroso ⁷. Pero el entrenamiento puede proteger a los portadores de rasgo falciforme de los estreses fisiológicos que pueden inducir falciformación ⁸.

El infarto esplénico de las grandes alturas en portadores de rasgo falciforme parece ser más frecuente en personas de raza blanca ⁹ y suele responder bien al tratamiento de soporte, por lo cual debe evitarse la esplenectomía ². Un infarto esplénico en un muchacho de 13 años de raza blanca con rasgo falciforme tras el ascenso en teleférico al Teide y buena evolución sin esplenectomía fue descrito en España hace 25 años ¹⁰.

El presente caso nos viene a recordar que las hemopatías no malignas son una causa posible, aunque infrecuente, de fiebre.

Bibliografía

1. Hernández Nieto L, Hernández García MT, Juncà Piera J, Vives-Corrons JL, Martín-Vega C. Enfermedades del sistema eritrocitario: anemias. En: Rozman C, editor. Medicina Interna. Madrid: Elsevier; 2004. p.1644-69.
2. Sheikha A. Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary. Can J Surg. 2005;48(5):377-81.[Medline]
3. Benz EJ. Hemoglobinopathies. En: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, editores. Principles of Internal Medicine. New York: McGraw-Hill; 2005. p. 593-601.
4. Aerospace Medical Association Medical Guidelines Task Force. Medical Guidelines for Airline Travel. Aviat Space Environ Med. 2003;74 (5 Suppl):A1-A19.
5. Dillard TA, Kark JA, Rajagopal KR, Key JA, Canik JJ, Ruehle CJ. Pulmonary function in sickle cell trait. Ann Intern Med. 1987;106(2):191-6.[Medline]
6. Nuss R, Loehr JP, Daberkow E, Graham L, Lane PA. Cardiopulmonary function in men with sickle cell trait who reside at moderately high altitude. J Lab Clin Med. 1993;122(4):382-7.[Medline]
7. Bergeron MF, Cannon JG, Hall EL, Kutlar A. Erythrocyte sickling during exercise and thermal stress. Clin J Sport Med. 2004;14(6):354-6.[Medline]
8. Monchanin G, Connes P, Wouassi D, Francina A, Djoda B, Banga PE, et al.Hemorheology, sickle cell trait, and alpha-thalassemia in athletes: effects of exercise. Med Sci Sports Exerc. 2005;37(7):1086-92.[Medline]
9. Lane PA, Githens JH. Splenic syndrome at mountain altitudes in sickle cell trait. Its occurrence in nonblack persons. JAMA. 1985;253(15): 2251-4.
10. Callís M, Petit JJ, Jordan C. Splenic infarction in a white boy with sickle cell trait. Acta Haematol. 1982;67(3):232.[Medline
]

Poster bat nola egin

2010-09-24T11:57:00.000+02:00

Advice on designing scientific posters

Colin Purrington, Department of Biology, Swarthmore College, Pennsylvania

A one-sentence overview of the poster concept
A scientific poster is a large document that can communicate your research at a scientific meeting, and is composed of a short title, an introduction to your burning question, an overview of your trendy experimental approach, your amazing results, some insightful discussion of aforementioned results, a listing of previously published articles that are important to your research, and some brief acknowledgement of the tremendous assistance and financial support conned from others—if all text is kept to a minimum, a person could fully read your poster in under 10 minutes.

Aldizkari interesgarri bat

2010-09-22T12:12:00.000+02:00

Journal of Inherited Metabolic Disease

Gene therapy: Targeting β-thalassaemia

2010-09-16T11:52:00.001+02:00

Gene therapy: Targeting β-thalassaemia

Derek A. Persons Nature 467,277–278(16 September 2010)

β-Thalassaemia is one of several inherited disorders associated with abnormalities in the oxygen-carrying protein haemoglobin. It is caused by mutations in the β-globin chain of haemoglobin that lead to ineffective production of red blood cells and profound anaemia. Patients with β-thalassaemia require regular blood transfusions for life. Chronic transfusions have a significant impact on the quality of life and ultimately shorten life expectancy. As for treating this disorder, until now the only available strategy has been the transplantation of bone-marrow cells, a procedure whose success depends on the availability of suitable donors. A therapy based on genetic correction of a patient's own bone-marrow cells has therefore long been awaited1. On page 318 of this issue, Cavazzana-Calvo et al.2 deliver news of one such success story using gene therapy.

Open Access Journal interesgarria "Orphanet Journal of Rare Diseases"

2010-09-13T12:36:00.003+02:00

Orphanet Journal of Rare Diseases is an open access, online journal that encompasses all aspects of rare diseases and orphan drugs. The journal publishes high quality reviews on specific rare diseases. In addition, the journal may consider articles on research findings and clinical trial outcome reports, either positive or negative, and articles on public health issues in the field of rare diseases and orphan drugs.

http://www.ojrd.com/articles/browse.asp

Ikasturte berria martxan

2010-09-09T12:50:00.000+02:00

Ikasturte berria martxan dago eta ea jarraitzen dudan txintxo-txintxo gauza interesgarriak aurkitzen.

Bideo interesgarria

2010-06-01T15:32:00.004+02:00

Artikulu interesgarria

2010-05-13T10:50:00.000+02:00

Published online 12 May 2010 | Nature 465, 148-149 (2010) | doi:10.1038/465148a

News

Ancient DNA set to rewrite human history

Discovery that some humans are part-Neanderthal reveals the promise of comparing genomes old and new.

Rex Dalton

The worlds of ancient and modern DNA exploration have collided in spectacular fashion in the past few months. Last week saw the publication of a long-awaited draft genome of the Neanderthal, an archaic hominin from about 40,000 years ago¹. Just three months earlier, researchers in Denmark reported the genome of a 4,000-year-old Saqqaq Palaeo-Eskimo² that was plucked from the Greenland permafrost and sequenced in China using the latest technology.

Neanderthals once bred with Homo sapiens.PHOTOLIBRARY

As researchers compare these ancient genomes with the ever-expanding number from today's humans, they expect to gain insights into human evolution and migration — with more discoveries to come as they decipher DNA from other branches of the human evolutionary tree. "For the first time, ancient and modern genetic research is going hand in hand," says Eske Willerslev, whose team at the University of Copenhagen led the Palaeo-Eskimo sequencing project. "It is really a fantastic time."
Already, analysis of the Neanderthal genome has helped to resolve a debate about whether there was interbreeding between Neanderthals and Homo sapiens: genome comparisons suggest that the two groups mated an estimated 45,000–80,000 years ago in the eastern Mediterranean area. The sequencing study, from a consortium led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, found that the genomes of non- African H. sapiens today contain around 1–4% of sequence inherited from Neanderthals.

Gehiago irakurri nahi baduzu....

Artikulu interesgarria

2010-05-13T10:36:00.000+02:00

Genetics: An eye for colour

Journal name:NatureVolume:465,Page:138Date published:(13 May 2010)DOI:doi:10.1038/465138e

Published online 12 May 2010 Cited research: PLoS Genet. 6, e1000934 (2010)

Previous studies of the genetics of human eye colour used only broad categories — such as blue, brown and intermediate — without quantifying the subtle variations in between. So far, this has led to the identification of seven genes associated with the trait.
Manfred Kayser at Erasmus University Medical Center in Rotterdam, the Netherlands, and his colleagues adopted a more detailed approach. They digitally encoded eye colour using hue and saturation values obtained from high-resolution photographs of 5,951 Dutch Europeans.
Analysis of the participants' genomes revealed three new regions associated with continuous variations in eye colour. These new regions, together with the seven genes identified previously, underlie about 50% of eye-colour variation, according to a model the researchers developed to predict eye colour. J.F.

Artikulu interesgarria

2010-05-10T10:56:00.002+02:00

Hum Genet. 2010 May 5.

High-density SNP genotyping detects homogeneity of Spanish and French Basques, and confirms their genomic distinctiveness from other European populations.

Rodríguez-Ezpeleta N, Alvarez-Busto J, Imaz L, Regueiro M, Azcárate MN, Bilbao R, Iriondo M, Gil A, Estonba A, Aransay AM.

Genome Analysis Platform, Functional Genomics Unit, CIC bioGUNE, Bizkaia Technology Park, Building 502, 48160, Derio, Spain, nrodriguez@cicbiogune.es.

Abstract

A recent study reported that Basques do not constitute a genetically distinct population, and that Basques from Spanish and French provinces do not show significant genetic similarity. These conclusions disagree with numerous previous studies, and are not consistent with the historical and linguistic evidence that supports the distinctiveness of Basques. In order to further investigate this controversy, we have genotyped 83 Spanish Basque individuals and used these data to infer population structure based on more than 60,000 single nucleotide polymorphisms of several European populations. Here, we present the first high-throughput analysis including Basques from Spanish and French provinces, and show that all Basques constitute a homogeneous group that can be clearly differentiated from other European populations.

Artikulu interesgarria

2010-04-15T16:09:00.002+02:00

Nature 464, 989-990 (15 April 2010) | doi:10.1038/464989a; Published online 14 April 2010

Cancer: Genomics of metastasis

Joe Gray¹

Cancer cells that invade other parts of the body do so by accumulating genomic aberrations. Analysis of the genomic differences between primary and metastatic tumours should aid the understanding of this process.

The massively parallel sequencing technologies now available are sufficiently powerful and cost-effective to allow high-resolution analysis of changes that occur in the genome of patients with cancer. These include variations in the number of copies of specific genomic regions, changes in DNA sequence, and structural aberrations^1,^2,³. On page 999 of this issue, Ding et al.⁴ report their application of this technology to analyse the genomic features of primary and metastatic tumour samples from a 44-year-old African-American patient with basal-like breast cancer. Their results provide insight into how cancer genomes evolve as the disease progresses.

The way in which tumour cells escape their primary site and colonize other locations in the body — often with lethal results — is becoming increasingly clear^5,^6,^7,⁸. Underlying biological changes include variations in cell differentiation, in the ability to sense cell-death signals, in cell-cycle regulation and in genome stability. Other hallmarks of tumour-cell metastasis are increased cell motility and invasion, new blood-vessel formation and inflammation.

Gehiago irakurri nahi baduzu...

