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Recent human evolution has shaped geographical differences in susceptibility to disease

  • Marigorta, Urko M.
  • Lao Grueso, Oscar, 1976-
  • Casals López, Ferran
  • Calafell i Majó, Francesc
  • Morcillo Suárez, Carlos, 1969-
  • Faria, Rui
  • Bosch Fusté, Elena
  • Serra, François
  • Bertranpetit, Jaume, 1952-
  • Dopazo, Hernán
  • Navarro i Cuartiellas, Arcadi, 1969-
Background: Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies./nResults: We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions: Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.
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The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild

  • Prado Martínez, Javier, 1987-
  • Hernando Herráez, Irene, 1985-
  • Lorente-Galdós, Belén, 1981-
  • Dabad, Marc
  • Ramírez, Oscar
  • Baeza Delgado, Carlos
  • Morcillo Suárez, Carlos, 1969-
  • Alkan, Can
  • Hormozdiari, Fereydoun
  • Raineri, Emanuele
  • Estellé, Jordi
  • Fernández Callejo, Marcos
  • Vallès, Mònica
  • Ritscher, Lars
  • Schöneberg, Torsten
  • Calle Mustienes, Elisa de la
  • Casillas, Sònia
  • Rubio Acero, Raquel
  • Melé Messeguer, Marta, 1982-
  • Engelken, Johannes
  • Cáceres Aguilar, Mario
  • Gómez Skarmeta, José Luis
  • Gut, Marta
  • Bertranpetit, Jaume, 1952-
  • Gut, Ivo Glynne
  • Abelló, Teresa
  • Eichler, Evan E.
  • Mingarro, Ismael
  • Lalueza Fox, Carles, 1965-
  • Navarro i Cuartiellas, Arcadi, 1969-
  • Marquès i Bonet, Tomàs, 1975-
BACKGROUND: The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas./n/nRESULTS: We successfully identified the causal genetic variant for Snowflake's albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake's parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla./n/nCONCLUSIONS: In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost., This work was supported by an ERC Starting Grant (StG_20091118) to TM-B
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Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD

  • Bosch Fusté, Elena
  • Laayouni, Hafid, 1968-
  • Morcillo Suárez, Carlos, 1969-
  • Casals López, Ferran
  • Moreno Estrada, Andrés
  • Ferrer Admetlla, Anna
  • Gardner, Michelle
  • Rosa, Araceli
  • Comas, David, 1969-
  • Graffelman, Jan
  • Calafell i Majó, Francesc
  • Bertranpetit, Jaume, 1952-
Background: It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8./nResults: Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. Conclusion: The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.
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Towards the automatic merging of language resources

  • Necşulescu, Silvia
  • Bel Rafecas, Núria
  • Padró, Muntsa
  • Marimon, Montserrat
  • Revilla, Eva
Language Resources are a critical component for Natural Language Processing applications. Throughout the years many resources were manually created for the same task, but with different granularity and coverage information. To create richer resources for a broad range of potential reuses, nformation from all resources has to be joined into one. The hight cost of comparing and merging different resources by hand has been a bottleneck for merging existing resources. With the objective of reducing human intervention, we present a new method for automating merging resources. We have addressed the merging of two verbs subcategorization frame (SCF) lexica for Spanish. The results achieved, a new lexicon with enriched information and conflicting information signalled, reinforce our idea that this approach can be applied for other task of NLP.
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Towards the Fully Automatic Merging of Lexical Resources: A Step Forward

  • Padró, Muntsa
  • Bel Rafecas, Núria
  • Necşulescu, Silvia
This article reports on the results of the research done towards the fully automatically merging of lexical resources. Our main goal is to show the generality of the proposed approach, which have been previously applied to merge Spanish Subcategorization Frames lexica. In this work we extend and apply the same technique to perform the merging of morphosyntactic lexica encoded in LMF. The experiments showed that the technique is general enough to obtain good results in these two different tasks which is an important step towards performing the merging of lexical resources fully automatically.
Proyecto:


A Method Towards the Fully Automatic Merging of Lexical Resources

  • Bel Rafecas, Núria
  • Padró, Muntsa
  • Necşulescu, Silvia
Lexical Resources are a critical component for Natural Language Processing applications. However, the high cost of comparing and merging different resources has been a bottleneck to obtain richer resources and a broader range of potential uses for a significant number of languages. With the objective of reducing cost by eliminating human intervention, we present a new method towards the automatic merging of resources. This method includes both, the automatic mapping of resources involved to a common format and merging them, once in this format. This paper presents how we have addressed the merging of two verb subcategorization frame lexica for Spanish, but our method will be extended to cover other types of Lexical Resources. The achieved results, that almost replicate human work, demonstrate the feasibility of the approach.
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