Discovery and Characterization of Quantitative Trait Nucleotides

数量性状核苷酸的发现和表征

基本信息

批准号：
8507755
负责人：
Matthew Rockman
金额：
$ 28.87万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8507755
关键词：
Affect Agriculture Alleles Anecdotes Architecture Behavioral Biology C. elegans genome Caenorhabditis elegans Cataloging Catalogs Collection Complex Complex Genetic Trait Complex Mixtures Data Development Disease Dissection Environment Frequencies Gene Frequency Genes Genetic Genetic Epistasis Genetic Polymorphism Genetic Recombination Genetic Variation Genome Genomics Genotype Goals Health Heritability Human Inbreeding Individual Knowledge Learning Left Maps Measures Methods Modeling Molecular Mutation Nematoda Nucleotide Mapping Nucleotides Organism Phenotype Physiology Population Population Distributions Population Genetics Predisposition Quantitative Trait Loci Reading Recombinants Reporter Research Resolution Resources Shapes Sorting - Cell Movement Specificity Staging Tissues Transcript Transgenic Organisms Variant X Chromosome abstracting base design disorder risk genetic variant genome wide association study genome-wide human disease pleiotropism success therapy development tool trait

项目摘要

(4.4.6) PROJECT SUMMARY/ABSTRACT Heritable variation underlies variation in human health, and the molecular basis for that variation is largely uncharacterized. Recent results suggest that heritable variation in human disease risk may be shaped by a complex mixture of rare alleles, common alleles of small effect, and alleles of all frequencies whose effects depend on allelic states at other loci. Such complexity is expected for quantitative traits under stabilizing selection, such as human physiology, and the complex architecture of such traits is a major obstacle to their genetic dissection. Knowledge of the genetic variants underlying complex traits is central to methods for ameliorating or predicting disease risk and for developing therapies for treatment. Transcript abundance traits in the nematode C. elegans are a promising model for variation in complex traits under stabilizing selection. These traits are amenable to full genetic dissection using panel of near-isogenic inbred lines of that vary within a small interval of the X chromosome implicated in heritable variation in hundreds of transcript abundance traits. Creation and study of such a permanent mapping resource will permit identification of the causal variants underlying variation in transcript abundances at the resolution of individual sequence variants, generating a catalog of quantitative trait nucleotides. Such a catalog will reveal the types of mutations that contribute to variation in complex traits, their modes of action, their additive and interactive effect sizes, their frequencies in natural populations, and the distribution of their effects across tissues and developmental stages and environments. Quantitative trait nucleotides mapped to single-variant resolution have never been collected for any multicellular organism, and their features will inform efforts to discover the genetic basis of complex disease traits in humans.

（4.4.6）项目摘要/摘要可遗传的变异是人类健康的差异的基础，而这种变化的分子基础是在很大程度上没有特色。最近的结果表明，人类疾病风险的可遗传差异可能是由稀有等位基因的复杂混合物，小效应的常见等位基因和所有等位基因形成效果取决于其他基因座的等位基因状态的频率。期望如此复杂稳定选择的定量性状，例如人类生理和复杂的结构这种特征是其遗传解剖的主要障碍。遗传变异的知识潜在的复杂性状是改善或预测疾病风险的方法以及开发治疗疗法。线虫C.秀丽隐杆线虫中的成绩单丰度特征是在稳定选择下复杂性状变化的有希望的模型。这些特征是可以正常的使用该面板在较小的间隔内使用该近亲的近交近交系列面板进行全遗传解剖 X染色体涉及数百种转录特征的遗传变化。创建和研究这种永久映射资源将允许识别因果关系在单个序列分辨率下，转录物丰度变化的变异变异变体，生成定量性状核苷酸的目录。这样的目录会揭示导致复杂特征，其作用方式，其添加剂和的突变互动效应大小，自然种群中的频率及其效果的分布跨组织，发育阶段和环境。定量性状核苷酸映射到从未为任何多细胞生物及其特征收集单变量的分辨率将告知人们发现人类复杂疾病特征的遗传基础的努力。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cryptic genetic variation: evolution's hidden substrate.

DOI：
10.1038/nrg3688
发表时间：
2014-04
期刊：
Nature reviews. Genetics
影响因子：
0
作者：
Paaby AB;Rockman MV
通讯作者：
Rockman MV

Multigenic natural variation underlies Caenorhabditis elegans olfactory preference for the bacterial pathogen Serratia marcescens.

DOI：
10.1534/g3.113.008649
发表时间：
2014-02-19
期刊：
G3 (Bethesda, Md.)
影响因子：
0
作者：
Glater EE;Rockman MV;Bargmann CI
通讯作者：
Bargmann CI

The QTN program and the alleles that matter for evolution: all that's gold does not glitter.

DOI：
10.1111/j.1558-5646.2011.01486.x
发表时间：
2012-01
期刊：
Evolution; international journal of organic evolution
影响因子：
0
作者：
Rockman MV
通讯作者：
Rockman MV

Natural Variation in plep-1 Causes Male-Male Copulatory Behavior in C. elegans.

DOI：
10.1016/j.cub.2015.09.019
发表时间：
2015-10-19
期刊：
Current biology : CB
影响因子：
0
作者：
Noble LM;Chang AS;McNelis D;Kramer M;Yen M;Nicodemus JP;Riccardi DD;Ammerman P;Phillips M;Islam T;Rockman MV
通讯作者：
Rockman MV

Resistance to germline RNA interference in a Caenorhabditis elegans wild isolate exhibits complexity and nonadditivity.