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Linkage-disequilibrium approach for detecting genetic inter actions between extracellular and membrane molecules

用于检测细胞外分子和膜分子之间遗传相互作用的连锁不平衡方法

基本信息

批准号：
17570087
负责人：
TAKANO Toshiyuki
金额：
$ 2.37万
依托单位：
National Institute of Genetics
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17570087/
关键词：
Linkage disequilibrium Gene interaction Drosophila Natural selection Chemoreceptor

项目摘要

Many quantitative characters including complex genetic diseases are likely subject to truncation selection or other forms of multi-locus selection; however, direct measure of selection in natural populations remains difficult Multi-locus selection with epistasis can generate linkage disequilibrium from which we can infer the pattern and degree of selection and then functional connections of genes. Based on this idea, we studied polymorphisms in natural populations of D. melanogaster and obtained the following findings: 1) We found a large number of inter-locus nonrandom associations between polymorphisms in Drosophila chemoreceptor genes and a significant excess of haplotypes composed of one frequent and one less common allele in replacement but not silent polymorphisms. These results implied that multi-locus selection plays a significant role in shaping within-species variation, particularly to reduce frequencies of replacement polymorphisms that are slightly deleterious in combination with other polymorphisms. 2) We developed a new test to detect viability selection over a single generation. In this test, one specific type of chromosomes is chosen as a reference, while all other chromosomes are designated as focal. The test compares measures of variation between two groups of focal chromosomes: those found in reference/focal heterozygous individuals, and those found in focal/focal homozygotes. Currently acting selection can cause differences in some measures of variation. We applied this test to typing data for In (2L)t inversion polymorphism and X-linked chemoreceptor genes in Drosophila melanogaster populations and found evidence for selection. This new test and population genetics measures for linkage disequilibrium shed light on how often strong selection is operating in extant populations and serve to identify functional connections of genes.

包括复杂遗传疾病在内的许多数量性状可能受到截断选择或其他形式的多位点选择的影响；然而，直接测量自然种群中的选择仍然很困难，具有上位性的多位点选择可以产生连锁不平衡，从中我们可以推断选择的模式和程度，进而推断基因的功能联系。基于这一思想，我们对果蝇自然群体的多态性进行了研究，得到了以下结果：1)我们发现果蝇化学受体基因多态性在位点间存在大量非随机关联，替换多态性中存在大量由一个常见等位基因和一个不常见等位基因组成的单倍型，而沉默多态性中没有。这些结果表明，多位点选择在形成种内变异中起着重要作用，特别是在减少与其他多态性组合在一起略有有害的替代多态性的频率方面。我们开发了一种新的测试来检测单代的生存力选择。在这个测试中，选择一种特定类型的染色体作为参考，而所有其他染色体被指定为焦点。该测试比较了两组焦点染色体之间的差异：在参考/焦点杂合个体中发现的染色体，以及在焦点/焦点纯合子中发现的染色体。目前的行为选择可以在某些变异措施上造成差异。我们将该测试应用于黑腹果蝇种群的In (2L)t反转多态性和x连锁化学受体基因的分型数据，并找到了选择的证据。这个新的测试和种群遗传学测量连锁不平衡揭示了强选择在现存种群中运作的频率，并有助于识别基因的功能连接。