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

许多数量性状，包括复杂的遗传疾病，可能会受到截断选择或其他形式的多位点选择，然而，在自然群体中的选择的直接措施仍然是困难的。多位点选择与上位性可以产生连锁不平衡，我们可以推断的模式和选择的程度，然后功能连接的基因。基于这一思想，我们研究了D.结果表明：1）果蝇化学感受器基因多态性位点间存在大量的非随机关联，并且在替代位点上存在由一个常见等位基因和一个不常见等位基因组成的显著过量的单倍型，但不存在沉默多态性。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，特别是减少与其他多态性结合时略微有害的替换多态性的频率。2)我们开发了一种新的测试来检测单代的生存力选择。在该测试中，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。该测试比较了两组局灶性染色体之间的变异测量：在参考/局灶性杂合子个体中发现的那些，以及在局灶性/局灶性纯合子中发现的那些。当前的行为选择可以导致某些变异度量的差异。我们应用此测试分型数据在（2L）t倒位多态性和X连锁的化学感受器基因在果蝇种群，并发现选择的证据。这种新的测试和群体遗传学措施连锁不平衡揭示了如何经常强选择是在现存的人口中运作，并有助于确定基因的功能连接。

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.