Prospects for identifying functional variation across the genome.
Prospects for identifying functional variation across the genome.
复制标题
识别整个基因组功能变异的前景。
DOI：
10.1073/pnas.0501990102
复制
发表时间：
2005
影响因子：
11.1
通讯作者：
Long,AnthonyD
中科院分区：
文献类型：
--
作者：
Macdonald,StuartJ;Long,AnthonyD
导致复杂性状变异的遗传因素可能存在于基因组的调控部分，而不是蛋白质编码部分。在非编码区域内，调控元件中的 SNP 比非调控区域中的 SNP 更有可能导致表型变异。因此，能够识别和注释非编码调控元件非常重要。不同物种之间的 DNA 保护成功地识别了非编码调控区域。然而，由于快速进化的调控区域通常不会在物种之间得到保护，因此使用纯粹基于保护的方法无法检测到这些区域。在这里，我们描述了可用于通过非中性进化的特征来识别假定的调控元件的其他方法。对黑腹果蝇种群内部和种群之间的多态性模式的检查，以及与其兄弟物种模拟果蝇的差异，在 24.2 kb 的非编码 DNA 中确定了几个未通过保护识别的非中性进化区域。由于不同的方法标记不同的区域，因此这些方法似乎是互补的。不同元素的变异模式与选择性扫描、平衡选择或群体分化的作用一致。连同 D 之间保留的区域。黑腹果蝇和伪暗果蝇，我们将 5.3 kb 的非编码 DNA 标记为潜在的调节性。所调查的 408 个常见非编码 SNP 中有 97 个位于假定的监管区域内。如果这些方法共同鉴定出大多数功能性非编码多态性，则在关联作图框架中仅对这些 SNP 进行基因分型将减少非编码区域基因分型工作量 4 倍。
The genetic factors contributing to complex trait variation may reside in regulatory, rather than protein-coding portions of the genome. Within noncoding regions, SNPs in regulatory elements are more likely to contribute to phenotypic variation than those in nonregulatory regions. Thus, it is important to be able to identify and annotate noncoding regulatory elements. DNA conservation among diverged species successfully identifies noncoding regulatory regions. However, because rapidly evolving regulatory regions will not generally be conserved across species, these will not detected by using purely conservation-based methods. Here we describe additional approaches that can be used to identify putative regulatory elements via signatures of nonneutral evolution. An examination of the pattern of polymorphism both within and between populations ofDrosophila melanogaster, as well as divergence with its sibling speciesDrosophila simulans, across 24.2 kb of noncoding DNA identifies several nonneutrally evolving regions not identified by conservation. Because different methods tag different regions, it appears that the methods are complementary. Patterns of variation at different elements are consistent with the action of selective sweeps, balancing selection, or population differentiation. Together with regions conserved betweenD. melanogasterandDrosophila pseudoobscura, we tag 5.3 kb of noncoding DNA as potentially regulatory. Ninety-seven of the 408 common noncoding SNPs surveyed are within putatively regulatory regions. If these methods collectively identify the majority of functional noncoding polymorphisms, genotyping only these SNPs in an association mapping framework would reduce genotyping effort for noncoding regions 4-fold.