Journal home
Advance online publication
Current issue
Archive
Press releases
Free Association (blog)
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Biotechnology
Nature Cell Biology
Nature Medicine
Nature Methods
Nature Reviews Cancer
Nature Reviews Genetics
Nature Reviews Molecular Cell Biology
news@nature.com
Nature Conferences
RNAi Gateway
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
Article
Nature Genetics  11, 402 - 408 (1995)
doi:10.1038/ng1295-402

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

Jeffrey R. O'Connell1 & Daniel E. Weeks1, 2

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

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

 Correspondence should be addressed to D.E.W.

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.

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 | PubMed  | ISI | ChemPort |
  2. Buetow, K.H. et al. Integrated human genome-wide maps constructed using the CEPH reference panel. Nature Genet. 6, 391−393 (1994). | Article | PubMed  | ISI | ChemPort |
  3. Murray, J.C. et al. A comprehensive human linkage map with centimorgan density. Cooperative Human Linkage Center (CHLC). Science 265, 2049−2054 (1994). | PubMed  | ISI | ChemPort |
  4. Gyapay, G. et al. The 1993−94 Généthon human genetic linkage map. Nature Genet. 7, 246−339 (1994). | Article | PubMed  | ISI | ChemPort |
  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 | PubMed  | ISI | ChemPort |
  6. Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794−801 (1992). | Article | PubMed  | ISI | ChemPort |
  7. Thompson, E.A. Information gain in joint linkage analysis. IMA J. Math. Appl. Med. Biol. 1, 31−49 (1984). | PubMed  | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | ChemPort |
  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).
  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). | PubMed  | ISI | ChemPort |
  12. Boehnke, M. Estimating the power of a proposed linkage study: a practical computer simulation approach. Am. J. hum. Genet. 39, 513−527 (1986). | PubMed  | ISI | ChemPort |
  13. Ott, J. Computer-simulation methods in human linkage analysis. Proc. natn. Acad. Sci. U.S.A. 86, 4175−4178 (1989). | ChemPort |
  14. Weeks, D.E., Ott, J. & Lathrop, G.M. SUNK: a general simulation program for linkage analysis. Am. J. hum. Genet. 47, A204 (1990).
  15. Demenais, F. & Lathrop, M. REGRESS: a computer program including the regressive approach into the LINKAGE programs. Genet. Epidemiol. 11, 291 (1994).
  16. Elston, R.C. & Stewart, J. A general model for the genetic analysis of pedigree data. Hum. Hered. 21, 523−542 (1971). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | ChemPort |
  21. Curtis, D. & Gurling, H. A procedure for combining two-point scores into a summary multipoint map. Hum. Hered. 43, 173−185 (1993). | PubMed  | ISI | ChemPort |
  22. Lange, K. & Sobel, E. A random walk method for computing genetic location scores. Am. J. hum. Genet. 49, 1320−1334 (1991). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  24. Thomas, D.C. & Cortessis, V. A Gibbs sampling approach to linkage analysis. Hum. Hered. 42, 63−76 (1992). | PubMed  | ISI | ChemPort |
  25. Kong, A., Cox, N., Frigge, M. & Irwin, M. Sequential imputation and multipoint linkage analysis. Genet Epidemiol. 10, 483−488 (1993). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  27. Irwin, M., Cox, N. & Kong, A. Sequential imputation for multilocus linkage analysis. Proc. natn. Acad. Sci. U.S.A. 91, 11684−11688 (1994). | ChemPort |
  28. Ott, J. Analysis of Human Genetic Linkage (Revised Edition) (Johns Hopkins University Press, Baltimore, 1991).
  29. Ott, J. A simple scheme for the analysis of HLA linkages in pedigrees. Ann. hum. Genet. 42, 255−257 (1978). | PubMed  | ISI | ChemPort |
  30. Braverman, M.S. An algorithm to improve the computational efficiency of genetic linkage analysis. Comput Biomed. Res. 18, 24−36 (1985). | Article | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI |
  32. Cottingham, R.W., Idury, R.M. & Schäffer, A.A. Faster sequential genetic linkage computations. Am. J. hum. Genet. 53, 252−263 (1993). | PubMed  | ISI |
  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). | PubMed  | ISI | ChemPort |
  34. Lathrop, G.M. & Lalouel, J.M. Efficient computations in multilocus linkage analysis. Am. J. hum. Genet. 42, 498−505 (1988). | PubMed  | ISI | ChemPort |
  35. Lange, K. & Goradia, T.M. An algorithm for automatic genotype elimination. Am. J. hum. Genet. 40, 250−256 (1987). | PubMed  | ISI | ChemPort |
  36. McNeill, D. & Freiberger, P. Fuzzy logic (Simon & Schuster, New York, 1993).
  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). | PubMed  | ChemPort |
  38. Levy-Lahad, E. et al. A familial Alzheimer's disease locus on chromosome 1. Science 269, 970−973 (1995). | PubMed  | ChemPort |
  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 | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  42. Nygaard, T.G. et al. Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. Nature Genet. 5, 386−391 (1993). | PubMed  | ISI | ChemPort |
  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 | PubMed  | ISI | ChemPort |
  44. Mamelka, P.M., Dyke, B. & MacCluer, J.W. Pedigree/Draw for the Apple Macintosh (Southwest Foundation for Biomedical Research, San Antonio, 1988).
  45. Lange, K. & Elston, R.C. Extensions to pedigree analysis I. Likelihood calculations for simple and complex pedigrees. Hum. Hered. 25, 95−105 (1975). | PubMed  | ISI | ChemPort |
  46. Ott, J. A computer program for linkage analysis of general human pedigrees. Am. J. hum. Genet. 28, 528−529 (1976). | PubMed  | ISI | ChemPort |
  47. Weeks, D.E., Lathrop, G.M. & Ott, J. Multipoint mapping under genetic interference. Hum. Hered. 43, 86−97 (1993). | PubMed  | ISI | ChemPort |
  48. Weeks, D.E., Ott, J. & Lathrop, G.M. Detection of genetic interference: simulation studies and mouse data. Genetics 136, 1217−1226 (1994). | PubMed  | ISI | ChemPort |
 Top
 Top
Abstract
Previous | Next
Table of contents
Download PDFDownload PDF
Send to a friendSend to a friend
Save this linkSave this link

Open Innovation Challenges

naturejobs

References
Export citation
Export references
natureproducts

Search buyers guide:

 
ADVERTISEMENT
 
Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | Permissions | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | naturereprints | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©1995 Nature Publishing Group | Privacy policy