A method for haplotype inference in general pedigrees without recombination  

作　　者：WANG ChunKao WANG ZhiPeng QIU XiaoTian ZHANG Qin 

机构地区：[1]Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, State Key Laboratories of AgroBiotechnology, College of Animal Science and Technology, China Agricultural University, Beijing 100094, China

出　　处：《Chinese Science Bulletin》2007年第4期471-476,共6页

基　　金：Supported by the National Natural Science Foundation of China (Grant No. 30430500);the National Key Basic Research Program (Grant No. 2006CB102104)

摘　　要：The abundance of single nucleotide polymorphisms (SNPs) makes the haplotype-based method instead of single-maker-oriented method the main approach to association studies on QTL mapping. The key problem in haploptype-based method is how to reconstruct haplotypes from genotype data. Directly assaying haplotypes in diploid individuals by experimental methods is too expensive, therefore the in silico haplotyping-determination methods are the major choice at the present. This paper presents a rapid and reliable algorithm for haplotype reconstruction for tightly linked SNPs in general pedigrees. It is based on six rules and consists of three steps. First, the parental origins of alleles in offspring are assigned conditional on genotypes in parent-offspring trios; second, the redundant haplotypes are eliminated based on the six rules; and finally, the most likely haplotype combinations are chosen via maximum likelihood method. Our method was verified and compared with PEDPHASE by simulated data with different pedigree sizes, numbers of loci, and proportions of missing genotypes. The result shows that our algorithm was superior to PEDPHASE in terms of computing time and accuracy of haplotype estimation. The computing time for 100 runs was 10―15 times less and the accuracy was 4%―10% higher than PEDPHASE. The result also indicates that our method was very robust and was hardly affected by pedigree size, number of loci, and proportion of missing genotypes.The abundance of single nucleotide polymorphisms （SNPs） makes the haplotype-based method instead of single-maker-oriented method the main approach to association studies on QTL mapping. The key problem in haploptype-based method is how to reconstruct haplotypes from genotype data. Directly assaying haplotypes in diploid individuals by experimental methods is too expensive, therefore the in silico haplotyping-determination methods are the major choice at the present. This paper presents a rapid and reliable algorithm for haplotype reconstruction for tightly linked SNPs in general pedigrees. It is based on six rules and consists of three steps. First, the parental origins of alleles in offspring are assigned conditional on genotypes in parent-offspring trios; second, the redundant haplotypes are eliminated based on the six rules; and finally, the most likely haplotype combinations are chosen via maximum likelihood method. Our method was verified and compared with PEDPHASE by simulated data with different pedigree sizes, numbers of loci, and proportions of missing genotypes. The result shows that our algorithm was superior to PEDPHASE in terms of computing time and accuracy of haplotype estimation. The computing time for 100 runs was 10-15 times less and the accuracy was 4%-10% higher than PEDPHASE. The result also indicates that our method was very robust and was hardly affected by pedigree size, number of loci, and proportion of missing genotypes.

关 键 词：单核多态性 单倍型干扰 谱系 非重组 计算方法 QTL 

分 类 号：Q343.22[生物学—遗传学]