Artikulu interesgarria

2010-04-15T15:59:00.002+02:00

Published online 14 April 2010 | Nature 464, 972-974 (2010) | doi:10.1038/464972a

News Feature

Big science: The cancer genome challenge

Databases could soon be flooded with genome sequences from 25,000 tumours. Heidi Ledford looks at the obstacles researchers face as they search for meaning in the data.

Heidi Ledford

Download a pdf of this story.

When it was first discovered, in 2006, in a study of 35 colorectal cancers¹, the mutation in the gene IDH1 seemed to have little consequence. It appeared in only one of the tumours sampled, and later analyses of some 300 more have revealed no additional mutations in the gene. The mutation changed only one letter of IDH1, which encodes isocitrate dehydrogenase, a lowly housekeeping enzyme involved in metabolism. And there were plenty of other mutations to study in the 13,000 genes sequenced from each sample. "Nobody would have expected IDH1 to be important in cancer," says Victor Velculescu, a researcher at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Maryland, who had contributed to the study.
But as efforts to sequence tumour DNA expanded, the IDH1 mutation surfaced again: in 12% of samples of a type of brain cancer called glioblastoma multiforme², then in 8% of acute myeloid leukaemia samples³. Structural studies showed that the mutation changed the activity of isocitrate dehydrogenase, causing a cancer-promoting metabolite to accumulate in cells⁴. And at least one pharmaceutical company — Agios Pharmaceuticals in Cambridge, Massachusetts — is already hunting for a drug to stop the process.

Gehiago irakurri nahi baduzu....

Artikulu interesgarria

2010-04-15T15:54:00.002+02:00

Nature 464, 978-979 (15 April 2010) | doi:10.1038/464978a; Published online 14 April 2010

Let parents decide

Alan Handyside¹

Top

Twenty years on from the first pregnancies after preimplantation genetic diagnosis, Alan Handyside argues that informed prospective parents are largely good guides to the use of the thriving technology.

Twenty years ago this month, my colleagues and I published a paper in Nature describing how our small team at Hammersmith Hospital in London helped to bring about the first pregnancies following preimplantation genetic diagnosis (PGD). We used the technique in several couples. They risked having children with serious inherited diseases linked to the X chromosome that typically affect boys, such as Duchenne muscular dystrophy. After fertilizing the eggs in vitro and testing to identify gender, we implanted only unaffected female embryos.

A few days later, the House of Commons passed the Human Fertilisation and Embryology Bill. As well as regulating fertility treatment, the act sanctioned research on early human embryos, which, as our Nature study demonstrated (A. H. Handyside et al. Nature 344, 768–770; 1990), could have profound clinical benefits. Since then, the act has been updated several times by court judgments, and was amended completely in 2008, to keep pace with changing social attitudes and with rapid developments in fertility treatment and embryo research. Among other things, the 2008 act allows the creation of animal–human hybrid embryos, approves the use of PGD to create 'saviour siblings' and bans the use of gender selection for non-medical reasons.

Gehiago irakurri nahi baduzu...

Tekniken inguruko animazioak

2010-03-10T10:16:00.001+01:00

http://learn.genetics.utah.edu/content/labs/microarray/

http://www.dnalc.org/resources/animations/cycseq.html

Genetikaren inguruko hainbat animazio

2010-03-10T10:02:00.002+01:00

http://www.phgfoundation.org/tutorials/home/

Sanger sekuentziazio metodoa

2010-03-10T09:49:00.002+01:00

DNAren elektroforesia

2010-03-08T10:54:00.002+01:00

http://www.youtube.com/watch?v=kTsrPIdzbVY

Genetics: Random expression goes binary

2010-02-18T09:42:00.000+01:00

Nature 463, 891-892 (18 February 2010) | doi:10.1038/463891a; Published online 17 February 2010

Genetics: Random expression goes binary

Adrian Streit¹ & Ralf J. Sommer¹

The production of intestinal cells in a worm embryo is regulated by a network of transcription factors. Studies of these networks in mutant worms provide evidence for stochastic effects in gene expression.

Identical twins are not truly identical. Although to strangers they look very much alike, relatives and friends usually have no problem telling them apart, even from a distance, and they have their own personalities. It is also known that not all carriers of mutations that cause genetic disorders develop the associated disease. Similarly, there are many cases in which only a fraction of a population of organisms that harbours a mutation at a particular genetic locus develops the corresponding mutant characteristics (phenotypes); the rest are of wild-type appearance. This phenomenon, known as incomplete penetrance, indicates the existence of a mechanism that generates diversity even among genetically identical individuals.

Such variability can often be explained by differences in genetic background in non-identical organisms, or by the exposure of individuals to different environmental conditions. But incomplete penetrance is also observed in genetically identical populations of laboratory animals, which are kept under controlled, stable conditions. It has therefore long been assumed that the phenomenon is partly caused by stochastic events, in particular random fluctuations in gene expression, which must reach some threshold level to cause an outcome¹. That would explain the binary, 'on–off' nature of the effect. But convincing, experimentally validated examples of a stochastic process are scarce.

On page 913 of this issue, Raj et al.² provide just such evidence. They report that the incomplete penetrance of mutations in the gene skn-1, which induces the differentiation of intestinal cells in the nematode Caenorhabditis elegans (Fig. 1), can be explained if the randomly fluctuating expression of a downstream gene, end-1, must reach a certain threshold to exert its effect.

Africa yields two full human genomes

2010-02-18T09:33:00.001+01:00

Published online 17 February 2010 | Nature 463, 857 (2010) | doi:10.1038/463857a

News

Sequences show rich diversity among the population.

Heidi Ledford

Archbishop Desmond Tutu's genome was chosen to represent the Bantu peoples of southern Africa.

To the growing list of people with fully sequenced genomes, two memorable names have now been added: Archbishop Desmond Tutu, the South African civil-rights activist, and !Gubi, a Namibian hunter-gatherer.

!Gubi hails from the Khoisan community, one of the most ancient and diverse human populations. His is the first genome from a minority population in Africa to be sequenced. Comparing his sequence with the partial genome sequences of three other Khoisan shows that they are as different from one another as a European would be from an Asian, says team leader Stephan Schuster, a genome researcher at Pennsylvania State University in University Park. "This is despite the fact that they sometimes live within walking distance of one another," he adds.

These sequences are published today in Nature (see Nature 463, 943-947; 2010) along with Tutu's, whose DNA was sequenced as a point of comparison because he comes from the Bantu, the majority population in southern Africa. The data could provide the tools needed to tackle some of the most fundamental questions of human evolution: where did modern humans originate in Africa? How long ago? When did the original migrations out of Africa occur, and who were the migrants?

Gehiago irakurri nahi baduzu...

Evolutionary biology: Face of the past reconstructed

2010-02-11T12:32:00.000+01:00

Nature 463, 739-740 (11 February 2010) | doi:10.1038/463739a; Published online 10 February 2010

Evolutionary biology: Face of the past reconstructed

David M. Lambert &Leon Huynen

Abstract

DNA is particularly well preserved in hair — enabling the genome of a human to be sequenced, and his ancestry and appearance to be determined, from 4,000-year-old remains.

The impact of the Human Genome Project (HGP)1 and the development of 'mega-DNA sequencers' continue to have ramifications in diverse fields. An excellent example is reported on page 757 of this issue by Rasmussen et al.2, who describe the first genome sequence of an ancient human. Their work was made possible only by the technical advances seen since the HGP. The authors used bioinformatics tools, databases and molecular-biology techniques to uncover a great deal of information about this ancient person.

Rasmussen et al.2 recovered DNA from a tuft of 4,000-year-old human hair preserved in permafrost at Qeqertasussuk, Greenland. The hair came from an individual from the Saqqaq culture, the first culture known to inhabit Greenland. On the basis of their DNA analysis, the authors identified the individual as a male. They also determined that, surprisingly, the geographical origin of the man was eastern Siberia, thereby providing insights into the peopling of the New World. Finally, the authors reconstructed some of the features and characteristics of this individual. We predict that many future studies will also combine methods for analysing ancient DNA with the scientific tools and genomic information that have accumulated as a result of the HGP. Such studies have the potential to reconstruct not only our genetic and geographical origins, but also what our ancestors looked like.

Gehiago irakurri nahi baduzu...

Expansion of the eukaryotic proteome by alternative splicing

2010-02-02T10:03:00.000+01:00

Insight

Nature 463, 457-463 (28 January 2010) | doi:10.1038/nature08909; Published online 27 January 2010, Review Article

Expansion of the eukaryotic proteome by alternative splicing

Timothy W. Nilsen & Brenton R. Graveley

Abstract

The collection of components required to carry out the intricate processes involved in generating and maintaining a living, breathing and, sometimes, thinking organism is staggeringly complex. Where do all of the parts come from? Early estimates stated that about 100,000 genes would be required to make up a mammal; however, the actual number is less than one-quarter of that, barely four times the number of genes in budding yeast. It is now clear that the 'missing' information is in large part provided by alternative splicing, the process by which multiple different functional messenger RNAs, and therefore proteins, can be synthesized from a single gene.

Alternative splicing of precursor messenger RNA (pre-mRNA) was first described almost 30 years ago, when it was discovered that membrane-bound and secreted antibodies are encoded by the same gene1, 2. Soon after, more examples of this phenomenon were described: for instance, the calcitonin/calcitonin-related polypeptide gene encodes two peptide hormones, which are expressed in a tissue-specific manner3. In both of these examples, the differential inclusion and exclusion of exonic sequences through alternative splicing (and alternative polyadenylation) is responsible for doubling the number of proteins encoded by the genes. Although it was at one time considered unusual, the estimated number of genes that encode more than one protein (or protein isoform) as a result of alternative splicing of a pre-mRNA has steadily risen over time. Recent studies using high-throughput sequencing indicate that 95–100% of human pre-mRNAs that contain sequence corresponding to more than one exon are processed to yield multiple mRNAs4, 5. And not only do most genes encode pre-mRNAs that are alternatively spliced, but also the number of mRNA isoforms encoded by a single gene can vary from two to several thousand. One spectacular example is the Drosophila melanogaster gene Down syndrome cell adhesion molecule (Dscam), which can generate 38,016 distinct mRNA isoforms6, a number far in excess of the total number of genes (~14,500) in the organism.
Gehiago irakurri nahi baduzu.....

