Abstract
A canine integrated linkage-radiation map has been recently constructed by using microsatellite markers. This map, with a good coverage of the canine genome, allows for a genome-wide search for the extent and distribution of linkage disequilibrium derived from linkage and evolutionary forces. In this study, we genotyped an outbred pedigree between Labrador retriever and Greyhound breeds with a set of microsatellite markers (240) from the canine linkage map. Linkage disequilibrium was measured between all syntenic and nonsyntenic marker pairs. Analysis of syntenic pairs revealed a significant correlation (−0.229, P < 0.001) between linkage disequilibrium and genetic distance (log transformed). Significant linkage disequilibria were observed more frequently between syntenic pairs spaced <40 cM than those paced >40 cM. There is a clear trend for linkage disequilibrium to decline with marker distance. From our results, a genome-wide screen with markers at low to moderate density (1–2 per 10 cM) should take full advantage of linkage disequilibrium for quantitative trait locus map** in dogs. This study supports the appropriateness of linkage disequilibrium analysis to detect and map quantitative trait loci underlying complex traits in dogs.
Similar content being viewed by others
References
KG Ardlie L Kruglyak M Seielstad (2002) ArticleTitlePatterns of linkage disequilibrium in the human genome. Nat Rev Genet 3 299–309 Occurrence Handle10.1038/nrg777 Occurrence Handle1:CAS:528:DC%2BD38XjtFOrt7w%3D Occurrence Handle11967554
S Bliss RJ Todhunter R Quaas G Casella RL Wu et al. (2002) ArticleTitleQuantitative genetics of traits associated with hip dysplasia in a canine pedigree constructed by mating dysplastic Labrador Retrievers with unaffected Greyhounds. Am J Vet Res 63 1029–1035 Occurrence Handle12118665
M Boehnke (2000) ArticleTitleA look at linkage disequilibrium. Nat Genet 25 246–247 Occurrence Handle10.1038/76980 Occurrence Handle1:CAS:528:DC%2BD3cXkvFKlsb8%3D Occurrence Handle10888861
M Breen S Jouquand C Renier CS Mellersh et al. (2001) ArticleTitleChromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes. Mamm Genome 11 1784–1795 Occurrence Handle10.1101/gr.189401 Occurrence Handle1:CAS:528:DC%2BD3MXnvFCmtbg%3D
NH Chapman EM Wijsman (1998) ArticleTitleGenome screens using linkage disequilibrium tests: optimal marker characteristics and feasibility. Am J Hum Genet 63 1872–1885 Occurrence Handle10.1086/302139 Occurrence Handle1:CAS:528:DyaK1MXlt1Sitw%3D%3D Occurrence Handle9837839
A Cox NJ Camp MJH Nicklin FS di Giovine GW Duff (1998) ArticleTitleAn analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a novel grou** method for multiallelic markers. Am J Hum Genet 62 1180–1188 Occurrence Handle1:CAS:528:DyaK1cXlslCitb0%3D Occurrence Handle9545388
E Dawson GR Abecasis S Bumpstead Y Chen S Hunt et al. (2002) ArticleTitleA first-generation linkage disequilibrium map of human chromosome 22. Nature 418 544–548 Occurrence Handle1:CAS:528:DC%2BD38Xls12nuro%3D Occurrence Handle12110843
AM Dunning F Durocher CS Healey MD Teare SE McBride et al. (2000) ArticleTitleThe extent of linkage disequilibrium in four populations with distinct demographic histories. Am J Hum Genet 67 1544–1554 Occurrence Handle1:CAS:528:DC%2BD3cXovVKisr8%3D Occurrence Handle11078480
F Farnir W Coppieters JJ Arranz P Berzi N Cambisano et al. (2000) ArticleTitleExtensive genome-wide linkage disequilibrium in cattle. Genome Res 10 220–227 Occurrence Handle10.1101/gr.10.2.220 Occurrence Handle1:CAS:528:DC%2BD3cXhsVOks70%3D
F Farnir B Grisart W Coppieters J Riquet P Berzi et al. (2002) ArticleTitleSimultaneous mining of linkage and linkage disequilibrium to fine map quantitative trait loci in outbred half-sib pedigrees: revisiting the location of a quantitative trait locus with major effect on milk production on bovine chromosome 14. Genetics 161 275–287 Occurrence Handle1:CAS:528:DC%2BD38XkslChtb8%3D Occurrence Handle12019241
C Haley (1999) Advances in quantitative trait locus map**. JCM Dekkers SJ Lamont MF Rothschild (Eds) From JL Lush to Genomics: Visions for Animal Breeding and Genetics. Iowa State University Press Ames, Iowa 47–59
D Hall EM Wijsman JL Roos JA Gogos M Karayiorgou (2002) ArticleTitleExtended intermarker linkage disequilibrium in the afrikaners. Genome Res 12 956–961 Occurrence Handle10.1101/gr.136202 Occurrence Handle1:CAS:528:DC%2BD38Xks12hs74%3D Occurrence Handle12045148
P Hedrick (1987) ArticleTitleGametic disequilibrium measures: proceed with caution. Genetics 117 331–341 Occurrence Handle1:STN:280:BieD3s%2FmsFI%3D Occurrence Handle3666445
L Kruglyak (1999) ArticleTitleProspects for whole-genome linkage disequilibrium map** of common disease genes. Nat Genet 22 139–144 Occurrence Handle10.1038/9642 Occurrence Handle10369254
RC Lewontin (1964) ArticleTitleThe interaction of selection and linkage. I. General considerations; heterotic models. Genetics 49 49–67
RC Lewontin (1988) ArticleTitleOn measures of gametic disequilibrium. Genetics 120 849–852 Occurrence Handle1:STN:280:BiaC3sjptFA%3D Occurrence Handle3224810
AF McRae JC McEwan KG Dodds T Wilson AM Crawford et al. (2002) ArticleTitleLinkage disequilibrium in domestic sheep. Genetics 160 1131–1122
CS Mellersh AA Langston GM Acland MA Fleming K Ray et al. (1997) ArticleTitleA linkage map of the canine genome. Genomics 46 326–336 Occurrence Handle10.1006/geno.1997.5098 Occurrence Handle1:CAS:528:DyaK1cXmt12jtw%3D%3D Occurrence Handle9441735
CS Mellersh C Hitte M Richman F Vignaux C Priat et al. (2002) ArticleTitleAn integrated linkage-radiation hybrid map of the canine genome. Mamm Genome 11 120–130 Occurrence Handle10.1007/s003350010024
THE Meuwissen A Karlsen S Lien I Olsaker ME Goddard (2002) ArticleTitleFine map** of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium map**. Genetics 161 373–379 Occurrence Handle1:CAS:528:DC%2BD38XkslChu74%3D Occurrence Handle12019251
EA Ostrander L Kruglyak (2000) ArticleTitleUnleashing the canine genome. Genome Res 10 1271–1274 Occurrence Handle10.1101/gr.155900 Occurrence Handle1:CAS:528:DC%2BD3cXms1yjt7c%3D Occurrence Handle10984444
EG Puffenberger K Hosoda SS Washington (1994) ArticleTitleA missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell 79 1257–1266 Occurrence Handle1:CAS:528:DyaK2M**vVajsr0%3D Occurrence Handle8001158
DE Reich M Cargill S Bolk J Ireland PC Sabeti et al. (2001) ArticleTitleLinkage disequilibrium in the human genome. Nature 411 199–204 Occurrence Handle10.1038/35075590 Occurrence Handle11346797
M Richman CS Mellersh C Andre F Gailbert EA Ostrander (2001) ArticleTitleCharacterization of a minimal screening set of 172 microsatellite markers for genome-wide screens of the canine genome. J Biochem Biophys Methods 47 137–149 Occurrence Handle10.1016/S0165-022X(00)00160-3 Occurrence Handle1:CAS:528:DC%2BD3MXhtFeitb0%3D Occurrence Handle11179770
