Suchergebnisse

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene under/nhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences./nAdditionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,/n20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39/nworldwide human populations from the HGDP-CEPH diversity panel./nResults: The genome sequences recently available from other primate and non-primate species showed that FOXI1/ndivergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant in/nEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsb/nstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recent/nepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on the/nputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies strongly/ncorrelated with the absolute geographical latitude of the populations sampled./nConclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate might/nbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediated/nwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation. ; This research was funded by grant BFU2005-00243 awarded by Dirección General de Investigación, Ministerio de Educación y Ciencia (Spain), by grant BFU2008-01046/BMC awarded by Subdirección General de Proyectos de Investigación, Ministerio de Ciencia e Innovación (Spain), and by the Direcció General de Recerca, Generalitat de Catalunya (2009SGR1101). AME was supported by a CONACYT fellowship from the Mexican government (grant 179339), MS by a PhD fellowship from the Programa de becas FPU del Ministerio de Educación y Ciencia, Spain (AP2005-3982) and JE by a Volkswagenstiftung scholarship (I/82 750). SNP genotyping services were provided by the Spanish "Centro Nacional de Genotipado" (http://www.cegen.org).

Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD) have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America). The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe) on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total) communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD. ; This study was supported by the European Project QLG2-CT-2001-00916 and by the Ministerio de Ciencia y Tecnologia of the Spanish Government (BNC2001-0772).

Haplogroup R1b-M269 comprises most Western European Y chromosomes; of its main branches, R1b-DF27 is by far the least known, and it appears to be highly prevalent only in Iberia. We have genotyped 1072 R1b-DF27 chromosomes for six additional SNPs and 17 Y-STRs in population samples from Spain, Portugal and France in order to further characterize this lineage and, in particular, to ascertain the time and place where it originated, as well as its subsequent dynamics. We found that R1b-DF27 is present in frequencies ~40% in Iberian populations and up to 70% in Basques, but it drops quickly to 6-20% in France. Overall, the age of R1b-DF27 is estimated at ~4,200 years ago, at the transition between the Neolithic and the Bronze Age, when the Y chromosome landscape of W Europe was thoroughly remodeled. In spite of its high frequency in Basques, Y-STR internal diversity of R1b-DF27 is lower there, and results in more recent age estimates; NE Iberia is the most likely place of origin of DF27. Subhaplogroup frequencies within R1b-DF27 are geographically structured, and show domains that are reminiscent of the pre-Roman Celtic/Iberian division, or of the medieval Christian kingdoms. ; Funding was provided by the Agencia Estatal de Investigación and Fondo Europeo de Desarollo Regional (FEDER) (grants CGL2013-44351-P, CGL2016-75389-P), by Agència de Gestió d'Ajuts Universitaris i de la Recerca (Generalitat de Catalunya) grant 2014 SGR 866, and by the Basque Government (IT-424-07). FT was supported by the ERC Advanced Grant Agreement No 295733, 'LanGeLin' project