Accuracy of haplotype estimation in a region of low linkage disequilibrium Public Deposited

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  • North, Kari
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Martin, Lisa J
    • Other Affiliation: Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  • Williams, Jeff T
    • Other Affiliation: Department of Genetics, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA
  • Avery, Christy
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Abstract We compared the accuracy of haplotype inferences at a 6 Mb region on chromosome 7 where significant linkage between a brain oscillation phenotype and a cholinergic muscarinic receptor gene was previously reported. Individual haplotype assignments and haplotype frequencies were estimated using 5, 10, and 14 consecutive Illumina single-nucleotide polymorphisms (SNPs) within the 1-LOD unit support interval of the chromosome 7 linkage peak. Initially, haplotypes were constructed incorporating phase information provided by relatives using the pedigree analysis package MERLIN. Population-based haplotypes were inferred using the haplotype estimation software HAPLO.STATS and PHASE, using unrelated individuals. The 14 SNPs within this region exhibited markedly low linkage disequilibrium, and the average D' estimate between SNPs was 0.18 (range: 0.01–0.97). In comparison to the family-based haplotypes calculated in MERLIN, the computational inferences of individual haplotype assignments were most accurate when considering 5 consecutive SNPs, but decayed dramatically when considering 10 or 14 SNPs in both PHASE and HAPLO.STATS. When comparing the two haplotype inference methods, both PHASE and HAPLO.STATS performed poorly. These analyses underscore the difficulties of haplotype estimation in the presence of low linkage disequilibrium and stress the importance of careful consideration of confidence measures when using estimated haplotype frequencies and individual assignments in biomedical research.
Date of publication
  • doi:10.1186/1471-2156-6-S1-S80
Resource type
  • Article
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  • In Copyright
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  • Christy L Avery et al.; licensee BioMed Central Ltd.
  • English
Is the article or chapter peer-reviewed?
  • Yes
Bibliographic citation
  • BMC Genetics. 2005 Dec 30;6(Suppl 1):S80
  • Open Access
  • BioMed Central Ltd

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