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- Schroeder, Kari B., et al.
(författare)
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Haplotypic background of a private allele at high frequency in the Americas
- 2009
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 26:5, s. 995-1016
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Forskningsöversikt (refereegranskat)abstract
- Recently, the observation of a high-frequency private allele,the 9-repeat allele at microsatellite D9S1120, in all sampledNative American and Western Beringian populations has been interpretedas evidence that all modern Native Americans descend primarilyfrom a single founding population. However, this inference assumedthat all copies of the 9-repeat allele were identical by descentand that the geographic distribution of this allele had notbeen influenced by natural selection. To investigate whetherthese assumptions are satisfied, we genotyped 34 single nucleotidepolymorphisms across 500 kilobases (kb) around D9S1120 in 21Native American and Western Beringian populations and 54 otherworldwide populations. All chromosomes with the 9-repeat alleleshare the same haplotypic background in the vicinity of D9S1120,suggesting that all sampled copies of the 9-repeat allele areidentical by descent. Ninety-one percent of these chromosomesshare the same 76.26 kb haplotype, which we call the "AmericanModal Haplotype" (AMH). Three observations lead us to concludethat the high frequency and widespread distribution of the 9-repeatallele are unlikely to be the result of positive selection:1) aside from its association with the 9-repeat allele, theAMH does not have a high frequency in the Americas, 2) the AMHis not unusually long for its frequency compared with otherhaplotypes in the Americas, and 3) in Latin American mestizopopulations, the proportion of Native American ancestry at D9S1120is not unusual compared with that observed at other genomewidemicrosatellites. Using a new method for estimating the timeto the most recent common ancestor (MRCA) of all sampled copiesof an allele on the basis of an estimate of the length of thegenealogy descended from the MRCA, we calculate the mean timeto the MRCA of the 9-repeat allele to be between 7,325 and 39,900years, depending on the demographic model used. The resultssupport the hypothesis that all modern Native Americans andWestern Beringians trace a large portion of their ancestry toa single founding population that may have been isolated fromother Asian populations prior to expanding into the Americas.
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2. |
- Wood, Laura D, et al.
(författare)
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The genomic landscapes of human breast and colorectal cancers.
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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