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. 1999 Feb;151(2):803–820. doi: 10.1093/genetics/151.2.803

A second-generation genetic linkage map of the domestic dog, Canis familiaris.

M W Neff 1, K W Broman 1, C S Mellersh 1, K Ray 1, G M Acland 1, G D Aguirre 1, J S Ziegle 1, E A Ostrander 1, J Rine 1
PMCID: PMC1460484  PMID: 9927471

Abstract

Purebred strains, pronounced phenotypic variation, and a high incidence of heritable disease make the domestic dog uniquely suited to complement genetic analyses in humans and mice. A comprehensive genetic linkage map would afford many opportunities in dogs, ranging from the positional cloning of disease genes to the dissection of quantitative differences in size, shape, and behavior. Here we report a canine linkage map with the number of mapped loci expanded to 276 and 10-cM coverage extended to 75-90% of the genome. Most of the 38 canine autosomes are likely represented in the collection of 39 autosomal linkage groups. Eight markers were sufficiently informative to detect linkage at distances of 10-13 cM, yet remained unlinked to any other marker. Taken together, the results suggested a genome size of about 27 M. As in other species, the genetic length varied between sexes, with the female autosomal distance being approximately 1.4-fold greater than that of male meioses. Fifteen markers anchored well-described genes on the map, thereby serving as landmarks for comparative mapping in dogs. We discuss the utility of the current map and outline steps necessary for future map improvement.

