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The effect of linkage disequilibrium on linkage analysis of incomplete pedigrees

Levinson, D. F. and Holmans, Peter Alan 2005. The effect of linkage disequilibrium on linkage analysis of incomplete pedigrees. BMC Genetics 6 (1) , S6-S6. 10.1186/1471-2156-6-S1-S6

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Abstract

Dense SNP maps can be highly informative for linkage studies. But when parental genotypes are missing, multipoint linkage scores can be inflated in regions with substantial marker-marker linkage disequilibrium (LD). Such regions were observed in the Affymetrix SNP genotypes for the Genetic Analysis Workshop 14 (GAW14) Collaborative Study on the Genetics of Alcoholism (COGA) dataset, providing an opportunity to test a novel simulation strategy for studying this problem. First, an inheritance vector (with or without linkage present) is simulated for each replicate, i.e., locations of recombinations and transmission of parental chromosomes are determined for each meiosis. Then, two sets of founder haplotypes are superimposed onto the inheritance vector: one set that is inferred from the actual data and which contains the pattern of LD; and one set created by randomly selecting parental alleles based on the known allele frequencies, with no correlation (LD) between markers. Applying this strategy to a map of 176 SNPs (66 Mb of chromosome 7) for 100 replicates of 116 sibling pairs, significant inflation of multipoint linkage scores was observed in regions of high LD when parental genotypes were set to missing, with no linkage present. Similar inflation was observed in analyses of the COGA data for these affected sib pairs with parental genotypes set to missing, but not after reducing the marker map until r2 between any pair of markers was

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: BioMed Central
ISSN: 1471-2156
Date of First Compliant Deposit: 20 August 2018
Last Modified: 02 May 2019 12:54
URI: http://orca.cardiff.ac.uk/id/eprint/83298

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