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对定性和定量性状进行完整的多点同胞对分析。

Complete multipoint sib-pair analysis of qualitative and quantitative traits.

作者信息

Kruglyak L, Lander E S

机构信息

Whitehead Institute for Biomedical Research, Cambridge, MA 02142-1479, USA.

出版信息

Am J Hum Genet. 1995 Aug;57(2):439-54.

Abstract

Sib-pair analysis is an increasingly important tool for genetic dissection of complex traits. Current methods for sib-pair analysis are primarily based on studying individual genetic markers one at a time and thus fail to use the full inheritance information provided by multipoint linkage analysis. In this paper, we describe how to extract the complete multipoint inheritance information for each sib pair. We then describe methods that use this information to map loci affecting traits, thereby providing a unified approach to both qualitative and quantitative traits. Specifically, complete multipoint approaches are presented for (1) exclusion mapping of qualitative traits; (2) maximum-likelihood mapping of qualitative traits; (3) information-content mapping, showing the extent to which all inheritance information has been extracted at each location in the genome; and (4) quantitative-trait mapping, by two parametric methods and one nonparametric method. In addition, we explore the effects of marker density, marker polymorphism, and availability of parents on the information content of a study. We have implemented the analysis methods in a new computer package, MAPMAKER/SIBS. With this computer package, complete multipoint analysis with dozens of markers in hundreds of sib pairs can be carried out in minutes.

摘要

同胞对分析是复杂性状基因剖析中日益重要的工具。当前的同胞对分析方法主要基于逐个研究单个遗传标记,因此未能充分利用多点连锁分析提供的完整遗传信息。在本文中,我们描述了如何为每个同胞对提取完整的多点遗传信息。然后,我们描述了利用这些信息定位影响性状的基因座的方法,从而为定性和定量性状提供了统一的方法。具体而言,我们提出了完整的多点方法用于:(1)定性性状的排除定位;(2)定性性状的最大似然定位;(3)信息含量定位,显示在基因组每个位置提取所有遗传信息的程度;以及(4)通过两种参数方法和一种非参数方法进行数量性状定位。此外,我们探讨了标记密度、标记多态性以及父母的可用性对研究信息含量的影响。我们已在一个新的计算机软件包MAPMAKER/SIBS中实现了这些分析方法。使用这个计算机软件包,在几分钟内就可以对数百个同胞对中的数十个标记进行完整的多点分析。

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