• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Assessing maternal, offspring and maternal-fetal genotype incompatibility effects at a highly-polymorphic locus.
【24h】

Assessing maternal, offspring and maternal-fetal genotype incompatibility effects at a highly-polymorphic locus.

机译：在高度多态的基因座评估母体，后代和母胎基因型不相容性的影响。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To elucidate the etiology of a disease that may have an origin during fetal development, maternal genetic effects, offspring genetic effects and their interaction effects should each be considered. The maternal-fetal genotype (MFG) incompatibility test has been proposed to detect whether certain combinations of genes for a mother and her offspring are associated with disease risk in the offspring. The development of the MFG test focused predominantly on a bi-allelic locus. However, the study can be especially difficult at a highly-polymorphic locus, for example, HLA-DRB1, where two issues often arise. When the gene under study can influence another competing phenotype, e.g., offspring viability, the genetic association with the disease may be confounded or lead to incorrect conclusions. When some family genotype data are missing, the large numbers of alleles and their various modes of action at a multi-allelic locus make the efficient use of the information provided by incomplete families difficult.; Using nuclear family genotype data composed of the parents and at least one affected offspring, I propose a v-MFG test that can assess genetic effects produced by a gene on two phenotypes simultaneously. Hence the v-MFG test adjusts the possible bias resulting from confounding of viability in disease association studies. I also describe an identical-by-state (IBS) algorithm that utilizes the IBS-types, defined from combined information of family genotypes, to accommodate incomplete families into the analysis.; Through computer simulations, I show that the v-MFG test is sufficiently powerful to detect genetic association with a disease when viability is reduced. It also produces accurate genetic effect estimates for disease as well as for viability under population stratification. The v-MFG test is applied on a real data set to evaluate an MFG incompatibility effect on rheumatoid arthritis. My simulations also show that the IBS algorithm is useful to utilize incomplete families in studies at a multi-allelic locus. The IBS-types make it feasible to evaluate non-Mendelian genetic effects in one model, and the tests using IBS-types is robust to population stratification. The incomplete families can be incorporated to recover power information that would otherwise be lost and thereby to enhance statistical power.
机译：为了阐明在胎儿发育过程中可能起源的疾病的病因，应分别考虑母体遗传效应，后代遗传效应及其相互作用。已经提出了母胎基因型（MFG）不相容性测试来检测母亲及其后代的某些基因组合是否与后代的疾病风险相关。 MFG测试的发展主要集中在双等位基因座。但是，对于高度多态的基因座，例如HLA-DRB1，经常会出现两个问题，因此研究可能特别困难。当所研究的基因可以影响另一种竞争表型（例如后代生存力）时，与该疾病的遗传关联可能会混淆或导致错误的结论。当缺少一些家庭基因型数据时，在一个多等位基因位点的大量等位基因及其不同的作用方式使得难以有效利用不完整家庭提供的信息。我使用由父母和至少一个受影响的后代组成的核心家庭基因型数据，提出了一种v-MFG检验，该检验可以评估一个基因同时对两种表型产生的遗传效应。因此，v-MFG测试可调整疾病关联研究中因生存能力混淆而导致的可能偏倚。我还描述了一种状态相同（IBS）算法，该算法利用从家庭基因型的组合信息中定义的IBS类型，将不完整的家庭纳入分析。通过计算机仿真，我证明了v-MFG测试功能强大，足以检测出生存力降低时与疾病的遗传关联。它还可以为疾病以及人口分层下的生存力提供准确的遗传效应估计。 v-MFG测试应用于真实数据集，以评估MFG对类风湿关节炎的不相容作用。我的模拟还表明，IBS算法对于在多等位基因座的研究中利用不完整的家族很有用。 IBS类型使在一个模型中评估非孟德尔遗传效应变得可行，并且使用IBS类型的测试对人口分层具有鲁棒性。不完整的族可以合并以恢复原本会丢失的功效信息，从而增强统计功效。

著录项

  • 作者

    Hsieh, Hsin-Ju.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Biology Biostatistics.; Biology Genetics.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 98 p.
  • 总页数 98
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物数学方法;遗传学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号