权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Genetic Studies of Fertility in the Hutterites

哈特人生育力的分子遗传学研究

基本信息

批准号：
8116587
负责人：
Carole Ober
金额：
$ 25.73万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-10-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8116587
关键词：
Alleles Architecture Birth Chromosome Mapping Chromosomes Complex Contraceptive methods Couples Data European Family Female Fertility Fertility Study Fibroblast Growth Factor Receptor 2 Gene Cluster Genes Genetic Genotype Goals Grant HLA G antigen Habitual Abortion Haplotypes Heritability ITGAM gene In Vitro Individual Differences Infertility Interferons Lead Link Maps Marriage Measures Methods Mitochondria Modeling Molecular Genetics Pathway interactions Phenotype Population Pregnancy Outcome Pregnancy loss Process Prospective Studies Recurrence Religion and Spirituality Reproduction Research Infrastructure Research Personnel Sex Chromosomes Short Tandem Repeat Polymorphism Single Nucleotide Polymorphism Single Nucleotide Polymorphism Map Testing Variant Woman X Chromosome Y Chromosome analytical tool computing resources genetic pedigree genome wide association study genome-wide genome-wide linkage hutterite improved male meetings men novel protocadherin 10 reproductive trait

项目摘要

DESCRIPTION (provided by applicant): Over the past -25 years, we have studied reproductive phenotypes in >500 Hutterite couples. Although our previous focus was on HLA region genes, our studies also suggested that non-HLA genes influencing fertility were also segregating in the population. Thus, in this renewal application, we will continue to study the genetics of fertility in the Hutterites, but now use genome-wide approaches to identify novel genes. We propose to identify and characterize genes that contribute to female and male fertility, measured by the number of births per years of marriage, which are highly heritable traits in the Hutterites (66% heritability in females and 42% heritability in males). An initial genome-wide screen with ~1,500 markers already identified 5 novel genes (1 in females, 4 in males) that met criteria for genome-wide significance. In this application we propose to further characterize 4 of these potential fertility genes in Hutterite couples participating in a prospective study of pregnancy outcome (currently in it's 20th year) and in outbred populations (including women with recurrent pregnancy loss and infertility; and males with nonobstructive azoospermia). In addition, we propose to conduct genome-wide association studies of female and male fertility in the Hutterites using 500,000 SNPs to identify additional fertility genes, and then characterize those genes as well in the Hutterites and in outbred populations. These studies will largely utilize infrastructure (genotypes, phenotypes, computational resources) already available to us. Lastly, we propose to extend our mapping methods to include genes on non-autosomal chromosomes (X, Y, mitochondrial) and study the impact of genes on those chromosomes on fertility in women (X, mitochondrial) and in men (X, Y, mitochondrial). These studies have the potential to identify novel genes and pathways that influence fertility, and possibly infertility, and could lead to improved treatments for infertility or recurrent miscarriage, or to improved methods of contraception.

描述（由申请人提供）：在过去的25年里，我们研究了>500对哈特夫妇的生殖表型。虽然我们以前的重点是HLA区域基因，我们的研究也表明，非HLA基因影响生育力也分离的人口。因此，在这个更新的申请中，我们将继续研究哈特人生育力的遗传学，但现在使用全基因组方法来识别新基因。我们建议识别和表征有助于女性和男性生育力的基因，以婚姻中每年出生的数量来衡量，这些基因在哈特人中具有高度遗传性（女性遗传率为66%，男性遗传率为42%）。最初的全基因组筛选约1,500个标记已经确定了5个新基因（1个在女性中，4个在男性中），符合全基因组意义的标准。在本申请中，我们提出进一步表征参与妊娠结果的前瞻性研究（目前在其第20年）的哈特夫妇和远系繁殖群体（包括患有复发性妊娠丢失和不孕症的女性;以及患有非梗阻性无精子症的男性）中的这些潜在生育基因中的4个。此外，我们建议进行全基因组关联研究的女性和男性的生育能力在哈特派使用50万个SNP来识别额外的生育基因，然后表征这些基因以及在哈特派和远交人群。这些研究将在很大程度上利用我们现有的基础设施（基因型，表型，计算资源）。最后，我们建议将我们的映射方法扩展到包括非常染色体上的基因（X，Y，线粒体），并研究这些染色体上的基因对女性（X，线粒体）和男性（X，Y，线粒体）生育能力的影响。这些研究有可能确定影响生育力和可能的不孕症的新基因和途径，并可能导致改善不孕症或复发性流产的治疗方法，或改善避孕方法。

项目成果

期刊论文数量（81）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

PRIMAL: Fast and accurate pedigree-based imputation from sequence data in a founder population.

DOI：
10.1371/journal.pcbi.1004139
发表时间：
2015-03
期刊：
PLoS computational biology
影响因子：
4.3
作者：
Livne OE;Han L;Alkorta-Aranburu G;Wentworth-Sheilds W;Abney M;Ober C;Nicolae DL
通讯作者：
Nicolae DL

A robust test for assortative mating.

选型交配的稳健测试。