USING DISEQUILIBRIUM MAPPING TO DISSECT COMPLEX TRAITS

使用不平衡映射来剖析复杂特征

• 批准号: 6627285
• 负责人: ANTHONY Douglas LONG
• 金额: $ 13.91万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627285
• 关键词: DNA; Drosophilidae; alleles; animal population genetics; computer data analysis; developmental genetics; gene expression; gene frequency; gene mutation; genetic polymorphism; linkage disequilibriums; linkage mapping; mathematical model; molecular cloning; nucleic acid sequence; oligonucleotides; phenotype; polymerase chain reaction; regulatory gene

Linkage disequilibrium mapping of DNA polymorphisms that contribute to variation in abdominal and steronpleural bristle number in large samples of wild caught Drosophila will be carried out in order to test a number of hypotheses: i) Do DNA polymorphisms at candidate genes contribute to standing variation in continuous characters?. ii) What are the frequencies and effects (including epistasis) of these polymorphisms, iii) What is the molecular nature (coding versus regulatory) of standing variation in quantitative traits?, iv) Are factors identified by association mapping consistent with those identified by QTL mapping, v) Is association mapping capable of being used effectively in humans to identify polymorphisms which contribute to complex disease phenotypes? Assessing the applicability of disequilibrium mapping to natural populations is crucial if we wish such studies to serve as a model for identifying human disease causing polymorphisms. In order to detect associations between DNA polymorphisms and genetic factors contributing a small fraction to standing variation in a quantitative character a large number of individuals must be typed for a large number of polymorphic DNA markers through a candidate gene region. This project focuses on three candidate genes, Delta, Notch, and Enhancer if Split, which are of central importance in the development of the peripheral nervous system (bristles are sensilla), and are particularly well characterized at the molecular level. Typing will be accomplished by first sequencing twenty alleles at each of the candidate genes to identify genes to identify all common polymorphisms that could potentially affect bristle number. Then, allele specific oligonucleotides are designed and hybridized to high density membranes on which long PCR products from approximately 4000 wild caught individuals are spotted. Hybridization patterns over sequential oligonucleotide probings allows each individual to be genotyped for a large number of polymorphic sites. Data will be examined for associations between polymorphic DNA sites and variation in bristle number, and regions containing sites with significant associations will be further typed to saturation to identify candidate causative polymorphisms. The set of candidate causative polymorphism will allow the above hypotheses to be directly addressed.

DNA多态性的连锁不平衡作图有助于 大样本腹侧鬃数变异 将进行野生捕获的果蝇，以测试一些 假设：i）候选基因的DNA多态性是否有助于 连续字符的固定变异？（二）频率是什么 以及这些多态性的影响（包括上位性），iii） 持续变异的分子本质（编码与调控） 数量性状？iv）是否通过关联映射确定因素 与通过QTL作图鉴定的那些一致，v）是关联作图 能够有效地用于人类以鉴定多态性 导致复杂的疾病表型评估 不平衡作图对自然群体的适用性是至关重要的 如果我们希望这样的研究能作为识别人类疾病的模型， 导致多态性。 为了检测DNA多态性与遗传易感性之间的关系， 因素贡献一小部分的常设变化在一个 一个数量性状，必须输入大量的个体， 通过候选基因区域的大量多态性DNA标记。 该项目主要关注三个候选基因，Delta，Notch和Enhancer 如果分裂，这是至关重要的发展， 周围神经系统（刚毛是感受器），特别是 在分子水平上得到了很好的表征。打字将通过以下方式完成： 首先对每个候选基因上的20个等位基因进行测序， 基因，以确定所有可能影响 刚毛数然后，设计等位基因特异性寡核苷酸， 与高密度膜杂交，在高密度膜上， 大约有4000只野生捕获的个体被发现。杂交 序列寡核苷酸探针的模式， 对大量多态位点进行基因分型。数据将 研究多态性DNA位点和变异之间的关联， 刚毛数量，以及包含具有显著关联的位点的区域 将被进一步键入到饱和度，以识别候选原因 多态性候选原因多态性的集合将允许 以上假设将被直接处理。

项目成果

Fine scale structural variants distinguish the genomes of Drosophila melanogaster and D. pseudoobscura.

• DOI: 10.1186/gb-2006-7-7-r67
• 发表时间: 2006
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Macdonald, Stuart J.;Long, Anthony D.
• 通讯作者: Long, Anthony D.

Changes in gene expression following high-temperature adaptation in experimentally evolved populations of E. coli.

实验进化的大肠杆菌群体高温适应后基因表达的变化。

• DOI: 10.1086/430035
• 发表时间: 2005
• 期刊: Physiological and biochemical zoology : PBZ.
• 作者: Riehle,MichelleM;Bennett,AlbertF;Long,AnthonyD
• 通讯作者: Long,AnthonyD

How repeatable are associations between polymorphisms in achaete-scute and bristle number variation in Drosophila?

• DOI: 10.1534/genetics.106.067108
• 发表时间: 2007-04-01
• 期刊: GENETICS
• 影响因子: 3.3
• 作者: Gruber, Jonathan D.;Genissel, Anne;Long, Anthony D.
• 通讯作者: Long, Anthony D.

Genetic architecture of thermal adaptation in Escherichia coli.

大肠杆菌热适应的遗传结构。

• DOI: 10.1073/pnas.98.2.525
• 发表时间: 2001
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Riehle,MM;Bennett,AF;Long,AD
• 通讯作者: Long,AD

Prospects for identifying functional variation across the genome.

识别整个基因组功能变异的前景。

• DOI: 10.1073/pnas.0501990102
• 发表时间: 2005
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Macdonald,StuartJ;Long,AnthonyD
• 通讯作者: Long,AnthonyD