Towards building a chromosome segregation machine

2010-02-02T09:57:00.000+01:00

Nature 463, 446-456 (28 January 2010) | doi:10.1038/nature08912; Published online 27 January 2010, Review Article

Towards building a chromosome segregation machine

Kerry Bloom & Ajit Joglekar

Abstract

All organisms, from bacteria to humans, face the daunting task of replicating, packaging and segregating up to two metres (about 6 × 109 base pairs) of DNA when each cell divides. This task is carried out up to a trillion times during the development of a human from a single fertilized cell. The strategy by which DNA is replicated is now well understood. But when it comes to packaging and segregating a genome, the mechanisms are only beginning to be understood and are often as variable as the organisms in which they are studied.

Chromosome segregation is challenging because the cell's packaging strategy needs to retain the organizational mechanisms that are responsible for delineating gene activity, as well as the higher-order spatial interactions that dictate the propensity of chromosomes to reside in specific domains (or territories). At the same time, chromosome segregation must be executed with high fidelity so that the mother cell and the daughter cell that arise from division receive precisely the same DNA content. The packaging machinery must distinguish sister chromatids from homologous chromosomes, while the segregation machinery must interpret intracellular spatial cues for coordinating chromosome segregation with cell division. Finally, the segregation machinery must function with far greater accuracy than man-made machines and with an exquisitely soft touch to prevent the DNA strands from breaking.

In eukaryotes, the mitotic spindle is responsible for chromosome segregation. This machine comprises dynamic microtubule polymers and forms between the opposite poles of a cell during mitosis. The polymers are constructed from tubulin subunits, which can be added or removed from either end of each polymer. During chromosome segregation, a coupling device, known as the kinetochore, is assembled at the centromere of each sister chromatid (that is, two kinetochores per chromosome), where it is poised to capture the fast-growing end (the plus end) of the microtubules in the mitotic spindle. In addition to this mechanical attachment, a signalling network that ensures the high fidelity of this process is assembled. This signalling network is sensitive to microtubule attachment and to force, presumably in the form of a change in protein structure and/or centromeric chromatin structure. Force can be sensed owing to the special geometry at the kinetochore, which is imparted by the cohesion of the sister chromatids. This geometry results from a DNA-strand-linkage system that is coupled to DNA replication, a system that allows the protein cohesin to link sister chromatids but not non-sister chromatids. When kinetochores form and capture microtubules in the mitotic spindle, the kinetochores of sister chromatids (the sister kinetochores) are attached to opposite spindle poles in the cell, and tension (force) is exerted across the sister chromatids, resulting in separation of the chromatids.
Gehiago irakurri nahi baduzu....

Egiturazko akatsak

2010-01-27T14:23:00.001+01:00

Inbertsioak eta meiosia

2010-01-27T14:21:00.001+01:00

Proteinen elektroforesia

2010-01-27T14:18:00.002+01:00

DNAren elektroforesia

2010-01-27T14:17:00.003+01:00

Translokazioak eta meiosia

2010-01-27T14:15:00.001+01:00

Meiosia

2010-01-27T14:14:00.001+01:00

PCR

2010-01-27T14:13:00.002+01:00

Diet and the evolution of human amylase gene copy number variation.

2010-01-25T11:08:00.000+01:00

Nat Genet. 2007 Oct;39(10):1256-60. Epub 2007 Sep 9.

Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, Werner J, Villanea FA, Mountain JL, Misra R, Carter NP, Lee C, Stone AC.
School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona 85287, USA.
Comment in:
* Nat Genet. 2007 Oct;39(10):1188-90.

Starch consumption is a prominent characteristic of agricultural societies and hunter-gatherers in arid environments. In contrast, rainforest and circum-arctic hunter-gatherers and some pastoralists consume much less starch. This behavioral variation raises the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis. We found that copy number of the salivary amylase gene (AMY1) is correlated positively with salivary amylase protein level and that individuals from populations with high-starch diets have, on average, more AMY1 copies than those with traditionally low-starch diets. Comparisons with other loci in a subset of these populations suggest that the extent of AMY1 copy number differentiation is highly unusual. This example of positive selection on a copy number-variable gene is, to our knowledge, one of the first discovered in the human genome. Higher AMY1 copy numbers and protein levels probably improve the digestion of starchy foods and may buffer against the fitness-reducing effects of intestinal disease.

Gehiago irakurri nahi baduzu....

Y kromosoma aldakorra

2010-01-20T09:51:00.000+01:00

Published online 13 January 2010 | Nature 463, 149 (2010) | doi:10.1038/463149a
News
The fickle Y chromosome

Chimp genome reveals rapid rate of change.

Lizzie Buchen

The male sex chromosome, long dismissed as the underachieving runt of the genome, has now been fully sequenced in a common chimpanzee. And comparison with its human counterpart — the only other Y chromosome to have been sequenced in such detail — reveals a rate of change that puts the rest of the genome to shame.

The common chimp (Pan troglodytes) and human Y chromosomes are "horrendously different from each other", says David Page of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, who led the work. "It looks like there's been a dramatic renovation or reinvention of the Y chromosome in the chimpanzee and human lineages."

Sex chromosomes evolved some 200 million–300 million years ago, but the chimpanzee and human lineages diverged only 6 million–7 million years ago. Comparisons of the chimp and human genomes suggested that not much has changed between the species since.

Gehiago irakurri nahi baduzu....

Hardy-Weinberg legearen azalpen polita

2010-01-13T10:40:00.001+01:00

Clinical pharmacology and pharmacogenetics in a genomics era: the DMET platform

2010-01-07T10:04:00.000+01:00

Pharmacogenomics

January 2010, Vol. 11, No. 1, Pages 89-103

Review

Clinical pharmacology and pharmacogenetics in a genomics era: the DMET platform

Tristan M Sissung‌¹, Bevin C English‌¹, David Venzon‌¹, William D Figg‌¹^† & John F Deeken‌²

†Author for correspondence

While no genome-wide pharmacogenetics study has yet been published, the field of pharmacogenetics is moving towards exploratory, large-scale analyses of the interaction between genetic variation and drug treatment. The Drug Metabolizing Enzymes and Transporters (DMET) platform offers a standardized set of 1936 variants in 225 genes related to drug absorption, distribution, metabolism and elimination that is useful to scan the genome for previously unknown associations between variation in absorption, distribution, metabolism and elimination genes and pharmacokinetic and pharmacodynamic outcomes of drug treatment. The purpose of this review is to put the DMET platform into context within the current study designs that have been used in pharmacogenetics, and to explore the role that DMET has played – and will play – in future pharmacogenetics studies.

Zutik

2010-01-07T09:51:00.002+01:00

2010-01-07 Argi Aldian /Berria

Mikel Iriondo - EHUko Antropologia irakaslea

Gizakia beste primateekin konparatzen dugunean zenbait ezaugarri bereizgarri datorkigu burura, hala nola gure burmuin handia, eskuekin gauzak manipulatzeko dugun trebezia edota lokomozio bipedoa. Azken honen eboluzioaren inguruan, hots, bi hanken gainean zutik ibiltzeko moduaren agerpenari dagokiolarik, literatura ugari idatzi dute ikerlariek Australopithecus-ak aurkitu zituztenetik hona. Australopithecus-ak, orain dela 2 eta 4 milioi urte tarteko gure arbaso bipedoak izan zirela gehienek onartzen dutela jakinda, eta sabana motako ingurune lehorrean bizi izan zirela jakinda, hipotesi ugari agertu ziren lokomozio mota berezi horren agerpenaren zioa azaltzeko: batzuentzat, belar artean zutik ibiltzeak belar gainetik ikusteko abantaila ematen omen zuen; beste batzuentzat, sabanan zehar garauak batzeko energetikoki eraginkorragoa omen zen zutik ibiltzea, paseo-abiadura mantenduz gero; bazeuden ere eskuak libre edukitzeko aukeran oinarritzen ziren ikerlariak. Hauen iritziz sakabanatuta zeuden zuhaitzen artean tresnak edo janaria eramateko egokiago omen zen bi hanken gainean ibiltzea. Horrela, XX. mendeko bigarren zatian zehar hipotesiak ugarituz joan ziren, betiere bipedia sabana motako ingurune batekin lotzen zutelarik.

2010-01-07T09:49:00.000+01:00

Nature 463, 39-40 (7 January 2010) | doi:10.1038/463039a; Published online 6 January 2010

Virology: Bornavirus enters the genome

Cédric Feschotte

A survey of mammalian genomes has unexpectedly unearthed DNA derived from bornaviruses, leading to speculation about the role of these viruses in causing mutations with evolutionary and medical consequences.

Some people might find it disquieting that a hefty 8% of human genetic material originates not from our vertebrate ancestors but from viruses. The assimilation of viral sequences into the host genome is a process referred to as endogenization. It occurs when viral DNA integrates into a chromosome of reproductive germline cells and is subsequently passed from parent to offspring. Until now, retroviruses were the only viruses known to generate such endogenous copies in vertebrates. But on page 84 of this issue, Horie et al.¹ report that non-retroviral viruses called bornaviruses have been endogenized repeatedly during mammalian evolution. The finding unveils bornaviruses as a potential cause of mutation and also as an unforeseen source of genomic innovation (Fig. 1).

Figure 1: Bornavirus in the genome, for better or worse.

a, Horie et al.¹ report that bornavirus gene sequences (red stars) became integrated into the germline of our ancestors, and through vertical transmission (by conventional inheritance) have become 'fixed' in the genome, thereby becoming endogenous viral insertions. A fixed viral insertion can follow one of two evolutionary fates: it can either decay into a pseudogene or be co-opted to form a new gene whose product has a cellular function. b, Circulating bornavirus sequences can become integrated into the genome of brain cells (the current target of Borna disease virus) after infection (exogenous insertion). These sequences are not heritable, but might cause mutations that interfere with brain function and may contribute to the development of psychiatric disorders.
High resolution image and legend (48K)

Gehiago irakurri nahi baduzu....

