Genetic variation of olfactory receptor gene family in a Japanese population
Genetic variation of olfactory receptor gene family in a Japanese population
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DOI：
10.1537/ase.211024
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发表时间：
2022-01-01
影响因子：
0.7
通讯作者：
Kawamura, Shoji
中科院分区：
文献类型：
--
作者：
Akhtar, Muhammad Shoaib;Ashino, Ryuichi;Kawamura, Shoji
嗅觉受体（OR）基因家族由数百个完整和破坏的基因组成。个体间OR基因的组成和拷贝数变异（CNV）可能导致嗅觉感知的变异。然而，很少有人知道在许多人群中的OR遗传变异。在这项研究中，我们使用靶向捕获富集和大规模平行短读测序方法来检查OR基因的遗传变异，以及作为参考的中性基因组区域，为69个匿名的无关日本个体。捕获探针设计用于人参考基因组hg 38中的398个完整OR基因和85个中性参考。探针也被设计为4个未注释的和99个“几乎完整的”（hg 38-伪）或基因在hg 38和53黑猩猩或基因在Pantro3.0基因组数据库中没有直系同源物在hg 38。检索到所有hg 38 OR基因和1个Pantro 3.0 OR基因。平均测序深度明显高于1000基因组计划。新发现了来自hg 38-完整和hg 38-假类别的共30个OR基因为分离假基因。一个hg 38-假OR基因在所有个体中是完整的。在63个OR基因中检测到CNV。Tajima对OR基因和中性参照的D分析与平衡选择一致，以保持完整OR基因中的等位基因差异。这些结果表明，具有多样性导向设计的探针的靶向捕获远比全基因组方法更有效地检索OR基因并实现高深度测序，从而揭示OR多基因家族的多态性。人类参考基因组hg 38中OR基因的组成并不一定代表许多人的组成，这意味着感知变异比以前认为的要高。目前的研究激发了在全球范围内采用类似方法的进一步调查。
The olfactory receptor (OR) gene family is comprised of hundreds of intact and disrupted genes in humans. The compositions and copy number variation (CNV) of disrupted and intact OR genes among individuals is expected to cause variation in olfactory perception. However, little is known about OR genetic variation in many human populations. In this study, we used targeted capture enrichment and massive parallel short-read sequencing methods to examine genetic variation of OR genes, as well as of neutral genome regions as references, for 69 anonymized unrelated Japanese individuals. The capture probes were designed for 398 intact OR genes in the human reference genome hg38, and 85 neutral references. Probes were also designed for four unannotated and 99 'nearly-intact' (hg38-pseudo) OR genes in hg38 and 53 chimpanzee OR genes in the Pantro3.0 genome database with no orthologs in hg38. All the hg38 OR genes and one Pantro 3.0 OR gene were retrieved. The mean sequencing depth was significantly higher than that of the 1000 Genomes Project. A total of 30 OR genes from hg38-intact and hg38-pseudo categories were newly found to be segregating pseudogenes. One hg38-pseudo OR gene was intact in all individuals. CNV was detected in 63 OR genes. Tajima's D analysis for OR genes and neutral references was consistent with balancing selection to maintain allelic differences in intact OR genes. These results demonstrate that the targeted capture by probes with diversity-oriented design is far more effective than a whole-genome approach to retrieve OR genes and achieve high-depth sequencing and thus to reveal polymorphisms for the OR multigene family. The composition of OR genes in the human reference genome hg38 does not necessarily represent those in many humans, implying higher perceptual variation than previously thought. The current study inspires further investigation with a similar approach at a global scale.