Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations.
Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations.
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DOI：
10.2217/pgs.11.88
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发表时间：
2011-11
期刊：
影响因子：
2.1
通讯作者：
Tishkoff SA
中科院分区：
文献类型：
--
作者：
Mortensen HM;Froment A;Lema G;Bodo JM;Ibrahim M;Nyambo TB;Omar SA;Tishkoff SA
芳胺n -乙酰转移酶基因的功能变异性与人类的药物反应有关，并且可能在过去由于人类进化过程中饮食选择压力和毒素暴露而具有适应性。我们对全球人群（包括许多以前未被充分代表的非洲人群）中NAT1和NAT2基因以及NATP1伪基因的核苷酸变异进行了表征，以确定潜在的功能变异，并了解自然选择在全球不同人群中塑造这些基因座变异所起的作用。我们对197名非洲人和132名非非洲人的每个NAT1和NAT2基因区域以及伪基因NATP1进行了大约2800 bp的重新测序。我们在NAT1的3 ' -UTR中观察到平衡选择维持变异的特征，这表明这些变异可能发挥了目前未定义的功能作用。此外，我们观察到NAT2位点的高水平非同义功能变异在不同种族的人群中有所不同。
Functional variability at the arylamine N-acetyltransferase genes is associated with drug response in humans and may have been adaptive in the past owing to selection pressure from diet and exposure to toxins during human evolution. We have characterized nucleotide variation at the NAT1 and NAT2 genes, and at the NATP1 pseudogene in global human populations, including many previously under-represented African populations, in order to identify potential functional variants and to understand the role that natural selection has played in shaping variation at these loci in globally diverse populations. We have resequenced approximately 2800 bp for each of the NAT1 and NAT2 gene regions, as well as the pseudogene NATP1, in 197 African and 132 non-African individuals. We observe a signature of balancing selection maintaining variation in the 3’-UTR of NAT1, suggesting that these variants may play a functional role that is currently undefined. In addition, we observed high levels of nonsynonymous functional variation at the NAT2 locus that differs amongst ethnically diverse populations.