Jatorrizko artikulua

Artikulu interesgarri bat

2009-12-28T10:49:00.000+01:00

Nature 462, 1005-1010 (24 December 2009) | doi:10.1038/nature08645; Received 20 July 2009; Accepted 5 November 2009

Complex landscapes of somatic rearrangement in human breast cancer genomes

Philip J. Stephens¹, David J. McBride¹, Meng-Lay Lin¹, Ignacio Varela¹, Erin D. Pleasance¹, Jared T. Simpson¹, Lucy A. Stebbings¹, Catherine Leroy¹, Sarah Edkins¹, Laura J. Mudie¹, Chris D. Greenman¹, Mingming Jia¹, Calli Latimer¹, Jon W. Teague¹, King Wai Lau¹, John Burton¹, Michael A. Quail¹, Harold Swerdlow¹, Carol Churcher¹, Rachael Natrajan², Anieta M. Sieuwerts³, John W. M. Martens³, Daniel P. Silver⁴, Anita Langerød⁵, Hege E. G. Russnes⁵, John A. Foekens³, Jorge S. Reis-Filho², Laura van ’t Veer⁶, Andrea L. Richardson^4,⁷, Anne-Lise Børresen-Dale^5,⁸, Peter J. Campbell¹, P. Andrew Futreal¹ & Michael R. Stratton^1,⁹

Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Genetics, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway
The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands
Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Montebello, 0310 Oslo, Norway
Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.

Correspondence to: P. Andrew Futreal¹Michael R. Stratton^1,⁹ Correspondence and requests for materials should be addressed to M.R.S. (Email: mrs@sanger.ac.uk) or P.A.F. (Email: paf@sanger.ac.uk).

Top

Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.

Introduction

Cytogenetic studies over several decades have shown that somatic rearrangements, in particular chromosomal translocations, occur in many human cancer genomes^1,^2,³. The prevalence of rearrangements is, however, variable with some cancer genomes exhibiting few and others, including the genomes of many common adult epithelial cancers, showing many.

Somatic rearrangement is a common mechanism for the conversion of normal genes into cancer genes^1,^2,^3,^4,⁵. Indeed, of the ~400 genes that are currently known to be somatically mutated and implicated in cancer development, most are altered by genomic rearrangement (http://www.sanger.ac.uk/genetics/CGP/Census/). These rearrangements usually result in the formation of a fusion gene, derived from two disrupted normal genes, from which a fusion transcript and protein is generated. In some instances, however, rearrangements place an intact gene under the control of new regulatory elements or cause internal reorganization of a gene. These events usually result in activation of the protein to contribute to oncogenesis, as in the paradigm of the BCR–ABL fusion gene in chronic myeloid leukaemia⁶.

Gehiago irakurri nahi baduzu...

VIRUS OF THE YEAR 2009

2009-12-23T16:42:00.000+01:00

VIRUS OF THE YEAR:

The Novel H1N1 Influenza

Martin Enserink and Jon Cohen

For years, scientists have been warning about the potentialfor an influenza pandemic on the order of the 1918 Spanish flu.But the pandemic that erupted last spring looks nothing likethe one health officials have been preparing to combat.

WEB LINKS

Find more information and resources at Science's H1N1 flu page.

For years, scientists have been warning that an influenza pandemiccould strike at any moment, triggering a global catastropheon the order of the 1918 Spanish flu. They imagined the culpritwould surface in Asia—and, since 2003, have worried thatthe avian influenza strain H5N1 might be it. Health officialsworldwide drafted one preparedness plan after another.

But the pandemic that erupted last spring looks nothing likethe one in the plans. Not only did it begin in North America,but the swine virus behind it is a novel form of an H1N1 strainalready circulating in humans. And although the new H1N1 isunusually dangerous for the young and for pregnant women, inmost otherwise healthy people it causes a disease no more severethan seasonal flu. Scientists have repeatedly warned that thisrelatively mild virus could mutate or swap genes with cousinsand become deadlier. But for now, it looks as if this H1N1,which mysteriously jumped from swine to humans, will go downin history more for causing confusion than catastrophe.

Breakthrough of the Year

2009-12-23T16:40:00.000+01:00

Video: Ardipithecus ramidus

A video introduction to the year's top science story, featuringscientists C. Owen Lovejoy, Tim White, Giday WoldeGabriel, YohannesHaile-Selassie, Sciencecontributing correspondent Ann Gibbons,and commentary by paleoanthropologist Andrew Hill.

Umorea eta genetika

2009-12-08T18:28:00.001+01:00

Twin Res. 2000 Mar;3(1):17-22.

Happy families: a twin study of humour .

Cherkas L, Hochberg F, MacGregor AJ, Snieder H, Spector TD.

Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, London, UK.

The objective of this study was to estimate how much of an individual's appreciation of humour is influenced by genetic factors, the shared environment or the individual's unique environment. A population-based classical twin study of 127 pairs of female twins (71 monozygous (MZ) and 56 dizygous (DZ) pairs) aged 20-75 from the St Thomas' UK Adult Twin Registry elicited responses to five 'Far Side' Larson cartoons on a scale of 0-10. Within both MZ and DZ twin pairs, the tetrachoric correlations of responses to all five cartoons were significantly greater than zero. Furthermore, the correlations for MZ and DZ twins were of similar magnitude and in some cases the DZ correlation was greater than that of the MZ twins. This pattern of correlations suggests that shared environment rather then genetic effects contributes to cartoon appreciation. Multivariate model-fitting confirmed that these data were best explained by a model that allowed for the contribution of the shared environment and random environmental factors, but not genetic effects. However, there did not appear to be a general humour factor underlying responses to all five cartoons and no effect of age was seen. The shared environment, rather than genetic factors, explains the familial aggregation of humour appreciation as assessed by the specific 'off the wall' cognitive type of cartoons used in this study.

Quino eta klonazioa

2009-12-04T15:05:00.002+01:00

Aldaketa baten garrantzia

2009-11-25T11:16:00.001+01:00

Nature 428, 373-374 (25 March 2004) | doi:10.1038/428373a

Human genetics: Muscling in on hominid evolution

Pete Currie¹

Top of page

A molecular difference in the jaw muscles of human and non-human primates has tantalizing echoes in the fossil record. Was this divergence a central event in the evolution of the skull of modern hominids?

Ever since Bishop Wilberforce famously ridiculed the possibility that man was descended from apes, and T. H. Huxley bravely chose primate ancestry rather than ignorance, the debate over our origins has claimed a special place in evolutionary theory. With the acceptance by most of us that we are indeed a product of natural selection, discussions surrounding the issue have cooled somewhat. But exactly how natural selection acted to produce the modern human form has remained hotly contested.

In the history of this debate, the paper by Stedman et al. on page 415 of this issue¹ is of special significance. It describes what may be the first functional genetic difference between humans and apes (Fig. 1). Remarkably, the timing of the appearance of this genetic alteration, or mutation, roughly coincides with the appearance of 'human-like' characteristics in the hominid fossil record, and the authors present convincing arguments as to how the mutation could have been responsible for their acquisition.

Figure 1: News of chews — the jaw muscles of apes, such as this mountain gorilla, and humans could reflect a profound evolutionary divergence.

High resolution image and legend (133K)

Gehiago irakurri nahi baduzu...

Artikulua irakurri nahi baduzu....

Iñaki Ugarteburu gure orimenean

2009-11-25T11:08:00.001+01:00

Gutxi esan daiteke, goian bego.

Iñaki Ugarteburu

Publish at Calaméo or browse others.

Eboluzioa

2009-11-23T10:49:00.000+01:00

Nature 461, 1243-1247 (29 October 2009) | doi:10.1038/nature08480; Received 9 July 2009; Accepted 28 August 2009; Published online 18 October 2009; Corrected 29 October 2009

Genome evolution and adaptation in a long-term experiment with Escherichia coli

Jeffrey E. Barrick^1,⁷, Dong Su Yu^2,^3,⁷, Sung Ho Yoon², Haeyoung Jeong², Tae Kwang Oh^2,⁴, Dominique Schneider⁵, Richard E. Lenski¹ & Jihyun F. Kim^2,⁶

Top

The relationship between rates of genomic evolution and organismal adaptation remains uncertain, despite considerable interest. The feasibility of obtaining genome sequences from experimentally evolving populations offers the opportunity to investigate this relationship with new precision. Here we sequence genomes sampled through 40,000 generations from a laboratory population of Escherichia coli. Although adaptation decelerated sharply, genomic evolution was nearly constant for 20,000 generations. Such clock-like regularity is usually viewed as the signature of neutral evolution, but several lines of evidence indicate that almost all of these mutations were beneficial. This same population later evolved an elevated mutation rate and accumulated hundreds of additional mutations dominated by a neutral signature. Thus, the coupling between genomic and adaptive evolution is complex and can be counterintuitive even in a constant environment. In particular, beneficial substitutions were surprisingly uniform over time, whereas neutral substitutions were highly variable.

Gehiago irakurri nahi baduzue...

Artikulu interesgarri bat

2009-11-19T13:55:00.001+01:00

Nature 462, 296-297 (19 November 2009) | doi:10.1038/462296a; Published online 18 November 2009

Epigenomics: Methylation matters

Dirk Schübeler¹

Genome-wide maps of methylated cytosine bases at single-base-pair resolution in human cells reveal distinct differences between cell types. These maps provide a starting point to decode the function of this enigmatic mark.

Methylated cytosine, often referred to as DNA's fifth base, makes up a subset of nucleotides in the mammalian genome. As cytosine methylation does not affect base pairing, deposition of this mark can regulate processes, such as transcription, without affecting the genetic blueprint. Once established, the methylated cytosine modification can be faithfully copied to newly synthesized DNA, and so can be passed on to daughter cells, making it a true epigenetic mark. Many groups have studied the genomic distribution of DNA cytosine methylation and other chemical modifications of histone proteins to describe what has been dubbed the epigenome. On page 315et al.¹ — provide the first complete DNA-methylation map of the human genome at single-base-pair resolution. Their accomplishment reveals intriguing features of the methylcytosine mark that were not identified in previous, less-comprehensive maps^2,³. of this issue, a team headed by Joseph Ecker — Lister

Gehigo irakurri nahi baduzu

Selective sequencing solves a genetic mystery

2009-11-16T09:50:00.003+01:00

Published online 13 November 2009 | Nature | doi:10.1038/news.2009.1085

News Examining only protein-coding genes finds cause of Miller syndrome.

Elie Dolgin

Targeted sequencing of the entire protein-coding portion of the human genome has for the first time discovered the cause of a rare genetic disorder.

