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The many GWA studies utilizing the DGRP have revealed substantial natural genetic variation for all reported traits, little evidence for variants with large effects but enrichment for variants with low P-values, and a tendency for lower frequency variants to have larger effects than more common variants. The variants detected in the GWA analyses rarely overlap those discovered using mutagenesis, and often are the first functional annotations of computationally predicted genes. Variants implicated in GWA analyses typically have sex-specific and genetic background-specific (epistatic) effects, as well as pleiotropic effects on other quantitative traits. Studies in the DGRP reveal substantial genetic control of environmental variation. Taking account of genetic architecture can greatly improve genomic prediction in the DGRP. These features of the genetic architecture of quantitative traits are likely to apply to other species, including humans. 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The variants detected in the GWA analyses rarely overlap those discovered using mutagenesis, and often are the first functional annotations of computationally predicted genes. Variants implicated in GWA analyses typically have sex-specific and genetic background-specific (epistatic) effects, as well as pleiotropic effects on other quantitative traits. Studies in the DGRP reveal substantial genetic control of environmental variation. Taking account of genetic architecture can greatly improve genomic prediction in the DGRP. These features of the genetic architecture of quantitative traits are likely to apply to other species, including humans. 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引用次数: 0
摘要
了解数量性状的遗传结构(因果分子变异、其影响和频率)对于精准农业和医学以及预测适应性进化非常重要,但在大多数物种中却具有挑战性。黑腹果蝇遗传参比群体(DGRP)由 205 个近交系组成,其全基因组序列来自美国北卡罗来纳州罗利市的一个野生种群。DGRP 和源自 DGRP 品系的近交种群中存在大量的数量遗传变异,缺乏种群结构,且连锁不平衡在局部迅速衰减,这为进行全基因组关联(GWA)图谱分析以确定影响数量性状的候选因果基因、多态性和途径提供了有利条件。利用 DGRP 进行的多项 GWA 研究表明,所有报告的性状都存在大量的天然遗传变异,几乎没有证据表明变异具有较大的影响,但 P 值较低的变异却很丰富,而且低频率变异的影响往往大于较常见的变异。GWA 分析中检测到的变异很少与诱变发现的变异重叠,而且往往是计算预测基因的首次功能注释。GWA 分析中涉及的变异通常具有性别特异性和遗传背景特异性(表观)效应,以及对其他数量性状的多向效应。DGRP 的研究揭示了环境变异的大量遗传控制。考虑遗传结构可大大改善 DGRP 的基因组预测。数量性状遗传结构的这些特点很可能适用于包括人类在内的其他物种。WIREs Dev Biol 2018, 7:e289. doi: 10.1002/wdev.289 This article is categorized under:无脊椎动物器官发生 > 苍蝇。
Charting the genotype-phenotype map: lessons from the Drosophila melanogaster Genetic Reference Panel.
Understanding the genetic architecture (causal molecular variants, their effects, and frequencies) of quantitative traits is important for precision agriculture and medicine and predicting adaptive evolution, but is challenging in most species. The Drosophila melanogaster Genetic Reference Panel (DGRP) is a collection of 205 inbred strains with whole genome sequences derived from a single wild population in Raleigh, NC, USA. The large amount of quantitative genetic variation, lack of population structure, and rapid local decay of linkage disequilibrium in the DGRP and outbred populations derived from DGRP lines present a favorable scenario for performing genome-wide association (GWA) mapping analyses to identify candidate causal genes, polymorphisms, and pathways affecting quantitative traits. The many GWA studies utilizing the DGRP have revealed substantial natural genetic variation for all reported traits, little evidence for variants with large effects but enrichment for variants with low P-values, and a tendency for lower frequency variants to have larger effects than more common variants. The variants detected in the GWA analyses rarely overlap those discovered using mutagenesis, and often are the first functional annotations of computationally predicted genes. Variants implicated in GWA analyses typically have sex-specific and genetic background-specific (epistatic) effects, as well as pleiotropic effects on other quantitative traits. Studies in the DGRP reveal substantial genetic control of environmental variation. Taking account of genetic architecture can greatly improve genomic prediction in the DGRP. These features of the genetic architecture of quantitative traits are likely to apply to other species, including humans. WIREs Dev Biol 2018, 7:e289. doi: 10.1002/wdev.289 This article is categorized under: Invertebrate Organogenesis > Flies.
期刊介绍:
Developmental biology is concerned with the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex, fully patterned adult organism. This problem is studied on many different biological levels, from the molecular to the organismal. Developed in association with the Society for Developmental Biology, WIREs Developmental Biology will provide a unique interdisciplinary forum dedicated to fostering excellence in research and education and communicating key advances in this important field. The collaborative and integrative ethos of the WIREs model will facilitate connections to related disciplines such as genetics, systems biology, bioengineering, and psychology.
The topical coverage of WIREs Developmental Biology includes: Establishment of Spatial and Temporal Patterns; Gene Expression and Transcriptional Hierarchies; Signaling Pathways; Early Embryonic Development; Invertebrate Organogenesis; Vertebrate Organogenesis; Nervous System Development; Birth Defects; Adult Stem Cells, Tissue Renewal and Regeneration; Cell Types and Issues Specific to Plants; Comparative Development and Evolution; and Technologies.