Linkage disequilibrium mapping in trisomic populations: Analytical approaches and an application to congenital heart defects in Down syndrome
Linkage disequilibrium mapping in trisomic populations: Analytical approaches and an application to congenital heart defects in Down syndrome
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DOI：
10.1002/gepi.20019
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发表时间：
2004-11-01
影响因子：
2.1
通讯作者：
Sherman, SL
中科院分区：
文献类型：
--
作者：
Kerstann, KF;Feingold, E;Sherman, SL
许多与三体性相关的出生缺陷表现出可变的表达性和不完全的表达性。这种变异性表明，它是等位基因变异，而不是简单地存在一个额外的染色体，导致某些三体相关的出生缺陷的发展。有了适当的工具，人们可以使用三体群体来识别参与特定出生缺陷发展的基因。如果缺陷在三体群体中过度表现，则三体群体可能优于正常群体。或者，人们可以将三体群体视为“模型系统”，以提供对正常和异常胚胎发育方面的见解。标准的二体连锁不平衡作图方法需要进行调整，以解释三体个体中额外遗传物质的存在。我们提出了一种方法，在三体人口中的可变表型的连锁不平衡映射，充分占额外的等位基因和非独立遗传的模式。我们建立了必要的实验室方法和统计工具，在三体人群中进行关联研究。作为一个例子，我们已经将这些工具应用于唐氏综合征相关先天性心脏病的初步研究。(C)2004 Wiley-Liss，Inc.
Many of the birth defects associated with trisomy exhibit both variable expressivity and incomplete penetrance. This variability suggests that it is allelic variation and not simply the presence of an additional chromosome that leads to the development of certain trisomy-associated birth defects. With the proper tools, one may use trisomic populations to identify genes involved in the development of specific birth defects. A trisomic population may be advantageous over a normal population if the defect is over-represented in the trisomic population. Alternatively, one can view the trisomic populations as a "model system" to offer insight into aspects of both normal and abnormal embryonic development. Standard disomic linkage disequilibrium mapping approaches need to be adjusted to account for the presence of the additional genetic material in the trisomic individuals. We present an approach for linkage disequilibrium mapping of variable phenotypes in a trisomic population that adequately accounts for the additional alleles and the pattern of non-independent inheritance. We establish the laboratory methods and statistical tools necessary to conduct an association study in a trisomic population. As an example, we have applied these tools to a pilot study of Down syndrome-associated congenital heart defects. (C) 2004 Wiley-Liss, Inc.