Sequencing just exons could efficiently identify the genes responsible for some diseases.Ingram Publishing

"This technology is incredibly promising," says James Kiley, director of the division of lung diseases at the National Heart, Lung and Blood Institute in Bethesda, Maryland, which partly funded the work. "It's giving us a more efficient way to identify the causal genetic factors of disease."

Protein-coding genes make up only about 1% of the human genome, but they harbour the bulk of the mutations that contribute the most to disease. So, rather than sequencing entire genomes, many researchers are starting to decode only the protein-coding exons — collectively called the 'exome' — to make genetic inferences at a fraction of the cost of whole-genome sequencing.

Gehiago jakin nahi baduzu....

Programa interesgarri bat

2009-11-16T09:32:00.003+01:00

Atzo la2-ean geneen inguruan programa interesgarri bat eman zuten . Lopez Otin ikerlariari elkarrizketa bat egin zioten, ea zer iruditzen zaizuen.

Tres 14

Genes.

Emitido: 15/11/2009 [ 26 : 52 "]

Hizkuntzaren genea

2009-11-12T12:10:00.000+01:00

Published online 11 November 2009 | Nature | doi:10.1038/news.2009.1079

Evolution of a single gene linked to language

Mutations in the FOXP2 gene could help explain why humans can speak but chimps can't.

Kerri Smith

Published online 11 November 2009 | Nature | doi:10.1038/news.2009.1079

Changes to the sequence of one gene may help to explain why humans talk but chimps don't.mlorenzphotography/ Getty

Two tiny changes in the sequence of one gene could have helped install the mechanisms of speech and language in humans.

In 2001, a gene calledFOXP2 was found to underlie a rare inherited speech and language disorder¹. It encodes a transcription factor called FOXP2, a protein 'dimmer-switch' that binds to DNA and helps to determine to what extent other genes are expressed as proteins.

Experiments have now revealed that the human version of FOXP2, which has two different amino acids compared with the version carried by chimps, has differing effects on genes in the brains of the two species. These differences could affect how the brain develops, and so explain why only humans are capable of language.

To find out whether these changes in FOXP2 had a biological function, a team led by Daniel Geschwind of the University of California, Los Angeles, inserted the two versions into human brain cells and looked at expression of the genes that the protein regulates. They found that the human version increased the expression of 61 genes and decreased the expression of 51 genes compared with the chimp version of the protein. To double-check that the same was happening in real brains, they looked at the expression of these genes in human and chimp brain tissue and found similar expression levels as in the cells. Their study is published in Nature².

Gehigo irakurri nahi baduzu

Iluntasunean argia

2009-11-12T10:06:00.001+01:00

Argi Aldian, Berria

ASIER FULLAONDO - EHUKO GENETIKA IRAKASLEA

Orain dela gutxi Euskal Herriko Unibertsitatean izandako hitzaldi batera, jatorriz euskalduna, jaiotzez kubatarra eta bizi eta ikerketa AEB egiten zuen irakasle bat etorri zen. Gustavo Aguirre zuen izena, eta bere bizitzan egindako ikerketari buruz jardun zuen. Hitzaldiaren titulu laburtua Genetik terapia genikora zen, eta Leber's Congenital Amaurosis (LCA) gaixotasuna hizpide hartu zuen hitzaldian. Gaixotasun hori itsutasun mota bat da: jaiotzetik pertsona horiek gaixotasuna dute, baina denek ez dute sintomatologia bera agertzen; hau da, itsutasunaren garapena ez da homogeneoa. LCA gaixotasunean 2 azpi mota bereiz daitezke, bata pertsona nagusietan garatzen dena; pertsona horiek, denbora aurrera joan ahala, ikusmena galtzen dute itsu bihurtu arte. Eta bigarren mota haurretan agertzen da: umeak jaiotzetik itsuak dira, edo ikusmenaren galera oso azkarra dute. LCA gaixotasuna genetikoa da, eta haren sorreran hainbat genek parte hartzen dutela aspaldi jakina da. LCA sortzen zuen geneetariko bat Aguirreren taldeak aurkitu zuen, RPE65 genea. Haren ikerketek ere argitu zuten gaixotasunaren zergatia. Zergatia ezagutu ondoren hurrengo erronka gaixotasun hau osatzea zen, eta horretarako terapia genikoan pentsatu zuten.

Gehigo irakurri nahi baduzu....

Lamarck berpiztu da?

2009-11-11T11:24:00.000+01:00

Nature 447, 396-398 (24 May 2007) | doi:10.1038/nature05913; Published online 23 May 2007

IntroductionPerceptions of epigenetics

Adrian Bird¹

Geneticists study the gene; however, for epigeneticists, there is no obvious 'epigene'. Nevertheless, during the past year, more than 2,500 articles, numerous scientific meetings and a new journal were devoted to the subject of epigenetics. It encompasses some of the most exciting contemporary biology and is portrayed by the popular press as a revolutionary new science — an antidote to the idea that we are hard-wired by our genes. So what is epigenetics?

There has always been a place in biology for words that have different meanings for different people. Epigenetics is an extreme case, because it has several meanings with independent roots. To Conrad Waddington, it was the study of epigenesis: that is, how genotypes give rise to phenotypes during development¹. By contrast, Arthur Riggs and colleagues defined epigenetics as "the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence"²: in other words, inheritance, but not as we know it. These definitions differ markedly, although they are often conflated as though they refer to a single phenomenon. Waddington's term encompasses the activity of all developmental biologists who study how gene activity during development causes the phenotype to emerge, but it suffers from the disadvantage that developmental biologists themselves rarely, if ever, use this word to describe their field. In this sense, the usage is obsolete. The definition put forward by Riggs and colleagues tells us what epigenetics is not (inheritance of mutational changes), leaving open what kinds of mechanism are at work. In this article, I give examples of how epigenetic phenomena are studied and interpreted, and I propose a revised definition that embodies contemporary usage of the word.

The molecular basis of heritable epigenetics has been studied in a variety of organisms. The DNA methylation system and the Polycomb/Trithorax systems come closest to the ideal, because alterations in these systems are often inherited by subsequent generations of cells and sometimes organisms (Box 1). A classic case of what Robin Holliday named epimutation³ is the peloric variant of toadflax (Linaria) flowers (Fig. 1), first described by Linnaeus. In this variant, heritable silencing of the gene Lcyc, which controls flower symmetry, is due not to a conventional mutation (that is, a mutation in the nucleotide sequence) but to the stable transmission of DNA methylation at this locus from generation to generation⁴. Although most variants arising in laboratory plants are due to conventional mutations rather than epimutations of this kind, examples of transgenerational epigenetics are now well documented in plants (see page 418) and fungi. In animals, however, the transmission of epigenetic traits between organismal generations has, so far, been detectable only by using highly sensitive genetic assays⁵. The mouse agouti locus (also known as nonagouti), which affects coat colour, is the best-studied example, being affected by the extent of DNA methylation at an upstream transposon. Genetically identical parents whose agouti genes are in different epigenetic states tend to produce offspring with different coat colours, although the effect is variable.

Gehigo irakurri nahi baduzu.....

Lamarck berpiztu da?

2009-11-11T11:16:00.001+01:00

Nature Neuroscience
Published online: 8 November 2009 | doi:10.1038/nn.2436

Dynamic DNA methylation programs persistent adverse effects of early-life stress

Chris Murgatroyd¹, Alexandre V Patchev¹, Yonghe Wu¹, Vincenzo Micale¹, Yvonne Bockmühl¹, Dieter Fischer¹, Florian Holsboer¹, Carsten T Wotjak¹, Osborne F X Almeida¹ & Dietmar Spengler¹

Adverse early life events can induce long-lasting changes in physiology and behavior. We found that early-life stress (ELS) in mice caused enduring hypersecretion of corticosterone and alterations in passive stress coping and memory. This phenotype was accompanied by a persistent increase in arginine vasopressin (AVP) expression in neurons of the hypothalamic paraventricular nucleus and was reversed by an AVP receptor antagonist. Altered Avp expression was associated with sustained DNA hypomethylation of an important regulatory region that resisted age-related drifts in methylation and centered on those CpG residues that serve as DNA-binding sites for the methyl CpG–binding protein 2 (MeCP2). We found that neuronal activity controlled the ability of MeCP2 to regulate activity-dependent transcription of the Avp gene and induced epigenetic marking. Thus, ELS can dynamically control DNA methylation in postmitotic neurons to generate stable changes in Avp expression that trigger neuroendocrine and behavioral alterations that are frequent features in depression.

“Avances en Medicina Genómica” IV Conferencia Anual

2009-11-10T10:00:00.001+01:00

Estimado/a Sr(a):

Le escribo este correo para informarle sobre la IV Conferencia Anual EuroEspes, organizada por la Fundación EuroEspes, y que se celebrará en Bergondo, La Coruña, el próximo 19 de diciembre de 2.009, bajo el título: “Avances en Medicina Genómica”.

La Fundación EuroEspes, una organización sin ánimo de lucro que tiene como objetivos fundacionales la promoción cultural, científica y sanitaria, el fortalecimiento institucional, la cooperación para el desarrollo y la investigación científica y el desarrollo tecnológico, organiza este evento, que ha sido reconocido de interés sanitario por la Consellería de Sanidade de la Xunta de Galicia.

La Universidad Camilo José Cela (Madrid) y otras Universidades seleccionadas concederán créditos universitarios por la asistencia a la Conferencia (para más información escriba a secretariat@fundacioneuroespes.org).

El objetivo de este evento es promocionar programas educativos para fomentar la utilización de la Farmacogenética y la Farmacogenómica como procedimientos estándar en el sector sanitario con el fin de implantar una medicina personalizada.

Como verá en el programa, hablarán expertos en diferentes aspectos de este innovador campo médico, en unas sesiones que prometen ser del máximo interés.

Esperamos que Ud. valore la importancia que tiene este acto, no sólo en su entorno inmediato sino a nivel mundial, y que vea también los beneficios que se pueden obtener asistiendo a esta cuarta edición.

Podrá encontrar toda la información que necesite en la página Web de la Conferencia: www.euroespesannualconference.org.

Nos encantaría darle la bienvenida a La Coruña el próximo mes de diciembre.

