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Yali Xue,
Xuelong Zhang,
Ni Huang,
Allan Daly,
Christopher J Gillson,
Daniel G Macarthur, Bryndis Yngvadottir,
Alexandra C Nica,
Cara Woodwark,
Yuan Chen,
Donald F Conrad,
Qasim Ayub,
S Qasim Mehdi,
Pu Li,
Chris Tyler-Smith
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ABSTRACT: We have evaluated the extent to which SNPs identified by genomewide surveys as showing unusually high levels of population differentiation in humans have experienced recent positive selection, starting from a set of 32 nonsynonymous SNPs in 27 genes highlighted by the HapMap1 project. These SNPs were genotyped again in the HapMap samples and in the Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) panel of 52 populations representing worldwide diversity; extended haplotype homozygosity was investigated around all of them, and full resequence data were examined for 9 genes (5 from public sources and 4 from new data sets). For 7 of the genes, genotyping errors were responsible for an artifactual signal of high population differentiation and for 2, the population differentiation did not exceed our significance threshold. For the 18 genes with confirmed high population differentiation, 3 showed evidence of positive selection as measured by unusually extended haplotypes within a population, and 7 more did in between-population analyses. The 9 genes with resequence data included 7 with high population differentiation, and 5 showed evidence of positive selection on the haplotype carrying the nonsynonymous SNP from skewed allele frequency spectra; in addition, 2 showed evidence of positive selection on unrelated haplotypes. Thus, in humans, high population differentiation is (apart from technical artifacts) an effective way of enriching for recently selected genes, but is not an infallible pointer to recent positive selection supported by other lines of evidence.
Genetics 10/2009; 183(3):1065-77. · 4.01 Impact Factor
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ABSTRACT: The publication of the highest-quality and best-annotated personal genome yet tells us much about sequencing technology, something about genetic ancestry, but still little of medical relevance.
Genome biology 10/2009; 10(9):237. · 6.63 Impact Factor
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ABSTRACT: Nonsense SNPs introduce premature termination codons into genes and can result in the absence of a gene product or in a truncated and potentially harmful protein, so they are often considered disadvantageous and are associated with disease susceptibility. As such, we might expect the disrupted allele to be rare and, in healthy people, observed only in a heterozygous state. However, some, like those in the CASP12 and ACTN3 genes, are known to be present at high frequencies and to occur often in a homozygous state and seem to have been advantageous in recent human evolution. To evaluate the selective forces acting on nonsense SNPs as a class, we have carried out a large-scale experimental survey of nonsense SNPs in the human genome by genotyping 805 of them (plus control synonymous SNPs) in 1,151 individuals from 56 worldwide populations. We identified 169 genes containing nonsense SNPs that were variable in our samples, of which 99 were found with both copies inactivated in at least one individual. We found that the sampled humans differ on average by 24 genes (out of about 20,000) because of these nonsense SNPs alone. As might be expected, nonsense SNPs as a class were found to be slightly disadvantageous over evolutionary timescales, but a few nevertheless showed signs of being possibly advantageous, as indicated by unusually high levels of population differentiation, long haplotypes, and/or high frequencies of derived alleles. This study underlines the extent of variation in gene content within humans and emphasizes the importance of understanding this type of variation.
The American Journal of Human Genetics 03/2009; 84(2):224-34. · 10.60 Impact Factor
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04/2008; , ISBN: 9780470015902
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Bryndis Yngvadottir
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ABSTRACT: An EMBO workshop entitled 'Human Evolution and Disease' was held recently (6-9 December 2006, Hyderabad, India) where 141 scientists from many disciplines came together to discuss recent studies of human variation, origins and dispersal, natural selection and disease susceptibility. The meeting tackled the subject of human evolution and disease from the different perspectives of archaeology, linguistics, genetics and genomics based on both new and publicly available data sets. In this report, we highlight the latest fashion crazes in the discipline, in particular, the use of large public data sets and new methods to analyse modern human variation and the links between human evolution and disease susceptibility.
European Journal of HumanGenetics 06/2007; 15(5):603-6. · 4.40 Impact Factor
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ABSTRACT: Arab forces conquered the Indus Delta region in 711 AD: and, although a Muslim state was established there, their influence was barely felt in the rest of South Asia at that time. By the end of the tenth century, Central Asian Muslims moved into India from the northwest and expanded throughout the subcontinent. Muslim communities are now the largest minority religion in India, comprising more than 138 million people in a predominantly Hindu population of over one billion. It is unclear whether the Muslim expansion in India was a purely cultural phenomenon or had a genetic impact on the local population. To address this question from a male perspective, we typed eight microsatellite loci and 16 binary markers from the Y chromosome in 246 Muslims from Andhra Pradesh, and compared them to published data on 4,204 males from East Asia, Central Asia, other parts of India, Sri Lanka, Pakistan, Iran, the Middle East, Turkey, Egypt and Morocco. We find that the Muslim populations in general are genetically closer to their non-Muslim geographical neighbors than to other Muslims in India, and that there is a highly significant correlation between genetics and geography (but not religion). Our findings indicate that, despite the documented practice of marriage between Muslim men and Hindu women, Islamization in India did not involve large-scale replacement of Hindu Y chromosomes. The Muslim expansion in India was predominantly a cultural change and was not accompanied by significant gene flow, as seen in other places, such as China and Central Asia.
Human Genetics 12/2006; 120(4):543-51. · 5.07 Impact Factor
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Yali Xue,
Allan Daly, Bryndis Yngvadottir,
Mengning Liu,
Graham Coop,
Yuseob Kim,
Pardis Sabeti,
Yuan Chen,
Jim Stalker,
Elizabeth Huckle,
John Burton,
Steven Leonard,
Jane Rogers,
Chris Tyler-Smith
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ABSTRACT: The human caspase-12 gene is polymorphic for the presence or absence of a stop codon, which results in the occurrence of both active (ancestral) and inactive (derived) forms of the gene in the population. It has been shown elsewhere that carriers of the inactive gene are more resistant to severe sepsis. We have now investigated whether the inactive form has spread because of neutral drift or positive selection. We determined its distribution in a worldwide sample of 52 populations and resequenced the gene in 77 individuals from the HapMap Yoruba, Han Chinese, and European populations. There is strong evidence of positive selection from low diversity, skewed allele-frequency spectra, and the predominance of a single haplotype. We suggest that the inactive form of the gene arose in Africa approximately 100-500 thousand years ago (KYA) and was initially neutral or almost neutral but that positive selection beginning approximately 60-100 KYA drove it to near fixation. We further propose that its selective advantage was sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased.
The American Journal of Human Genetics 05/2006; 78(4):659-70. · 10.60 Impact Factor
