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多位点连锁分析中重组率和干涉系数的联合估计

Joint estimation of recombination fractions and interference coefficients in multilocus linkage analysis.

作者信息

Zhao L P, Thompson E, Prentice R

机构信息

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle.

出版信息

Am J Hum Genet. 1990 Aug;47(2):255-65.

Abstract

Estimation of recombination fractions and interference coefficients is of importance in multilocus linkage analysis. With the development of molecular genetic technologies such as RFLP, multilocus data are readily available to researchers. Several methods have been developed to analyze such data, and each performs well under restrictive conditions. The present paper proposes a method based on a multiplicative model and maximum-likelihood estimation of recombination fractions and interference coefficients. The estimators are consistent regardless of the model assumptions and are efficient if the model is a good approximation. The estimators are tractable even when there are incomplete observations. Furthermore, the interference between nonadjacent chromosomal regions or those among three chromosomal regions can be modeled and tested by a simple Z-test. The proposed method was applied to linkage analysis of four-locus data obtained from Drosophila and that of seven-locus data obtained again from Drosophila. Reanalysis of the first example revealed that there is interference between chromosomal regions 2 and 3. Analysis of the second example suggested that there is triple interference as well as pairwise interference between nonadjacent chromosomal regions; the genetic interpretation of these findings remains to be developed.

摘要

在多位点连锁分析中,重组率和干涉系数的估计非常重要。随着诸如限制性片段长度多态性(RFLP)等分子遗传技术的发展,研究人员很容易获得多位点数据。已经开发了几种方法来分析此类数据,并且每种方法在特定条件下都表现良好。本文提出了一种基于乘法模型以及重组率和干涉系数的最大似然估计的方法。无论模型假设如何,估计量都是一致的,并且如果模型是一个很好的近似,则估计量是有效的。即使存在不完整的观测值,估计量也是易于处理的。此外,非相邻染色体区域之间或三个染色体区域之间的干涉可以通过一个简单的Z检验进行建模和检验。所提出的方法应用于从果蝇获得的四位点数据的连锁分析以及再次从果蝇获得的七位点数据的连锁分析。对第一个例子的重新分析表明,染色体区域2和3之间存在干涉。对第二个例子的分析表明,非相邻染色体区域之间存在三重干涉以及成对干涉;这些发现的遗传学解释仍有待进一步研究。

引用本文的文献

1
The robustness of recombination frequency estimates in intercrosses with dominant markers.
Genetics. 1994 Jun;137(2):589-96. doi: 10.1093/genetics/137.2.589.
2
Detection of genetic interference: simulation studies and mouse data.
Genetics. 1994 Mar;136(3):1217-26. doi: 10.1093/genetics/136.3.1217.

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