Saludos cordiales,

Adam McKay
Secretario del Prof. Ramón Cacabelos, M.D., Ph.D., D.M.Sc. (Presidente de la Fundación EuroEspes)

Nork esan zuen genomen sekuentziazioa ez zela garrantzitsua?

2009-11-05T15:10:00.004+01:00

10,000 genomes to come

Vertebrates in line for massive sequencing project.

Erika Check Hayden

Published online 4 November 2009 | Nature 462, 21 (2009) | doi:10.1038/462021a

The anteater could have its genome sequenced.A. SHAH/NATUREPL.COM

Results are just beginning to arrive for the 1000 Genomes Project, a genomic study of human diversity. However, an international group is already planning something even more ambitious — a 10,000 genomes project. The initiative, called Genome 10K, aims to tackle thousands of vertebrate species.

Project members write this week in the Journal of Heredity that the effort will provide an unprecedented look at the genomic mechanisms for generating diversity in a group of animals with different lifestyles and adaptations.

"We see this stunning diversity of forms in vertebrates, from manatees to anteaters," says David Haussler of the University of California, Santa Cruz, one of the three masterminds behind the project, which involves 68 scientists from five continents. "What continually strikes me is the unbelievable malleability and adaptability of the vertebrate genome," he says, "and we have an enormous amount to learn about the genetic roots of that."

Gehiago jakin nahi baduzu.......

Gene Therapy Helps Blind Children See

2009-11-02T09:35:00.002+01:00

Bioforoko hitzaldian ikusi genuena errealitate bihurtuta. (jatorrizko orrian bi bideo interesgarri daude)

Gene Therapy Helps Blind Children See

By Jocelyn Kaiser
ScienceNOW Daily News
24 October 2009

A single injection of DNA into the eyes of four children born with a blindness-causing disease has given them enough vision to walk without help. The study, published today, confirms that if patients with this disease are given gene therapy early in life, the results can be dramatic.
Several clinical trials in the United States and Europe have been using gene therapy to treat a disease called Leber's congenital amaurosis (LCA), which affects about 3000 people in the United States. Those born with LCA start losing their sight at birth and are completely blind by age 40. Children born with one form, LCA2, have defects in a gene called RPE65 that helps the retina's light-sensing cells make rhodopsin, a pigment needed to absorb light. Without rhodopsin, the photoreceptor cells gradually die. In 2001, researchers at the University of Pennsylvania (Penn) showed that they could partially restore sight to blind dogs with this defect by injecting a good copy of RPE65 into their eyes.

Two years ago, the Penn team began a small safety study of the therapy in humans with collaborators at the Children's Hospital of Philadelphia. They injected each patient's worse eye with a modified virus carrying the RPE65 gene. Early results from this trial and a similar study in the United Kingdom published in April 2008 showed that four of six young adults with LCA2 who received the treatment could later sense more light and perform better in an obstacle course.

But the Penn researchers knew from their studies in animals that children should improve even more because they have more intact retinal tissue than adults do. Today in an online paper in The Lancet, their team and collaborators in Europe report full study results for three of the adults they treated earlier and nine more patients, including four children ages 8 to 11. The children gained more light sensitivity than the adults did--their light sensitivity increased as much as four orders of magnitude, versus one--and they made far fewer mistakes in an obstacle course.

One patient, Corey Haas, appears in a video 3 months after the treatment breezing through the obstacle course, following arrows and avoiding objects that he cannot see with his treated eye covered. Corey, 9, told reporters at a press conference this week that for the first time he can recognize faces, play baseball, read large print books, and ride his bike around his neighborhood alone. "It has helped him tremendously," said his father, Ethan Haas.
The LCA2 trials are a rare success for the field of gene therapy, which has also cured children with the immune disorder known as bubble boy disease. And they should pave the way for treating more vision disorders. "It's an incredible launching pad to be able to target other diseases," says Penn gene therapy researcher Jean Bennett, who led the study.
Showing that the LCA2 gene therapy treatment works best in children is "a big step" for inherited blindness, says geneticist Frans Cremers of Radboud University Nijmegen Medical Center in the Netherlands, who wrote an accompanying commentary in The Lancet. He notes that eight other vision diseases, including retinitis pigmentosa, have now been treated in mice and are ready to be tested in people. The challenge, he says, will be to expand genetic testing of people with blindness so as to find enough eligible patients for clinical trials of these rare disorders.

Urte honetako nobel saridun baten hitzaldi interesgarri bat

2009-10-27T10:59:00.003+01:00

Elizabeth Blackburn, June 2008
University of California, San Francisco/Department of Biochemistry and Biophysics

Part 1: The Roles of Telomeres and Telomerase (48:27)

Part 2: Telomeres and Telomerase in Human Stem Cells and in Cancer (26:58)

Part 3: Stress, Telomeres and Telomerase in Humans (45:58)

Artikulu interesgarri bat

2009-10-15T10:33:00.000+02:00

Nature 461, 891-892 (15 October 2009) | doi:10.1038/461891a; Published online 14 October 2009

Stem cells: A fateful age gap

Tim Stearns¹

When a stem cell divides, one sister cell differentiates and the other retains its stem-cell identity. Differences in the age of an organelle — the centriole — inherited at cell division may determine these differing fates.

One of the enduring mysteries of biology is how two genetically identical sister cells become different from each other after cell division. Stem cells are particularly interesting in this respect because they can divide so that one of the two resulting cells remains an undifferentiated stem cell while the other becomes a differentiated cell type. It has long been thought that such asymmetric cell division may reflect an underlying asymmetry in the segregation of a cellular component at division; the asymmetrically inherited component would have properties that allow it to control the fate of its recipient cell. In this issue (page 947), Wang et al.¹ present evidence that the centrosome, a multifunctional organelle that is common to all animal cells, might be such a determinant.

Gehiago irakurri nahi baduzu

Artikulu interesgarri bat

2009-10-15T10:22:00.001+02:00

Science 9 October 2009:
Vol. 326. no. 5950, pp. 289 - 293
DOI: 10.1126/science.1181369

Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome

Erez Lieberman-Aiden,¹^,2^,3^,4^,* Nynke L. van Berkum,⁵^,* Louise Williams,¹ Maxim Imakaev,² Tobias Ragoczy,⁶^,7 Agnes Telling,⁶^,7 Ido Amit,¹ Bryan R. Lajoie,⁵ Peter J. Sabo,⁸ Michael O. Dorschner,⁸ Richard Sandstrom,⁸ Bradley Bernstein,¹^,9 M. A. Bender,¹⁰ Mark Groudine,⁶^,7 Andreas Gnirke,¹ John Stamatoyannopoulos,⁸ Leonid A. Mirny,²^,11 Eric S. Lander,¹^,12^,13^, Job Dekker⁵^,

We describe Hi-C, a method that probes the three-dimensionalarchitecture of whole genomes by coupling proximity-based ligationwith massively parallel sequencing. We constructed spatial proximitymaps of the human genome with Hi-C at a resolution of 1 megabase.These maps confirm the presence of chromosome territories andthe spatial proximity of small, gene-rich chromosomes. We identifiedan additional level of genome organization that is characterizedby the spatial segregation of open and closed chromatin to formtwo genome-wide compartments. At the megabase scale, the chromatinconformation is consistent with a fractal globule, a knot-free,polymer conformation that enables maximally dense packing whilepreserving the ability to easily fold and unfold any genomiclocus. The fractal globule is distinct from the more commonlyused globular equilibrium model. Our results demonstrate thepower of Hi-C to map the dynamic conformations of whole genomes.

¹ Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), MA 02139, USA.
² Division of Health Sciences and Technology, MIT, Cambridge, MA 02139, USA.
³ Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, MA 02138, USA.
⁴ Department of Applied Mathematics, Harvard University, Cambridge, MA 02138, USA.
⁵ Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁶ Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁷ Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA.
⁸ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
⁹ Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
¹¹ Department of Physics, MIT, Cambridge, MA 02139, USA.
¹² Department of Biology, MIT, Cambridge, MA 02139, USA.
¹³ Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

Horoskopo genetikoak

2009-10-15T09:34:00.002+02:00

Argi Aldian 2009-10-15

BEGOÑA JUGO. - EHUKO GENETIKA IRAKASLEA

Horoskopo genetikoak

Lankide bat oso arduratuta dago, aurrerapen teknologikoen garai honetan oinarri zientifikorik gabeko sinismenek eta aieruzko usteek gero eta jarraotzaile gehiago dituztelako. Eta berak eguraldiaren iragarpena aipatzen du adibide gisa, baina gure osasunarekin erlazionatutako beste gai batzuetan ere aplikagarria da joera hori.

Gehiago irakurri nahi baduzu

Txaskarrillo

2009-10-09T10:27:00.003+02:00

Genotype Analysis Identifies the Cause of the "Royal Disease"

Evgeny I. Rogaev , Anastasia P. Grigorenko , Gulnaz Faskhutdinova , Ellen L. W. Kittler ³, Yuri K. Moliaka

The "royal disease," a blood disorder transmitted from QueenVictoria to European royal families, is a striking example ofX-linked recessive inheritance. Although the disease is widelyrecognized to be a form of the blood-clotting disorder hemophilia,its molecular basis has never been identified, and the royaldisease is now extinct. We identified the likely disease-causingmutation by applying genomic methodologies (multiplex targetamplification and massively parallel sequencing) to historicalspecimens from the Romanov branch of the royal family. The mutationoccurs in F9, a gene on the X chromosome that encodes bloodcoagulation Factor IX, and is predicted to alter RNA splicingand lead to production of a truncated form of Factor IX. Thus,the royal disease is the severe form of hemophilia, also knownas hemophilia B or Christmas disease.

2009ko nobel saria

2009-10-08T14:46:00.001+02:00

The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine 2009 jointly to

Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak

for the discovery of

"how chromosomes are protected by telomeres and the enzyme telomerase"

Summary

This year's Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.

Gehiago irakurri nahi baduzu...

Genetika eta bihotzeko arazoak

2009-10-07T11:28:00.002+02:00

Hitzaldi honetan genetika eta bihotzeko arazoen arteko erlazioa oso modu argian azaltzen da

UCSF's Osher Lifelong Learning Institute presents Dr. Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease. Dr. Srivastava discusses the genetics of heart disease. Series: "UCSF M..

