POPULATION STRUCTURE OF GENETIC VARIATION IN PREGNANCY

研究摘要 项目I的总体目标是确定 妊娠和早产的母体-胎盘-胎儿（MPF）内分泌途径中的候选基因 出生虽然影响早产的确切遗传因素尚未确定， 遗传学的重要性表现为家族聚集性、种族/民族间患病率的差异 组和分子遗传学研究，已确定与DMA多态性的显着关联 在分娩的候选基因中。以前的研究表明， 种族/族裔群体之间的早产，可能是由于遗传和环境因素。项目我 将对比三个主要种族/民族（非洲人）中每一个的16个候选基因的变异模式 美国人、墨西哥裔西班牙人和非西班牙裔白人）。我们将识别序列变异 （SNPs），并通过对三个种族/民族中的每一个进行重测序， 分别含有母本和父本染色体的单倍体细胞系（分子单倍型）。的 我们在项目I中发现的SNP将由核心C在1,200对母子中进行基因分型，以供后续研究。 群体遗传分析。具体目标是：目标1：对母胎胎盘组织中的16个候选基因进行重测序， 胎儿（MPF）神经内分泌途径，以确定和表征DMA的分布 序列变异（SNP）内和代表三个地方的个体样本之间 人口：非洲裔美国人，墨西哥裔西班牙人和非西班牙裔白人。目标2：模型和测试 关于16个候选基因的变异结构的假设，以确定哪些等位基因， 单倍型，以及哪些基因的基因型在三个种族/民族中的哪一个内和哪一个之间变化 样品美国早产率种族/族裔差异的根本原因 各国都不太了解。我们和其他人最近发现了显著的种族/民族差异 在妊娠过程中母体-胎盘-胎儿神经内分泌系统的生物学中。通过 确定三个主要种族/民族群体的遗传变异的人口结构，该项目 将对我们理解所观察到的种族/民族 生物学和临床结果（早产）的差异反映了遗传变异的差异， 由于相同基因和变体的表达改变而产生的差异， 环境条件/触发因素的种族/民族差异。

ABSTRACT OF RESEARCH PLAN The overall goal of Project I is to determine the extent and distribution of sequence variation in candidate genes in the maternal-placental-fetal (MPF) endocrine pathway of pregnancy and premature birth. Although the precise genetic factors that influence premature birth have not yet been identified, the importance of genetics is indicated by familial aggregation, differences in prevalence among racial/ethnic groups, and molecular genetic studies that have identified significant associations with DMA polymorphisms in candidate genes of parturition. Previous studies have shown large disparities in the prevalence of premature birth across racial/ethnic groups, likely due to both genetic and environmental factors. Project I will contrast patterns of variation in 16 candidate genes for each of three major racial/ethnic groups (African Americans, Hispanics of Mexican Origin, and non-Hispanic Whites). We will identify sequence variations (SNPs) and directly determine SNP haplotypes for each of three racial/ethnic groups by resequencing in haploid cell lines that separately contain maternal and paternal chromosomes (molecular haplotyping). The SNPs we identify in Project I will be genotyped in the 1,200 mother-child pairs by Core C for subsequent population genetic analyses. The specific aims are: Aim 1: Resequence 16 candidate genes in the maternalplacental- fetal (MPF) neuroendocrine pathway to identify and characterize the distribution of DMA sequence variations (SNPs) within and among samples of individuals representative of three local populations: African-American, Hispanic of Mexican origin, and non-Hispanic Whites. Aim 2: Model and test hypotheses about the structure of the variation in the 16 candidate genes to establish which alleles, which haplotypes, and which genotypes of which genes vary within and between which of the three racial/ethnic samples. The underlying causes of racial/ethnic disparities in the prevalence of premature birth in the United States are not well-understood. We and others have recently discovered significant racial/ethnic differences in the biology of the maternal-placental-fetal neuroendocrine system over the course of gestation. By determining the population structure of genetic variation in the three major racial/ethnic groups, this project will make an important contribution to our understanding of the extent to which the observed racial/ethnic differences in biology and clinical outcome (premature birth) reflect differences in genetic variation or differences that arise from altered expression of the same genes and variants as a consequence of racial/ethnic differences in environmental conditions/triggers.