GENETIC EFFECTS OF GENOMIC IMPRINTING ON BODY SIZE

本研究的目的是应用一种新开发的研究设计， 寻找有助于遗传的数量性状基因座（QTL） 出生体重、体型和青少年生长的变化，以及 确定检测到的任何QTL是否受到以下因素的影响： 基因组印记 DNA样本将从600个单合子 (MZ)和双卵（DZ）双胞胎及其父母，并进行225分型 多态性标记以大约15 cM的间隔分布在整个基因组中。 基因组 使用亲本分型数据，DZ对将被分类 根据它们共享的等位基因分为四组， 下降（IBD）在每个标记位点，并与MZ对谁共享 两个等位基因IBD在标记和所有其他基因座以及。 定量 对所得数据的遗传分析将允许估计 表型的遗传变异以及可归因的命题 分别与任何紧密连锁的QTL和QTL的印记效应相关。 搜索将从10个选定的候选基因座开始，包括INS，IGF 1， IGF2、IGF1R、IGF2R、GH1、GH2、GHR、GHRF和SNRPN。 结果IBD 评分双胞胎样本将是一个非常宝贵的资源， 用于搜索影响任何遗传数量性状的QTL。 在这一人群中已经有了广泛的纵向数据， 多种人体测量、心血管和生化变量， 将接受这些分析。

The goal of this research is to apply a newly developed research design to search for quantitative trait loci (QTL's) that contribute to genetic variation in birth weight, body size and adolescent growth, and to determine whether any of the QTL's that are detected, are influenced by genomic imprinting. DNA samples will be obtained from 600 monozygotic (MZ) and dizygotic (DZ) twins and their parents and typed for 225 polymorphic markers spaced at approximately 15 cM intervals throughout the genome. Using the parental typing data, the DZ pairs will be classified into four groups according to the alleles they share that are identical by descent (IBD) at each marker locus and compared with MZ pairs who share two alleles IBD at the marker and at all other loci as well. Quantitative genetic analysis of the resulting data will permit estimation of the total genetic variation in the phenotype as well as the proposition attributable to any closely linked QTL and imprinting effects of the QTL respectively. The search will begin with 10 selected candidate loci including INS, IGF1, IGF2, IGF1R, IGF2R, GH1, GH2, GHR, GHRF and SNRPN. The resulting IBD scored twin sample will be an enormously valuable resource which could be used to search for QTL's that influence ANY heritable quantitative trait. Extensive longitudinal data are already available in this population on multiple anthropometric, cardiovascular and biochemical variables which will be subjected to these analyses.