Genetika eta medikuntza

2009-10-05T10:46:00.003+02:00

Nahiz eta gure medikuntza fakultatean genetikari ez zaion beharrezko garrantzia ematen hemen daukazue "University of California Television" kanalean agertzen den aurkezpen interesgarri bat.

A New Era in Medicine: Genetics

From: UCtelevision | 25 de enero de 2008 | 2901 reproducciones

Katherine Hyland explores the knowledge that is resulting from increasing genetic understanding. This presentation is part of the course, Basic Principles Underlying Modern Medicine, which mirrors the first block of coursework included in the Essential Core of the UCSF Medical School curriculum. Series: "UCSF Mini Medical School for the Public" [7/2007] [Health and Medicine] [Show ID: 12250]

DNA-ren erauzketa

2009-10-05T10:33:00.000+02:00

Bideo honetan ikus dezakegu DNA nola erauzi daitekeen.

Sexuaren finkapena

2009-10-05T10:12:00.002+02:00

Semeneya korrikalariak uda honetan garapen sexualaren eta sexuaren finkapenaren inguruko auzia martxan jarri du. Bideo honetan sexuaren finkapenearen inguruko oinarrizko informazioa azaltzen da.

EHUSFERA

2009-09-17T14:31:00.002+02:00

Kaixo Ehusfera martxan dago eta bertan izango dugu gure bloga hemendik aurrera.
http://www.ehu.es/ehusfera/genetikamedikuntza

Glosategia

2009-09-16T09:36:00.002+02:00

Ondoko helbidean genetika terminoen glosategi bat dago, gehiago ikasi aukera sakatuz informazio gehiago agertzen da, informazio grafikoa.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=glossary

Kontseilu genetikoaren ondorioak.......

2009-07-16T12:57:00.001+02:00

No Risk in Disclosing Genetic Risks

By Michael Torrice
ScienceNOW Daily News
15 July 2009

Sitting in your doctor's office, you get the bad news: Thanks to a faulty gene, you're 15 times more likely than the average person to develop Alzheimer's disease (AD). But despite the diagnosis, you're unlikely to become more anxious or depressed within the next year, according to a new study.

In this age of relatively easy genome sequencing, anyone can send their saliva to a company and learn their risk of developing a variety of genetic diseases. But is this a good thing? Researchers and bioethicists worry that bad news could traumatize patients and cause depression or other psychological harm (Science, 22 February 2008, p. 1022). Few studies, however, have investigated the psychological effects of finding out this information................

Translokazioak

2009-07-09T12:38:00.001+02:00

Translocations

Translocations are chromosomal abnormalities which occur when chromosomes break and the fragments rejoin to other chromosomes. There are many structurally different types of translocations, some of which are discussed below. As with inversions, there is no loss of genetic material, although the breakpoint can cause disruption of a critical gene or juxtapose pieces of two genes to create a fusion gene that induces cancer. In general however, the problem with translocations occurs during meiosis and is manifest as reductions in fertility.

Artikulu interesgarri bat

2009-07-08T10:50:00.000+02:00

Nature advance online publication 1 July 2009 | doi:10.1038/nature08161; Received 10 March 2009; Accepted 19 May 2009; Published online 1 July 2009

Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation

Sundeep Kalantry^1,^2,³, Sonya Purushothaman^1,^2,³, Randall Bryant Bowen^1,^2,³, Joshua Starmer^1,^2,³ & Terry Magnuson^1,^2,³

Department of Genetics,
Carolina Center for Genome Sciences,
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA

Correspondence to: Terry Magnuson^1,^2,³ Correspondence and requests for materials should be addressed to T.M. (Email: trm4@med.unc.edu).

XX female mammals undergo transcriptional silencing of most genes on one of their two X chromosomes to equalize X-linked gene dosage with XY males in a process referred to as X-chromosome inactivation (XCI). XCI is an example of epigenetic regulation¹. Once enacted in individual cells of the early female embryo, XCI is stably transmitted such that most descendant cells maintain silencing of that X chromosome². In eutherian mammals, XCI is thought to be triggered by the expression of the non-coding Xist RNA from the future inactive X chromosome (Xi)^3,^4,⁵; Xist RNA in turn is proposed to recruit protein complexes that bring about heterochromatinization of the Xi^6,⁷. Here we test whether imprinted XCI, which results in preferential inactivation of the paternal X chromosome (Xp), occurs in mouse embryos inheriting an Xp lacking Xist. We find that silencing of Xp-linked genes can initiate in the absence of paternal Xist; Xist is, however, required to stabilize silencing along the Xp. Xp-linked gene silencing associated with mouse imprinted XCI, therefore, can initiate in the embryo independently of Xist RNA.

Kariotipoak nola egin ikasteko tresna

2009-07-08T10:08:00.001+02:00

Esteka honetan daukazue kariotipoak egiteko tresnatxo bat.

http://www.unav.es/genetica/KY/Ejercicio1.html

Zer da FISH

2009-07-06T10:14:00.002+02:00

Fluorescent in situ hybridization

FISH (fluorescence in situ hybridization) is a cytogenetic technique used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH uses fluorescent probes that bind to only those parts of the chromosome with which they show a high degree of sequence similarity. Fluorescence microscopy can be used to find out where the fluorescent probe bound to the chromosomes. FISH is often used for finding specific features in DNA for use in genetic counseling, medicine, and species identification. FISH can also be used to detect and localize specific mRNAs within tissue samples. In this context, it can help define the spatial-temporal patterns of gene expression within cells and tissues.

Zer da Onkogenea?

2009-07-02T15:36:00.001+02:00

Oncogene

From Wikipedia, the free encyclopedia

An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a cancer cell.^[1]

Many cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead.^[2] Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target those DNA sequences and their products.^[3]^[4]^[5]^[6]

Publicar entrada

Zer dira mikrosateliteak?

2009-07-02T15:31:00.001+02:00

From Wikipedia, the free encyclopedia

MICROSATELLITE

Microsatellites, or Simple Sequence Repeats (SSRs), are polymorphic loci present in nuclear and organellar DNA that consist of repeating units of 1-6 base pairs in length. ^[1] They are typically neutral, co-dominant and are used as molecular markers which have wide-ranging applications in the field of genetics, including kinship and population studies. Microsatellites can also be used to study gene dosage (looking for duplications or deletions of a particular genetic region).

Hitzaldi interesgarri bta

2009-06-29T11:08:00.001+02:00

Sarah Tishkoff - "Human Origins in Africa" at Engaging

Sarah Tishkoff is the David and Lyn Silfen University Associate Professor in Genetics and Biology at the University of Pennsylvania. A leading global expert in human genetics, Dr. Tishkoff works pr...

Artikulu interesgarri bat

2009-06-24T16:04:00.001+02:00

Nature Genetics 41, 393 - 395 (2009)
Published online: 15 March 2009 | doi:10.1038/ng.363

Human mutation rate associated with DNA replication timing

John A Stamatoyannopoulos^1,⁴, Ivan Adzhubei^2,⁴, Robert E Thurman¹, Gregory V Kryukov², Sergei M Mirkin³ & Shamil R Sunyaev²

Eukaryotic DNA replication is highly stratified, with different genomic regions shown to replicate at characteristic times during S phase. Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. This correlation between mutation rate and regionally stratified replication timing may have substantial evolutionary implications.

Nukleotido bakarreko polimorfismoak bereizteko mikroarraiak

2009-06-24T15:10:00.003+02:00

Artikulu interesgarri bat

2009-06-17T13:14:00.003+02:00

Published online 15 April 2009 | Nature 458, 826-829 (2009) | doi:10.1038/458826a

Developmental biology: Two by two

Could genes explain the remarkable rate of identical twins born in some remote villages around the world? David Cyranoski investigates a long-standing biological curiosity.

http://www.nature.com/news/2009/090415/full/458826a.html

Artikulu interesgarri bat

2009-06-17T13:09:00.002+02:00

Why people with Down's syndrome get fewer cancers

Extra gene cuts growth of blood vessels that feed tumours.

Anjali Nayar

People with Down's syndrome have extra genes that slow tumour growth.Punchstock

A gene on the extra chromosome that causes Down's syndrome helps to protect those with the disorder from some types of cancer.

Sandra Ryeom, a vascular biologist at Children's Hospital Boston in Massachusetts, and her colleagues experimented with mice and with human cells to show that an additional third copy of the DSCR1 gene (also known as RCAN1) can suppress the growth of the blood vessels that feed cancerous tumours¹. .....

http://www.nature.com/news/2009/090520/full/news.2009.493.html?s=news_rss

Artikulu interesgarri bat

2009-05-28T16:36:00.001+02:00

Argi Aldian

Mikel Iriondo. - EHUko Antropologia irakaslea

Hobbit

Artikulu interesgarria

2009-05-28T10:01:00.002+02:00

News and Views

Nature 459, 515-516 (28 May 2009) | doi:10.1038/459515a; Published online 27 May 2009

Developmental biology: Transgenic primate offspring

Gerald Schatten & Shoukhrat Mitalipov

Genetically engineered monkeys carrying a foreign gene that is passed on to their offspring provide a potentially valuable bridge between mouse models of disease and treatment for human disorders.

The development of transgenic mice — in which foreign DNA is inserted into the mouse genome — meant that the functions of human genes could be studied rigorously in living animals rather than in cell culture. Developments in transgene technology, complemented by advances in reproductive cloning, have followed in other mammals, including rats, rabbits, pigs, cows, and even cats and dogs. Sasaki et al.¹ (page 523 of this issue) now report a breakthrough in primate research — the generation of transgenic monkeys that pass the foreign gene on to their offspring and so could be used to establish specialized primate colonies for the study of human disease.

Mouse models of disease have been used in research into disorders ranging from anaemia and asthma to autism and schizophrenia. But not every human disease can be modelled faithfully in rodents. Mice engineered to express the cystic fibrosis gene, for example, do not develop the lung problems that typify this disorder (a pig model of cystic fibrosis² proved more useful). Disorders of higher brain function, such as Alzheimer's disease, are especially challenging to reproduce in rodents, and here, as with many other diseases, it is our closest animal relatives — the non-human primates — that offer potentially invaluable biological models.

