Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set–recoding and fuzzy inheritance

Nature Genetics volume 11, pages 402–408 (1995)Cite this article

Abstract

As genetic marker maps have improved, multipoint linkage analysis has become a crucial part of all disease mapping studies. Paradoxically, multipoint lod scores become increasingly difficult to compute, particularly as the numbers of markers, marker alleles and untyped people increase. We have solved this problem by using a novel set–recoding scheme to recode each person's genotype and ‘fuzzy inheritance’ to infer transmission probabilities. Our approach is implemented in a memory–efficient computer program, VITESSE, for extremely rapid computation of exact multipoint likelihoods. VITESSE enables fast and precise multipoint mappin of disease loci with highly polymorphic markers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Weissenbach, J. A second generation linkage map of the human genome based on highly informative microsatellite loci. Gene 135, 275–278 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Buetow, K.H. et al. Integrated human genome-wide maps constructed using the CEPH reference panel. Nature Genet. 6, 391–393 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. Murray, J.C. et al. A comprehensive human linkage map with centimorgan density. Cooperative Human Linkage Center (CHLC). Science 265, 2049–2054 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Gyapay, G. et al. The 1993–94 Généthon human genetic linkage map. Nature Genet. 7, 246–339 (1994).

    Article  CAS  PubMed  Google Scholar 

  5. Matise, T.C., Pertin, M. & Chakravarti, A. Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genet. 6, 384–390 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Thompson, E.A. Information gain in joint linkage analysis. IMA J. Math. Appl. Med. Biol. 1, 31–49 (1984).

    Article  CAS  PubMed  Google Scholar 

  8. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am. J. hum. Genet. 37, 482–498 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

    Article  CAS  Google Scholar 

  10. Sobel, E., Lange, K., O'Connell, J.R. & Weeks, D.E. in Genetic mapping and DNA sequencing (eds Speed, T.P. & Waterman, M.S.) (Springer-Verlag, New York, 1995).

    Google Scholar 

  11. Weeks, D.E., Sobel, E., O'Connell, J.R. & Lange, K. Computer programs for multilocus haplotyping of general pedigrees. Am. J. hum. Genet. 56, 1506–1507 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Boehnke, M. Estimating the power of a proposed linkage study: a practical computer simulation approach. Am. J. hum. Genet. 39, 513–527 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ott, J. Computer-simulation methods in human linkage analysis. Proc. natn. Acad. Sci. U.S.A. 86, 4175–4178 (1989).

    Article  CAS  Google Scholar 

  14. Weeks, D.E., Ott, J. & Lathrop, G.M. SUNK: a general simulation program for linkage analysis. Am. J. hum. Genet. 47, A204 (1990).

    Google Scholar 

  15. Demenais, F. & Lathrop, M. REGRESS: a computer program including the regressive approach into the LINKAGE programs. Genet. Epidemiol. 11, 291 (1994).

    Google Scholar 

  16. Elston, R.C. & Stewart, J. A general model for the genetic analysis of pedigree data. Hum. Hered. 21, 523–542 (1971).

    Article  CAS  PubMed  Google Scholar 

  17. Lathrop, G.M., Lalouel, J.M. & White, R.L. Construction of human linkage maps: likelihood calculations for muttitocus analysis. Genet Epidemiol. 3, 39–52 (1986).

    Article  CAS  PubMed  Google Scholar 

  18. Kruglyak, L., Daly, M.J. & Lander, E.S. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am. J. hum. Genet. 56, 519–527 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Rothschild, C.B. et al. A genetic map of chromosome 20q12–q13.1: Multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the young (MODY) locus. Am. J. hum. Genet. 52, 110–123 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lander, E.S. & Green, P. Construction of multilocus genetic linkage maps in humans. Proc. natn. Acad. Sci. U.S.A. 84, 2363–2367 (1987).

    Article  CAS  Google Scholar 

  21. Curtis, D. & Gurling, H. A procedure for combining two-point scores into a summary multipoint map. Hum. Hered. 43, 173–185 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Lange, K. & Sobel, E. A random walk method for computing genetic location scores. Am. J. hum. Genet. 49, 1320–1334 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Foroud, T. et al. Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: Linkage analysis of 111 families by an international consortium. Am. J. hum. Genet. 49, 1263–1279 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Thomas, D.C. & Cortessis, V. A Gibbs sampling approach to linkage analysis. Hum. Hered. 42, 63–76 (1992).

    Article  CAS  PubMed  Google Scholar 

  25. Kong, A., Cox, N., Frigge, M. & Irwin, M. Sequential imputation and multipoint linkage analysis. Genet Epidemiol. 10, 483–488 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. Guo, S.W. & Thompson, E.A. A Monte Carlo method for combined segregation and linkage analysis. Am. J. hum. Genet. 51, 1111–1126 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Irwin, M., Cox, N. & Kong, A. Sequential imputation for multilocus linkage analysis. Proc. natn. Acad. Sci. U.S.A. 91, 11684–11688 (1994).