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Selected References

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  1. Acland G. M., Ray K., Mellersh C. S., Gu W., Langston A. A., Rine J., Ostrander E. A., Aguirre G. D. Linkage analysis and comparative mapping of canine progressive rod-cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3048–3053. doi: 10.1073/pnas.95.6.3048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bihoreau M. T., Gauguier D., Kato N., Hyne G., Lindpaintner K., Rapp J. P., James M. R., Lathrop G. M. A linkage map of the rat genome derived from three F2 crosses. Genome Res. 1997 May;7(5):434–440. doi: 10.1101/gr.7.5.434. [DOI] [PubMed] [Google Scholar]
  4. Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
  5. Broman K. W., Murray J. C., Sheffield V. C., White R. L., Weber J. L. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet. 1998 Sep;63(3):861–869. doi: 10.1086/302011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Chakravarti A., Lasher L. K., Reefer J. E. A maximum likelihood method for estimating genome length using genetic linkage data. Genetics. 1991 May;128(1):175–182. doi: 10.1093/genetics/128.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deschênes S. M., Puck J. M., Dutra A. S., Somberg R. L., Felsburg P. J., Henthorn P. S. Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency. Genomics. 1994 Sep 1;23(1):62–68. doi: 10.1006/geno.1994.1459. [DOI] [PubMed] [Google Scholar]
  9. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  10. Dietrich W. F., Miller J., Steen R., Merchant M. A., Damron-Boles D., Husain Z., Dredge R., Daly M. J., Ingalls K. A., O'Connor T. J. A comprehensive genetic map of the mouse genome. Nature. 1996 Mar 14;380(6570):149–152. doi: 10.1038/380149a0. [DOI] [PubMed] [Google Scholar]
  11. Francisco L. V., Langston A. A., Mellersh C. S., Neal C. L., Ostrander E. A. A class of highly polymorphic tetranucleotide repeats for canine genetic mapping. Mamm Genome. 1996 May;7(5):359–362. doi: 10.1007/s003359900104. [DOI] [PubMed] [Google Scholar]
  12. Francisco L. V., Langston A. A., Mellersh C. S., Neal C. L., Ostrander E. A. A class of highly polymorphic tetranucleotide repeats for canine genetic mapping. Mamm Genome. 1996 May;7(5):359–362. doi: 10.1007/s003359900104. [DOI] [PubMed] [Google Scholar]
  13. Fredholm M., Winterø A. K. Variation of short tandem repeats within and between species belonging to the Canidae family. Mamm Genome. 1995 Jan;6(1):11–18. doi: 10.1007/BF00350887. [DOI] [PubMed] [Google Scholar]
  14. Gyapay G., Schmitt K., Fizames C., Jones H., Vega-Czarny N., Spillett D., Muselet D., Prud'homme J. F., Dib C., Auffray C. A radiation hybrid map of the human genome. Hum Mol Genet. 1996 Mar;5(3):339–346. doi: 10.1093/hmg/5.3.339. [DOI] [PubMed] [Google Scholar]
  15. Holmes N. G., Dickens H. F., Parker H. L., Binns M. M., Mellersh C. S., Sampson J. Eighteen canine microsatellites. Anim Genet. 1995 Apr;26(2):132–133. doi: 10.1111/j.1365-2052.1995.tb02659.x. [DOI] [PubMed] [Google Scholar]
  16. Holmes N. G., Mellersh C. S., Humphreys S. J., Binns M. M., Holliman A., Curtis R., Sampson J. Isolation and characterization of microsatellites from the canine genome. Anim Genet. 1993 Aug;24(4):289–292. doi: 10.1111/j.1365-2052.1993.tb00313.x. [DOI] [PubMed] [Google Scholar]
  17. Holmes N. G., Strange N. J., Binns M. M., Mellersh C. S., Sampson J. Three polymorphic canine microsatellites. Anim Genet. 1994 Jun;25(3):200–200. doi: 10.1111/j.1365-2052.1994.tb00122.x. [DOI] [PubMed] [Google Scholar]
  18. Hung T., Mak K., Fong K. A specificity enhancer for polymerase chain reaction. Nucleic Acids Res. 1990 Aug 25;18(16):4953–4953. doi: 10.1093/nar/18.16.4953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kappes S. M., Keele J. W., Stone R. T., McGraw R. A., Sonstegard T. S., Smith T. P., Lopez-Corrales N. L., Beattie C. W. A second-generation linkage map of the bovine genome. Genome Res. 1997 Mar;7(3):235–249. doi: 10.1101/gr.7.3.235. [DOI] [PubMed] [Google Scholar]
  20. Lincoln S. E., Lander E. S. Systematic detection of errors in genetic linkage data. Genomics. 1992 Nov;14(3):604–610. doi: 10.1016/s0888-7543(05)80158-2. [DOI] [PubMed] [Google Scholar]
  21. Lingaas F., Sorensen A., Juneja R. K., Johansson S., Fredholm M., Wintero A. K., Sampson J., Mellersh C., Curzon A., Holmes N. G. Towards construction of a canine linkage map: establishment of 16 linkage groups. Mamm Genome. 1997 Mar;8(3):218–221. doi: 10.1007/s003359900393. [DOI] [PubMed] [Google Scholar]
  22. Marklund L., Johansson Moller M., Høyheim B., Davies W., Fredholm M., Juneja R. K., Mariani P., Coppieters W., Ellegren H., Andersson L. A comprehensive linkage map of the pig based on a wild pig-Large White intercross. Anim Genet. 1996 Aug;27(4):255–269. doi: 10.1111/j.1365-2052.1996.tb00487.x. [DOI] [PubMed] [Google Scholar]
  23. Mellersh C. S., Langston A. A., Acland G. M., Fleming M. A., Ray K., Wiegand N. A., Francisco L. V., Gibbs M., Aguirre G. D., Ostrander E. A. A linkage map of the canine genome. Genomics. 1997 Dec 15;46(3):326–336. doi: 10.1006/geno.1997.5098. [DOI] [PubMed] [Google Scholar]
  24. Nadeau J. H., Grant P. L., Mankala S., Reiner A. H., Richardson J. E., Eppig J. T. A Rosetta stone of mammalian genetics. Nature. 1995 Jan 26;373(6512):363–365. doi: 10.1038/373363a0. [DOI] [PubMed] [Google Scholar]
  25. Ostrander E. A., Sprague G. F., Jr, Rine J. Identification and characterization of dinucleotide repeat (CA)n markers for genetic mapping in dog. Genomics. 1993 Apr;16(1):207–213. doi: 10.1006/geno.1993.1160. [DOI] [PubMed] [Google Scholar]
  26. Robic A., Milan D., Woloszyn N., Riquet J., Yerle M., Nagel M., Bonnet M., Pinton P., Dalens M., Gellin J. Contribution to the physically anchored linkage map of the pig. Anim Genet. 1997 Apr;28(2):94–102. doi: 10.1111/j.1365-2052.1997.00084.x. [DOI] [PubMed] [Google Scholar]
  27. Selden J. R., Moorhead P. S., Oehlert M. L., Patterson D. F. The Giemsa banding pattern of the canine karyotype. Cytogenet Cell Genet. 1975;15(6):380–387. doi: 10.1159/000130537. [DOI] [PubMed] [Google Scholar]
  28. Shibuya H., Collins B. K., Huang T. H., Johnson G. S. A polymorphic (AGGAAT)n tandem repeat in an intron of the canine von Willebrand factor gene. Anim Genet. 1994 Apr;25(2):122–122. doi: 10.1111/j.1365-2052.1994.tb00094.x. [DOI] [PubMed] [Google Scholar]
  29. Shuber A. P., Grondin V. J., Klinger K. W. A simplified procedure for developing multiplex PCRs. Genome Res. 1995 Dec;5(5):488–493. doi: 10.1101/gr.5.5.488. [DOI] [PubMed] [Google Scholar]
  30. Slonim D., Kruglyak L., Stein L., Lander E. Building human genome maps with radiation hybrids. J Comput Biol. 1997 Winter;4(4):487–504. doi: 10.1089/cmb.1997.4.487. [DOI] [PubMed] [Google Scholar]
  31. Stanford J. L., Just J. J., Gibbs M., Wicklund K. G., Neal C. L., Blumenstein B. A., Ostrander E. A. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res. 1997 Mar 15;57(6):1194–1198. [PubMed] [Google Scholar]
  32. Stewart E. A., McKusick K. B., Aggarwal A., Bajorek E., Brady S., Chu A., Fang N., Hadley D., Harris M., Hussain S. An STS-based radiation hybrid map of the human genome. Genome Res. 1997 May;7(5):422–433. doi: 10.1101/gr.7.5.422. [DOI] [PubMed] [Google Scholar]
  33. Switoński M., Reimann N., Bosma A. A., Long S., Bartnitzke S., Pieńkowska A., Moreno-Milan M. M., Fischer P. Report on the progress of standardization of the G-banded canine (Canis familiaris) karyotype. Committee for the Standardized Karyotype of the Dog (Canis familiaris). Chromosome Res. 1996 Jun;4(4):306–309. doi: 10.1007/BF02263682. [DOI] [PubMed] [Google Scholar]
  34. Thomas R., Holmes N. G., Fischer P. E., Dickens H. F., Breen M., Sampson J., Binns M. M. Eight canine microsatellites. Anim Genet. 1997 Apr;28(2):153–154. [PubMed] [Google Scholar]
  35. Wang D. G., Fan J. B., Siao C. J., Berno A., Young P., Sapolsky R., Ghandour G., Perkins N., Winchester E., Spencer J. Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science. 1998 May 15;280(5366):1077–1082. doi: 10.1126/science.280.5366.1077. [DOI] [PubMed] [Google Scholar]
  36. Werner P., Raducha M. G., Prociuk U., Henthorn P. S., Patterson D. F. Physical and linkage mapping of human chromosome 17 loci to dog chromosomes 9 and 5. Genomics. 1997 May 15;42(1):74–82. doi: 10.1006/geno.1997.4723. [DOI] [PubMed] [Google Scholar]
  37. Yuzbasiyan-Gurkan V., Blanton S. H., Cao Y., Ferguson P., Li J., Venta P. J., Brewer G. J. Linkage of a microsatellite marker to the canine copper toxicosis locus in Bedlington terriers. Am J Vet Res. 1997 Jan;58(1):23–27. [PubMed] [Google Scholar]
  38. de Gortari M. J., Freking B. A., Cuthbertson R. P., Kappes S. M., Keele J. W., Stone R. T., Leymaster K. A., Dodds K. G., Crawford A. M., Beattie C. W. A second-generation linkage map of the sheep genome. Mamm Genome. 1998 Mar;9(3):204–209. doi: 10.1007/s003359900726. [DOI] [PubMed] [Google Scholar]

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