Extensive copy-number variation of the human olfactory receptor gene family.
Extensive copy-number variation of the human olfactory receptor gene family.
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DOI：
10.1016/j.ajhg.2008.07.005
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发表时间：
2008-08
影响因子：
9.8
通讯作者：
Janet M. Young;Raelynn M Endicott;Sean S. Parghi;M. Walker;J. Kidd;B. Trask
中科院分区：
文献类型：
--
作者：
Janet M. Young;Raelynn M Endicott;Sean S. Parghi;M. Walker;J. Kidd;B. Trask
据报道，多达四分之一的人类基因组在个体之间的拷贝数不同，包括包含大约一半嗅觉受体（OR）基因家族成员的区域。我们对OR基因的拷贝数变异进行了详细的研究，以阐明作用于该基因家族的选择性和机械性力量，以及拷贝数变异对人类OR基因库的真正影响。我们认为拷贝数变异（cnv）和其他大基因组区域的特性违反了通常用于评估基因富集的统计方法的假设。使用更合适的方法，我们提供了证据，证明cnv中的OR富集不是由于正选择，而是由于在片段复制区域的OR优势，这些区域通常是拷贝数可变的，并且因为在含有OR的区域中，针对cnv的纯化选择低于含有必需基因的区域。我们还结合多重连接依赖探针扩增（MLPA）和PCR来测定37个候选CNV or在50个人类个体中的拷贝数。我们确认了18个or的拷贝数变化，但发现其他16个or在人类多样性面板中没有变化，强调了报告的间隔通常夸大了真实CNVs的警告。我们所描述的拷贝数变异很可能是人类个体嗅觉能力显著差异的基础。最后，我们表明基于同源性和不依赖同源性的过程都在重塑OR家族中发挥了最近的作用。
As much as a quarter of the human genome has been reported to vary in copy number between individuals, including regions containing about half of the members of the olfactory receptor (OR) gene family. We have undertaken a detailed study of copy-number variation of ORs to elucidate the selective and mechanistic forces acting on this gene family and the true impact of copy-number variation on human OR repertoires. We argue that the properties of copy-number variants (CNVs) and other sets of large genomic regions violate the assumptions of statistical methods that are commonly used in the assessment of gene enrichment. Using more appropriate methods, we provide evidence that OR enrichment in CNVs is not due to positive selection but is because of OR preponderance in segmentally duplicated regions, which are known to be frequently copy-number variable, and because purifying selection against CNVs is lower in OR-containing regions than in regions containing essential genes. We also combine multiplex ligation-dependent probe amplification (MLPA) and PCR to assay the copy numbers of 37 candidate CNV ORs in a panel of ∼50 human individuals. We confirm copy-number variation of 18 ORs but find no variation in this human-diversity panel for 16 other ORs, highlighting the caveat that reported intervals often overrepresent true CNVs. The copy-number variation we describe is likely to underpin significant variation in olfactory abilities among human individuals. Finally, we show that both homology-based and homology-independent processes have played a recent role in remodeling the OR family.