The impact of genotyping error on haplotype reconstruction and frequency estimation

Kirk, Katherine M. and Cardon, Lon R. (2002) The impact of genotyping error on haplotype reconstruction and frequency estimation. European Journal of Human Genetics, 10 10: 616-622. doi:10.1038/sj.ejhg.5200855

Author Kirk, Katherine M.
Cardon, Lon R.
Title The impact of genotyping error on haplotype reconstruction and frequency estimation
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
Publication date 2002-10
Sub-type Article (original research)
DOI 10.1038/sj.ejhg.5200855
Volume 10
Issue 10
Start page 616
End page 622
Total pages 7
Place of publication London, U.K.
Publisher Nature Publishing Group
Collection year 2002
Language eng
Subject C1
270200 Genetics
730107 Inherited diseases (incl. gene therapy)
0604 Genetics
Abstract The choice of genotyping families vs unrelated individuals is a critical factor in any large-scale linkage disequilibrium (LD) study. The use of unrelated individuals for such studies is promising, but in contrast to family designs, unrelated samples do not facilitate detection of genotyping errors, which have been shown to be of great importance for LD and linkage studies and may be even more important in genotyping collaborations across laboratories. Here we employ some of the most commonly-used analysis methods to examine the relative accuracy of haplotype estimation using families vs unrelateds in the presence of genotyping error. The results suggest that even slight amounts of genotyping error can significantly decrease haplotype frequency and reconstruction accuracy, that the ability to detect such errors in large families is essential when the number/complexity of haplotypes is high (low LD/common alleles). In contrast, in situations of low haplotype complexity (high LD and/or many rare alleles) unrelated individuals offer such a high degree of accuracy that there is little reason for less efficient family designs. Moreover, parent-child trios, which comprise the most popular family design and the most efficient in terms of the number of founder chromosomes per genotype but which contain little information for error detection, offer little or no gain over unrelated samples in nearly all cases, and thus do not seem a useful sampling compromise between unrelated individuals and large families. The implications of these results are discussed in the context of large-scale LD mapping projects such as the proposed genome-wide haplotype map.
Keyword Biochemistry & Molecular Biology
Genetics & Heredity
Genotyping Error
Linkage Disequilibrium
Single-nucleotide Polymorphisms
Human Genome
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 55 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 61 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 14 Aug 2007, 17:53:12 EST