    Article  CAS  Google Scholar 

  28. Ott, J. Analysis of Human Genetic Linkage (Revised Edition) (Johns Hopkins University Press, Baltimore, 1991).

    Google Scholar 

  29. Ott, J. A simple scheme for the analysis of HLA linkages in pedigrees. Ann. hum. Genet. 42, 255–257 (1978).

    Article  CAS  PubMed  Google Scholar 

  30. Braverman, M.S. An algorithm to improve the computational efficiency of genetic linkage analysis. Comput Biomed. Res. 18, 24–36 (1985).

    Article  CAS  PubMed  Google Scholar 

  31. Lange, K. & Weeks, D.E. Efficient computation of lod scores: genotype elimination, genotype redefinition, and hybrid maximum likelihood algorithms. Ann. hum. Genet. 53, 67–83 (1989).

    Article  CAS  PubMed  Google Scholar 

  32. Cottingham, R.W., Idury, R.M. & Schäffer, A.A. Faster sequential genetic linkage computations. Am. J. hum. Genet. 53, 252–263 (1993).

    PubMed  PubMed Central  Google Scholar 

  33. Lathrop, G.M. & Lalouel, J.-M. Easy calculations of lod scores and genetic risks on small computers. Am. J. hum. Genet. 36, 460–465 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Lathrop, G.M. & Lalouel, J.M. Efficient computations in multilocus linkage analysis. Am. J. hum. Genet. 42, 498–505 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Lange, K. & Goradia, T.M. An algorithm for automatic genotype elimination. Am. J. hum. Genet. 40, 250–256 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. McNeill, D. & Freiberger, P. Fuzzy logic (Simon & Schuster, New York, 1993).

    Google Scholar 

  37. Pericak-Vance, M.A. et al. Linkage analysis in familial Alzheimer disease: description of the Duke and Boston data sets. Genet. Epidemiol. 10, 361–364 (1993).

    Article  CAS  PubMed  Google Scholar 

  38. Levy-Lahad, E. et al. A familial Alzheimer's disease locus on chromosome 1. Science 269, 970–973 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Kass, S. et al. A gene defect that causes conduction system disease and dilated cardiomyopathy maps to chromosome 1p1–1q1. Nature Genet. 7, 546–551 (1994).

    Article  CAS  PubMed  Google Scholar 

  40. Worthington, J. et al. The Arthritis and Rheumatism Council's National Repository of Family Material: pedigrees from the first 100 rheumatoid arthritis families containing affected sibling pairs. Br. J. Rheumatol. 33, 970–976 (1994).

    Article  CAS  PubMed  Google Scholar 

  41. Bamshad, M. et al. A gene for distal arthrogryposis type I maps to the pericentromeric region of chromosome 9. Am. J. hum. Genet. 55, 1153–1158 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Nygaard, T.G. et al. Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. Nature Genet. 5, 386–391 (1993).

    Article  CAS  PubMed  Google Scholar 

  43. Ichinose, H. et al. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nature Genet. 8, 236–242 (1994).

    Article  CAS  PubMed  Google Scholar 

  44. Mamelka, P.M., Dyke, B. & MacCluer, J.W. Pedigree/Draw for the Apple Macintosh (Southwest Foundation for Biomedical Research, San Antonio, 1988).

    Google Scholar 

  45. Lange, K. & Elston, R.C. Extensions to pedigree analysis I. Likelihood calculations for simple and complex pedigrees. Hum. Hered. 25, 95–105 (1975).

    Article  CAS  PubMed  Google Scholar 

  46. Ott, J. A computer program for linkage analysis of general human pedigrees. Am. J. hum. Genet. 28, 528–529 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Weeks, D.E., Lathrop, G.M. & Ott, J. Multipoint mapping under genetic interference. Hum. Hered. 43, 86–97 (1993).

    Article  CAS  PubMed  Google Scholar 

  48. Weeks, D.E., Ott, J. & Lathrop, G.M. Detection of genetic interference: simulation studies and mouse data. Genetics 136, 1217–1226 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA

    Jeffrey R. O'Connell & Daniel E. Weeks

  2. The Wellcome Trust Centre for Human Genetics, University of Oxford, Windmill Road, Oxford, OX3 7BN, UK

    Daniel E. Weeks

Authors
  1. Jeffrey R. O'Connell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel E. Weeks
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'Connell, J., Weeks, D. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set–recoding and fuzzy inheritance. Nat Genet 11, 402–408 (1995). https://doi.org/10.1038/ng1295-402

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1295-402

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing