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The use of a genetic map of biallelic markers in linkage studies

Nature Genetics volume 17, pages 21–24 (1997)Cite this article

Abstract

Improvements in genetic mapping techniques have driven recent progress in human genetics. The use of single nucleotide polymorphisms (SNPs) as biallelic genetic markers offers the promise of rapid, highly automated genotyping. As maps of SNPs and the techniques for genotyping them are being developed, it is important to consider what properties such maps must have in order for them to be useful for linkage studies. I examine how polymorphic and densely spaced biallelic markers need to be for extraction of most of the inheritance information from human pedigrees, and compare maps of biallelics with today's genome-scanning sets of microsatellite markers. I conclude that a map of 700–900 moderately polymorphic biallelic markers is equivalent—and a map of 1,500–3,000 superior—to the current 300–400 microsatellite marker sets.

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References

  1. Botstein, D., White, D.L., Skolnick, M. & Davis, R.W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32, 314–331 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Wyman, A.R. & White, R.W. A highly polymorphic locus in human DNA. Proc. Natl. Acad. Sci. USA 77, 6754–6758 (1980).

    CAS  Article  Google Scholar 

  3. Gusella, J.F. et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306, 234–238 (1983).

    CAS  Article  Google Scholar 

  4. Donis-Keller, H. et al. A genetic linkage map of the human genome. Cell 51, 319–337 (1987).

    CAS  Article  Google Scholar 

  5. Weber, J.L. & May, P.E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. Hum. Genet. 44, 388–396 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Cooperative Human Linkage Center. A comprehensive human linkage map with centimorgan density. Science 265, 2049–2054 (1994).

    CAS  Article  Google Scholar 

  7. Dib, C. et al. A comprehensive genetic map of the human genome based on 5264 microsatellites. Nature 380, 152–154 (1996).

    CAS  Article  Google Scholar 

  8. Hofker, M.H. et al. The X chromosome shows less genetic variation at restriction sites than the autosomes. Am. J. Hum. Genet. 39, 438–451 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Cooper, D.N., Smith, B.A., Cooke, H.J., Niemann, S. & Schmidtke, J. An estimate of unique DNA sequence heterozygosity in the human genome. Hum. Genet. 69, 201–205 (1985).

    CAS  Article  Google Scholar 

  10. Nickerson, D.A. et al. Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay. Proc. Natl. Acad. Sci. USA 87, 8923–8927 (1990).

    CAS  Article  Google Scholar 

  11. Livak, K.J., Marmaro, J. & Todd, J.A. Towards fully automated genome-wide polymorphism screening. Nature Genet. 9, 341–342 (1995).

    CAS  Article  Google Scholar 

  12. Saiki, R.K., Walsh, P.S., Levenson, C.H. & Erlich, H.A. Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc. Natl. Acad. Sci. USA 86, 6230–6234 (1989).

    CAS  Article  Google Scholar 

  13. Syyanen, A.-C., Aalto-Setala, K., Harju, L., Kontula, K. & Soderlund, H. A primer-guided nucleotide incorporation assay in the genotyping of apolipoprotein E. Genomics 8, 684–692 (1990).

    Article  Google Scholar 

  14. Wu, D.Y., Ugozzoli, L., Pal, B.K. & Wallace, R.B. Allele-specific enzymatic amplification of β-globin genomic DNA for diagnosis of sickle cell anemia. Proc Natl. Acad. Sci. USA 86, 2757–2760 (1989).

    CAS  Article  Google Scholar 

  15. Wang, D. et al. Toward a third generation genetic map of the human genome based on biallelic polymorphisms. Am. J. Hum. Genet. 59, A3 (1996).

    Google Scholar 

  16. Chee, M. et al. Accessing genetic information with high-density DNA arrays. Science 274, 610–614 (1996).

    CAS  Article  Google Scholar 

  17. Kruglyak, L. & Lander, E.S. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am. J. Hum. Genet. 57, 439–454 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Reed, P.W. et al. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nature Genet. 7, 390–395 (1994).

    CAS  Article  Google Scholar 

  20. Dubovsky, J., Sheffield, V.C., Duyk, G.M. & Weber, J.L. Sets of short tandem repeat polymorphisms for efficient linkage screening of the human genome. Hum. Mol. Genet. 4, 449–452 (1995).

    CAS  Article  Google Scholar 

  21. Elston, R.C. Designs for the global search of the human genome by linkage analysis. in Proceedings of the 16th International Biometrics Conference 39–51 (Hamilton, New Zealand, 1992).

    Google Scholar 

  22. Brown, D.L., Gorin, M.B. & Weeks, D.E. Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis. Am. J. Hum. Genet. 54, 544–552 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Terwilliger, J.D., Ding, Y. & Ott, J. On the relative importance of marker heterozygosity and intermarker distance in gene mapping. Genomics 13, 951–956 (1992).

    CAS  Article  Google Scholar 

  24. Lander, E.S. & Botstein, D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236, 1567–1570 (1987).

    CAS  Article  Google Scholar 

  25. O'Connell, J.R. & Weeks, D.E. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nature Genet. 11, 402–408 (1995).

    CAS  Article  Google Scholar 

  26. Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996).

    CAS  Article  Google Scholar 

  27. Lander, E.S. The new genomics: global views of biology. Science 274, 536–539 (1996).

    CAS  Article  Google Scholar 

  28. Collins, F.S. Positional cloning moves from perditional to traditional. Nature Genet. 9, 347–350 (1995).

    CAS  Article  Google Scholar 

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  1. Whitehead Institute for Biomedical Research, 1 Kendall Square, Bldg. 300, Cambridge, Massachusetts, 02139, USA

    Leonid Kruglyak

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Kruglyak, L. The use of a genetic map of biallelic markers in linkage studies. Nat Genet 17, 21–24 (1997). https://doi.org/10.1038/ng0997-21

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