Multipoint linkage-disequilibrium-mapping approach based on the case-parent trio design.
Multipoint linkage-disequilibrium-mapping approach based on the case-parent trio design.
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DOI：
10.1086/319504
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发表时间：
2001-04
影响因子：
9.8
通讯作者：
Kung Yee Liang;Fang-Chi Hsu;T. Beaty;Kathleen C. Barnes
中科院分区：
文献类型：
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作者：
Kung Yee Liang;Fang-Chi Hsu;T. Beaty;Kathleen C. Barnes
在本研究中，我们提出了一种基于案例-亲本三重奏设计的多点方法，用于基因映射。我们首先推导了由几个遗传标记划分的染色体区域内任意位置的预期优先等位基因传播统计的表达式，用于从父母任一方到受影响的孩子的传播。除了不超过一个疾病基因位于标记所框区域的假设之外，在这一推导中不需要关于遗传机制的假设。当人们建立在这种表示的基础上时，最大化来自多个标记的遗传信息的方式就变得显而易见。该方法与流行的精细作图传输/不平衡测试（TDT）方法不同，具体体现在以下几个方面：首先，与 TDT 方法相比，所有标记都贡献信息，无论亲本在任何一个标记上是否是杂合的，并且在我们的方法中可以利用不完整的三重奏数据。其次，我们不是单独对每个标记执行 TDT，而是提出一个单一的检验统计量，该检验统计量遵循 1 df 的 chi(2) 分布，在与该区域没有连锁或连锁不平衡的零假设下。第三，在存在关联证据的情况下，我们提供了一种估计疾病位点位置及其采样不确定性的方法。我们用在巴巴多斯进行的一项哮喘家庭研究的数据来说明所提出的方法。
In the present study we propose a multipoint approach, for the mapping of genes, that is based on the case-parent trio design. We first derive an expression for the expected preferential-allele-transmission statistics for transmission, from either parent to an affected child, for an arbitrary location within a chromosomal region demarcated by several genetic markers. No assumption about genetic mechanism is needed in this derivation, beyond the assumption that no more than one disease gene lies in the region framed by the markers. When one builds on this representation, the way in which one may maximize the genetic information from multiple markers becomes obvious. This proposed method differs from the popular transmission/disequilibrium test (TDT) approach for fine mapping, in the following ways: First, in contrast with the TDT approach, all markers contribute information, regardless of whether the parents are heterozygous at any one marker, and incomplete trio data can be utilized in our approach. Second, rather than performing the TDT at each marker separately, we propose a single test statistic that follows a chi(2) distribution with 1 df, under the null hypothesis of no linkage or linkage disequilibrium to the region. Third, in the presence of linkage evidence, we offer a means to estimate the location of the disease locus along with its sampling uncertainty. We illustrate the proposed method with data from a family study of asthma, conducted in Barbados.