Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al.  that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband’s sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband’s married-in-grandparents in the analysis.
© 2007 S. Karger AG, Basel
- False positives
- Linkage analysis
- Linkage disequilibrium (LD)
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Dr. Suzanne M. Leal
Baylor College of Medicine, Department of Molecular and Human Genetics
One Baylor Plaza, Alkek Building N1619.01
Houston, TX 77030 (USA)
Tel. +1 713 798 4001, Fax +1 713 798 5741, E-Mail firstname.lastname@example.org
Received: June 19, 2007
Accepted after revision: July 30, 2007
Published online: December 11, 2007
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 1, Number of References : 27
Human Heredity (International Journal of Human and Medical Genetics)
Vol. 65, No. 4, Year 2008 (Cover Date: January 2008)
Journal Editor: Devoto, M. (Philadelphia, Pa.)
ISSN: 0001–5652 (Print), eISSN: 1423–0062 (Online)
For additional information: http://www.karger.com/HHE
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