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定量特征可能会受到截短选择或其他形式的多层次选择；但是，自然种群中选择的直接度量仍然很难用上位数的多洛克斯选择，可以产生连锁不平衡，我们可以从中推断出选择模式和程度，然后是基因的功能连接。基于这个想法，我们研究了D. melanogaster的自然种群中的多态性，并获得了以下发现：1）我们发现，在果蝇化学感受器基因的多态性之间存在大量的非固定型非随机相关性，而在一个频繁的频繁和替换中的单plot型型却很大，但不是替换了一个频繁的非频率，但不是无人常见的专利型。这些结果表明，多级别的选择在塑造物种内部变化中起重要作用，尤其是为了降低替代多态性的频率，这些多态性与其他多态性相结合。 2）我们开发了一项新的测试，以检测单代的生存能力选择。在此测试中，选择一种特定类型的染色体作为参考，而所有其他染色体则被指定为焦点。该测试比较了两组焦染色体之间变异的测量：参考/局灶性杂合个体中发现的染色体，以及在局灶性/局灶性纯合子中发现的。当前的作用选择可能会导致某些变化措施的差异。我们将此测试应用于果蝇种群中（2L）T反转多态性和X连锁化学感受器基因的数据，并找到了选择的证据。这种新的测试和种群遗传学测量连锁不平衡的方法揭示了在现存的人群中进行强有力的选择的频率，并有助于识别基因的功能连接。