Abstract
Several authors have proposed algorithms to detect Mendelian errors in human genetic linkage data. Most currently available methods use likelihood-based methods on multiplex family data to identify typing or pedigree errors. These algorithms cannot be applied in many sib-pair collections, because of lack of parental-genotype information. Nonetheless, misspecifying the relationships between individuals has serious consequences for sib-pair linkage studies: false relationships bias the statistics designed to identify linkage with disease phenotypes. To test the hypothesis that two individuals are sibs, we propose a test statistic based on the summation, over a large number of genetic markers, of the number of alleles shared identical by state by a pair of individuals, for each marker. The test statistic has an approximately normal distribution under the null hypothesis, and extreme negative values correspond to nonsib pairs. Power and significance studies show that the test statistic calculated by use of 50 unlinked markers has 96% power to detect half-sibs and has 100% power to detect unrelated individuals as not full-sib pairs, with a 5% false-positive rate. Furthermore, extreme positive values of the test statistic identify sibs as MZ twins.
Full Text
The Full Text of this article is available as a PDF (287.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boehnke M., Cox N. J. Accurate inference of relationships in sib-pair linkage studies. Am J Hum Genet. 1997 Aug;61(2):423–429. doi: 10.1086/514862. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buetow K. H. Influence of aberrant observations on high-resolution linkage analysis outcomes. Am J Hum Genet. 1991 Nov;49(5):985–994. [PMC free article] [PubMed] [Google Scholar]
- Ehm M. G., Kimmel M., Cottingham R. W., Jr Error detection for genetic data, using likelihood methods. Am J Hum Genet. 1996 Jan;58(1):225–234. [PMC free article] [PubMed] [Google Scholar]
- Hodge S. E. The information contained in multiple sibling pairs. Genet Epidemiol. 1984;1(2):109–122. doi: 10.1002/gepi.1370010203. [DOI] [PubMed] [Google Scholar]
- Lange K. A test statistic for the affected-sib-set method. Ann Hum Genet. 1986 Jul;50(Pt 3):283–290. doi: 10.1111/j.1469-1809.1986.tb01049.x. [DOI] [PubMed] [Google Scholar]
- Lathrop G. M., Hooper A. B., Huntsman J. W., Ward R. H. Evaluating pedigree data. I. The estimation of pedigree error in the presence of marker mistyping. Am J Hum Genet. 1983 Mar;35(2):241–262. [PMC free article] [PubMed] [Google Scholar]
- Ott J. Computer-simulation methods in human linkage analysis. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4175–4178. doi: 10.1073/pnas.86.11.4175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stringham H. M., Boehnke M. Identifying marker typing incompatibilities in linkage analysis. Am J Hum Genet. 1996 Oct;59(4):946–950. [PMC free article] [PubMed] [Google Scholar]