P Savolainen Y-P Zhang J Luo J Lundeberg T Leitner (2002) ArticleTitleGenetic evidence for an East Asian origin of domestic dogs. Science 298 1610–1613 Occurrence Handle10.1126/science.1073906 Occurrence Handle1:CAS:528:DC%2BD38Xosl2ktbg%3D Occurrence Handle12446907
P Taillon-Miller I Bauer-Sardina NL Saccone J Putzel T Laitinen et al. (2000) ArticleTitleJuxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nat Genet 25 324–328 Occurrence Handle1:CAS:528:DC%2BD3cXkvFKksbk%3D Occurrence Handle10888883
RJ Todhunter GM Acland M Olivier AJ Williams M Vernier-Singer et al. (1999) ArticleTitleAn outcrossed canine pedigree for linkage analysis of hip dysplasia. J Hered 90 83–92 Occurrence Handle10.1093/jhered/90.1.83 Occurrence Handle1:STN:280:DyaK1M7kt1equg%3D%3D Occurrence Handle9987910
RJ Todhunter G Casella SP Bliss G Lust AJ William et al. (2003a) ArticleTitlePower of a dysplastic Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia. Am J Vet Res 64 418–424
RJ Todhunter SR Bliss SR Quaas G Lust G Casella et al. (2003b) ArticleTitleGenetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree. J Hered 94 39–48 Occurrence Handle1:CAS:528:DC%2BD3sXktVWhu7w%3D
BS Weir (1996) Genetic Data Analysis II. Sinauer Associates Sunderland Mass.
KM Weiss AG Clark (2002) ArticleTitleLinkage disequilibrium and the map** of complex human traits. Trends Genet 18 19–24 Occurrence Handle10.1016/S0168-9525(01)02550-1 Occurrence Handle1:CAS:528:DC%2BD3MXpt1agsr8%3D Occurrence Handle11750696
JF Wilson DB Goldstein (2000) ArticleTitleConsistent long-range linkage disequilibrium generated by admixture in a Bantu-Semitic hybrid population. Am J Hum Genet 67 926–935 Occurrence Handle10.1086/303083 Occurrence Handle1:CAS:528:DC%2BD3cXnsVCgsL8%3D Occurrence Handle10961910
RL Wu Z-B Zeng (2001) ArticleTitleJoint linkage and linkage disequilibrium map** in natural populations. Genetics 157 899–909 Occurrence Handle1:STN:280:DC%2BD3M3osFWhuw%3D%3D Occurrence Handle11157006
RL Wu C-X Ma G Casella (2002) ArticleTitleJoint linkage and linkage disequilibrium map** of quantitative trait loci in natural populations. Genetics 160 779–792 Occurrence Handle1:CAS:528:DC%2BD38**tlWrsLc%3D Occurrence Handle11861578
R-C Yang (2000) ArticleTitleZygotic associations and multilocus statistics in a nonequilibrium diploid population. Genetics 155 1449–1458 Occurrence Handle1:STN:280:DC%2BD3cvgsVSmsw%3D%3D Occurrence Handle10880502
R-C Yang (2002) ArticleTitleAnalysis of multilocus zygotic associations. Genetics 161 435–445 Occurrence Handle1:CAS:528:DC%2BD38XkslChu7c%3D Occurrence Handle12019256
Acknowledgements
We thank two anonymous referees for constructive comments on this manuscript, which led to a better presentation. This work was supported by a grant from the Morris Animal Foundation, NIH grant AR36554, the Consolidated Research Grant Program, the Cornell Advanced Technology, Biotechnology Program, Nestle Purina Inc., NALBI Mammalian Genoty** Service, Marshfield Medical Research Foundation, Marshfield, WI, Cornell University College of Veterinary Medicine Unrestricted Alumni Funds, and an Outstanding Young Investigators Award (No. 30128017) of the National Natural Science Foundation of China to R. Wu. We thank Margaret Vernier-Singer, Alm Jo Williams, and Liz Grisanzio for expert technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lou, XY., Todhunter, R.J., Lin, M. et al. The extent and distribution of linkage disequilibrium in a multi-hierarchic outbred canine pedigree . Mamm Genome 14, 555–564 (2003). https://doi.org/10.1007/s00335-003-2272-1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00335-003-2272-1