Linkage disequilibrium and gene mapping: an empirical least-squares approach - PubMed (original) (raw)
Linkage disequilibrium and gene mapping: an empirical least-squares approach
L C Lazzeroni. Am J Hum Genet. 1998 Jan.
Abstract
This paper proposes a novel approach for fine-scale mapping of disease genes that is based on the well-known linkage-disequilibrium parameter delta. Using a very simple, very general model, I show how delta can be interpreted in terms of identity-by-descent probabilities. The value of delta follows a piecewise curve along the chromosome, with the maximum occurring at the disease locus where the two pieces intersect. A semiparametric, multilocus approach is used to fit this nonlinear regression curve in order to estimate the gene location. Using the bootstrap to empirically estimate much of the probability model from the data avoids the need for many detailed population assumptions. One advantage of the approach is its use of the observed covariance structure of the data, which can be highly informative as to the gene location. I illustrate the method on the cystic fibrosis data of Kerem et al.
Similar articles
- Fieller's theorem and linkage disequilibrium mapping.
Cordell HJ, Elston RC. Cordell HJ, et al. Genet Epidemiol. 1999 Nov;17(4):237-52. doi: 10.1002/(SICI)1098-2272(199911)17:4<237::AID-GEPI1>3.0.CO;2-P. Genet Epidemiol. 1999. PMID: 10520208 - A comparison of linkage disequilibrium measures for fine-scale mapping.
Devlin B, Risch N. Devlin B, et al. Genomics. 1995 Sep 20;29(2):311-22. doi: 10.1006/geno.1995.9003. Genomics. 1995. PMID: 8666377 - Linkage disequilibrium mapping: the role of population history, size, and structure.
Chapman NH, Thompson EA. Chapman NH, et al. Adv Genet. 2001;42:413-37. doi: 10.1016/s0065-2660(01)42034-7. Adv Genet. 2001. PMID: 11037333 Review. - A chronology of fine-scale gene mapping by linkage disequilibrium.
Lazzeroni LC. Lazzeroni LC. Stat Methods Med Res. 2001 Feb;10(1):57-76. doi: 10.1177/096228020101000104. Stat Methods Med Res. 2001. PMID: 11329692 Review.
Cited by
- Improved power by use of a weighted score test for linkage disequilibrium mapping.
Wang T, Elston RC. Wang T, et al. Am J Hum Genet. 2007 Feb;80(2):353-60. doi: 10.1086/511312. Epub 2006 Dec 21. Am J Hum Genet. 2007. PMID: 17236140 Free PMC article. - Association mapping of complex trait loci with context-dependent effects and unknown context variable.
Sillanpää MJ, Bhattacharjee M. Sillanpää MJ, et al. Genetics. 2006 Nov;174(3):1597-611. doi: 10.1534/genetics.106.061275. Epub 2006 Oct 8. Genetics. 2006. PMID: 17028339 Free PMC article. - On the use of haplotype phylogeny to detect disease susceptibility loci.
Bardel C, Danjean V, Hugot JP, Darlu P, Génin E. Bardel C, et al. BMC Genet. 2005 May 18;6:24. doi: 10.1186/1471-2156-6-24. BMC Genet. 2005. PMID: 15904492 Free PMC article. - Linkage disequilibrium and association studies in higher plants: present status and future prospects.
Gupta PK, Rustgi S, Kulwal PL. Gupta PK, et al. Plant Mol Biol. 2005 Mar;57(4):461-85. doi: 10.1007/s11103-005-0257-z. Plant Mol Biol. 2005. PMID: 15821975 Review. - Integration of association statistics over genomic regions using Bayesian adaptive regression splines.
Zhang X, Roeder K, Wallstrom G, Devlin B. Zhang X, et al. Hum Genomics. 2003 Nov;1(1):20-9. doi: 10.1186/1479-7364-1-1-20. Hum Genomics. 2003. PMID: 15601530 Free PMC article.
MeSH terms
LinkOut - more resources
Full Text Sources