Understanding genetic risk for aneuploid conception

了解非整倍体受孕的遗传风险

基本信息

  • 批准号:
    10585662
  • 负责人:
  • 金额:
    $ 51.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-12-15 至 2028-04-30
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Because infertility is a growing public health problem, it is imperative that we understand the basic mechanisms and identify the genetic risk factors that give rise to this disease. The most common genetic abnormality that causes miscarriage is aneuploidy, an embryo with an improper number of chromosomes. Although increased risk of aneuploidy is strongly correlated with increasing maternal age, significant variation exists in aneuploidy rates at any given age, making age alone an inadequate biomarker for the risk of producing an aneuploid conception. Therefore, we hypothesize that women who produce higher than average levels of preimplantation stage aneuploidy at a given age possess causal variants in genes which predispose them to an early risk of producing an aneuploid conception. To test this hypothesis, we will develop methods to identify causal genes using low-coverage whole genome sequences obtained from blastocysts that underwent preimplantation genetic testing for aneuploidy (PGT-A). PGT-A sequencing is common for clinical care to guide single euploid embryo transfer, and therefore there is an abundance of sequences to analyze. Success in method development will likely have far reaching utility in enabling clinics to conduct their own genetics-based evaluations. Candidate genes identified by PGT-A analysis in this project and from previously analyzed datasets will be rapidly tested and validated for causation by using worm and fly model organisms. High-ranking candidates, and candidates without model organism homologs, will undergo one final validation pass in a mouse oocyte in vitro system, before creating mouse models that harbor the genetic variant of interest for in vivo studies that are not possible to conduct in humans. These approaches will shed light on the molecular mechanisms that control meiotic chromosome segregation in female gametes. Ultimately, this study could lead to the identification of maternal genetic markers for risk of producing an aneuploid conception and help avoid infertility by empowering women with necessary and personalized information to better preserve their individual fertility.
项目总结/文摘

项目成果

期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sirtuins in female meiosis and in reproductive longevity.
Mathematical modeling of human oocyte aneuploidy.
人类卵母细胞非整倍性的数学模型。
Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.
  • DOI:
    10.1038/s41467-021-25028-1
  • 发表时间:
    2021-08-18
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Singh P;Fragoza R;Blengini CS;Tran TN;Pannafino G;Al-Sweel N;Schimenti KJ;Schindler K;Alani EA;Yu H;Schimenti JC
  • 通讯作者:
    Schimenti JC
Analysis of DNA variants in miRNAs and miRNA 3'UTR binding sites in female infertility patients.
Meiosis interrupted: the genetics of female infertility via meiotic failure.
减数分裂中断:女性不育症通过减数分裂衰竭的遗传学。
  • DOI:
    10.1530/rep-20-0422
  • 发表时间:
    2021-03
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Biswas L;Tyc K;El Yakoubi W;Morgan K;Xing J;Schindler K
  • 通讯作者:
    Schindler K
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Karen A Schindler其他文献

Karen A Schindler的其他文献

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{{ truncateString('Karen A Schindler', 18)}}的其他基金

Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10683357
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10332058
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10455188
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10457384
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis (Equipment Administrative Supplement)
女性减数分裂过程中控制染色体分离的信号机制(设备管理补充)
  • 批准号:
    10405164
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10581965
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10682324
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10265406
  • 财政年份:
    2020
  • 资助金额:
    $ 51.98万
  • 项目类别:
Association of the Maternal Exome with Risk of an Aneuploid Conception
母体外显子组与非整倍体受孕风险的关联
  • 批准号:
    10307609
  • 财政年份:
    2017
  • 资助金额:
    $ 51.98万
  • 项目类别:
Association of the Maternal Exome with Risk of an Aneuploid Conception
母体外显子组与非整倍体受孕风险的关联
  • 批准号:
    10063883
  • 财政年份:
    2017
  • 资助金额:
    $ 51.98万
  • 项目类别:

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