Combining information within and between pedigrees for mapping complex traits (original) (raw)

. 1997 Apr;60(4):979–992.

Abstract

This paper is concerned with efficient strategies for gene mapping using pedigrees containing small numbers of affecteds and identity-by-descent data from closely spaced markers throughout the genome. Particular attention is paid to additive traits involving phenocopies and/or locus heterogeneity. For a sample of pedigrees containing a particular configuration of affecteds, e.g., pairs of siblings together with a first cousin, we use a likelihood analysis to find 1-df statistics that are very efficient over a broad range of penetrances and allele frequencies. We identify configurations of affecteds that are particularly powerful for detecting linkage, and we show how pedigrees containing different numbers and configurations of affecteds can be efficiently combined in an overall test statistic.

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Selected References

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  1. Blackwelder W. C., Elston R. C. A comparison of sib-pair linkage tests for disease susceptibility loci. Genet Epidemiol. 1985;2(1):85–97. doi: 10.1002/gepi.1370020109. [DOI] [PubMed] [Google Scholar]
  2. Dupuis J., Brown P. O., Siegmund D. Statistical methods for linkage analysis of complex traits from high-resolution maps of identity by descent. Genetics. 1995 Jun;140(2):843–856. doi: 10.1093/genetics/140.2.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Feingold E., Brown P. O., Siegmund D. Gaussian models for genetic linkage analysis using complete high-resolution maps of identity by descent. Am J Hum Genet. 1993 Jul;53(1):234–251. [PMC free article] [PubMed] [Google Scholar]
  4. James J. W. Frequency in relatives for an all-or-none trait. Ann Hum Genet. 1971 Jul;35(1):47–49. doi: 10.1111/j.1469-1809.1956.tb01377.x. [DOI] [PubMed] [Google Scholar]
  5. Lander E. S., Botstein D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989 Jan;121(1):185–199. doi: 10.1093/genetics/121.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lander E. S., Schork N. J. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. doi: 10.1126/science.8091226. [DOI] [PubMed] [Google Scholar]
  7. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  8. Nelson S. F., McCusker J. H., Sander M. A., Kee Y., Modrich P., Brown P. O. Genomic mismatch scanning: a new approach to genetic linkage mapping. Nat Genet. 1993 May;4(1):11–18. doi: 10.1038/ng0593-11. [DOI] [PubMed] [Google Scholar]
  9. Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990 Feb;46(2):222–228. [PMC free article] [PubMed] [Google Scholar]
  10. Rogus J. J., Krolewski A. S. Using discordant sib pairs to map loci for qualitative traits with high sibling recurrence risk. Am J Hum Genet. 1996 Dec;59(6):1376–1381. [PMC free article] [PubMed] [Google Scholar]
  11. Schwab S. G., Albus M., Hallmayer J., Hönig S., Borrmann M., Lichtermann D., Ebstein R. P., Ackenheil M., Lerer B., Risch N. Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis. Nat Genet. 1995 Nov;11(3):325–327. doi: 10.1038/ng1195-325. [DOI] [PubMed] [Google Scholar]
  12. Sribney W. M., Swift M. Power of sib-pair and sib-trio linkage analysis with assortative mating and multiple disease loci. Am J Hum Genet. 1992 Oct;51(4):773–784. [PMC free article] [PubMed] [Google Scholar]
  13. Thomas A., Skolnick M. H., Lewis C. M. Genomic mismatch scanning in pedigrees. IMA J Math Appl Med Biol. 1994;11(1):1–16. doi: 10.1093/imammb/11.1.1. [DOI] [PubMed] [Google Scholar]
  14. Weeks D. E., Lange K. A multilocus extension of the affected-pedigree-member method of linkage analysis. Am J Hum Genet. 1992 Apr;50(4):859–868. [PMC free article] [PubMed] [Google Scholar]
  15. Whittemore A. S., Halpern J. A class of tests for linkage using affected pedigree members. Biometrics. 1994 Mar;50(1):118–127. [PubMed] [Google Scholar]