In the United States, research with non-human primates can be conducted with stringent local and federal oversight. Consequently, this decade has seen the generation of a transgenic rhesus monkey³ and the first primate model of a human disorder, Huntington's disease, also in rhesus monkeys⁴. In another study, the transfer of a transgenic rhesus embryo generated a transgene-expressing placenta⁵. But no study has shown transmission of foreign DNA to gametes — the sperm and egg — which is essential for the generation of transgenic offspring. These offspring could then be bred to create transgenic-primate strains.

Sasaki et al.¹ build on this work, and introduce several innovations. Instead of rhesus monkeys, the authors studied the common marmoset (Callithrix jacchus) — small creatures that reach sexual maturity in just over a year, and that often bear twins after a relatively short gestation period. They found that naturally produced embryos, flushed from the reproductive tracts of mated females, were better transgene carriers than embryos generated by in vitro fertilization (IVF). After injection of the transgene, which encoded a green fluorescent protein (GFP) as a reporter of gene expression, nearly 100% of the natural embryos expressed the gene compared with about 70% of the IVF embryos — four of the five transgenic marmosets developed from these natural embryos.

To improve the efficiency of transgene delivery, the authors shrank the egg within its outer coating by placing it in a sugar solution, freeing up space for the injection of more transgene-containing particles. After transferring 80 embryos to 50 surrogate females, seven pregnancies were established, resulting in five offspring. The GFP transgene was incorporated into several sites in the offspring's genome and was expressed in various tissues, as confirmed by the green glow of the fluorescent protein. Furthermore, Sasaki et al. followed these animals until sexual maturity and found that the transgene was in their gametes, affording the tantalizing prospect of obtaining transgenic offspring through germline transmission. This hope came to fruition when the first infant conceived by the GFP-transgenic founder member also expressed GFP in its skin.

The birth of this transgenic marmoset baby is undoubtedly a milestone. The cumbersome and often frustrating process of making a transgenic animal from scratch need now only occur with founder animals. Subsequent generations can be produced by natural propagation, with the eventual establishment of transgene-specific monkey colonies — a potentially invaluable resource for studying incurable human disorders, and one that may also contribute to preserving endangered primate species. The study of transgenic primates may also help to answer fundamental questions about stem-cell biology. Primate stem cells have recently been generated from adult cells by nuclear cloning⁶, and a comparison of these cells with patient-specific induced pluripotent stem cells — also derived from adult cells — will be enlightening.

Transgenic marmosets are potentially useful models for research into infectious diseases, immunology and neurological disorders, for example. Marmosets engineered to express single-gene defects, such as the mutated gene that causes muscular dystrophy, might accelerate the translation of discoveries from mouse research⁷ to patients who have few treatment options. However, marmosets do have limitations as research models. They are New World primates, and are less closely related to humans than are Old World primates such as rhesus macaques and baboons. Because of biological differences, diseases such as HIV/AIDS, macular degeneration and tuberculosis can be studied only in Old World primates.

Also, despite the commendable success rates achieved by Sasaki et al.¹, their results pale in comparison with those achieved with mice. As in other primate studies, the authors use a virus vector to carry the transgene into the genome of the embryo after injection. Consequently, the transgene inserts into random sites in the target DNA. This is much less satisfactory than in transgenic mice, which are now routinely generated using embryonic stem cells. Here, the transgene is directly targeted to integrate into, or mutate, a specific site in the embryonic stem-cell genome by exploiting a natural genome repair process known as homologous recombination⁸. Random transgene integration probably resulted in some of the marmoset miscarriages; and as it could theoretically activate silent cancer-causing genes, or endogenous viral sequences that are part of the host genome, monitoring transgene inheritance in subsequent generations will be necessary.

As with all animal experimentation, genetic modification in primates raises concerns about animal welfare. We suggest that various considerations should be taken into account before colonies of primate disease models are established (Box 1). There are also bioethical concerns, which raise themselves anew with this work. Foremost among them is the prospect of unwarranted and unwise application of transgenic technologies to human gametes and embryos for reproductive purposes. Transgenic technologies are still primitive and inefficient, with unknown risks for animals, let alone people. Hence the very real need for the existing guidelines framed by professional societies and regulatory authorities (for example, those issued by the UK Human Fertilisation and Embryology Authority⁹), which prevent germline genetic modifications in humans. Perhaps even the use of techniques for generating embryonic stem cells from human embryos¹⁰ that have been genetically altered to prevent implantation, and that are therefore devoid of reproductive potential, needs to be weighed carefully so as to avoid going down any kind of slippery slope involving human transgenesis.

With recent breakthroughs in stem-cell research and these latest advances in primate developmental biology, increased attention will naturally be focused on the practices of human assisted reproductive technologies — hence the need to consider calls^11,¹² to establish realistic policies for governing work with human embryos. Although the future for using transgenic primates for medical and translational research looks bright, scientists need to engage with the public in informed bioethical debate about genetic modification and innovation in reproductive biology.

DNA egitura

2009-05-27T14:23:00.000+02:00

Sekuentziazio metodologia berriak

2009-05-27T09:15:00.001+02:00

Genome sequencer 454 FLX

Pirosekuentziazioa

2009-05-26T16:50:00.002+02:00

Pirosekuentziazioaren animazio oso inetersgarri bat

Artikulu interesgarri bat

2009-05-22T11:48:00.002+02:00

Why people with Down's syndrome get fewer cancers
Extra gene cuts growth of blood vessels that feed tumours.

Nature aldizkariko artikulu osoa

Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1

Kontseilu genetikoa.

2009-05-14T09:55:00.000+02:00

Farmakogenomika eta bularreko minbizia

2009-05-13T16:39:00.001+02:00

Pharmacogenomics and Breast Cancer

Dr. Hannah Linden, associate professor of medicine at the University of Washington, examines genomic heterogeneity, an emerging and important factor in determining tamoxifen benefit in breast cancer,........

Farmakogenomika eta minbizia

2009-05-13T16:11:00.004+02:00

Bideo honetan 14:30 minutuan farmakogenomika ingurua hitzegiten hasten da.

University of California TV

Farmakogenetika eta farmakogenomikare zenbait animazio

2009-05-13T16:03:00.002+02:00

Pharmacogenetics refers to the study of genetic influences on an individual’s response to drugs. In pharmacogenetics, the analysis of a specific gene, or group of genes, may be used to predict responses to a specific drug or class of drugs.

Pharmacogenomics refers collectively to all the genes that influence drug responses, and how genome-wide analysis may be used to identify such genes in the search for novel drug targets and/or key determinants of drug reactions

http://www.phgfoundation.org/tutorials/pharmacogenomics/public/rlo/intro.swf
http://www.phgfoundation.org/tutorials/pharmacogenomics/public/rlo/2.swf
http://www.phgfoundation.org/tutorials/pharmacogenomics/public/rlo/3.swf
http://www.phgfoundation.org/tutorials/pharmacogenomics/public/rlo/4.swf
http://www.phgfoundation.org/tutorials/pharmacogenomics/public/rlo/5.swf
http://www.phgfoundation.org/tutorials/pharmacogenomics/public/rlo/6.swf

Genetika Medikuntza Fakultatean

J.R. Bilbao genetika irakasleak artikulu honetan parte hartzen du.

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Aboriginal Genome Shows Two-Wave Settlement of Asia

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

Artikulu interesgarria

Transcriptomic analysis of autistic brain reveals convergent molecular pathology

Artikulu interesgarria

Royalactin induces queen differentiation in honeybees

Gene therapy finds its niche

Gene therapy finds its niche

Bifiduak jan behar?

Ebook gehiago

Cell Cycle and Cell Division Cell Cycle and Cell Division (ebook)

Essentials of Genetics (ebook)

Essentials of Genetics ebook-a aurkituko duzu

Oso informazio interesgarria "Nature ebooks"

Fisikako nobel saria: Izugarria!!!!!

Historia de un descubrimiento

The Nobel Prize in Physiology or Medicine 2010

Ingurunearen eragina pertsona heterozigotoetan

Revista Clínica Española

Fiebre y dolor abdominal tras el ascenso al Teide

Bibliografía

Poster bat nola egin

Colin Purrington, Department of Biology, Swarthmore College, Pennsylvania

Aldizkari interesgarri bat

Gene therapy: Targeting β-thalassaemia

Open Access Journal interesgarria "Orphanet Journal of Rare Diseases"

Ikasturte berria martxan

Bideo interesgarria

Artikulu interesgarria

Ancient DNA set to rewrite human history

Artikulu interesgarria

Genetics: An eye for colour

Artikulu interesgarria

High-density SNP genotyping detects homogeneity of Spanish and French Basques, and confirms their genomic distinctiveness from other European populations.

Abstract

Artikulu interesgarria

News and Views

Cancer: Genomics of metastasis

Abstract

Artikulu interesgarria

Big science: The cancer genome challenge

Artikulu interesgarria

Opinion

Let parents decide

Abstract

Tekniken inguruko animazioak

Genetikaren inguruko hainbat animazio

Sanger sekuentziazio metodoa

DNAren elektroforesia

Genetics: Random expression goes binary

News and Views

Abstract

Africa yields two full human genomes

Evolutionary biology: Face of the past reconstructed

Expansion of the eukaryotic proteome by alternative splicing

Towards building a chromosome segregation machine

Egiturazko akatsak

Inbertsioak eta meiosia

Proteinen elektroforesia

DNAren elektroforesia

Translokazioak eta meiosia

Meiosia

PCR

Diet and the evolution of human amylase gene copy number variation.

Y kromosoma aldakorra

Hardy-Weinberg legearen azalpen polita

Clinical pharmacology and pharmacogenetics in a genomics era: the DMET platform

Zutik

News and Views

Virology: Bornavirus enters the genome

Abstract

Artikulu interesgarri bat

Article

Complex landscapes of somatic rearrangement in human breast cancer genomes

Abstract

VIRUS OF THE YEAR 2009

VIRUS OF THE YEAR:

For years, scientists have been warning about the potentialfor an influenza pandemic on the order of the 1918 Spanish flu.But the pandemic that erupted last spring looks nothing likethe one health officials have been preparing to combat.

Evgeny I. Rogaev , Anastasia P. Grigorenko , Gulnaz Faskhutdinova , Ellen L. W. Kittler ³, Yuri K. Moliaka