Nature Genetics
6, 384 - 390 (1994)
doi:10.1038/ng0494-384
Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage mapTara Cox Matise1, Mark Perlin3
& Aravinda Chakravarti1, 2, 4
1Department of Human Genetics, University of Pittsburgh, 130 De Soto St. Pittsburgh, Pennsylvania, 15261, USA
2Department of Psychiatry,University of Pittsburgh, 130 De Soto St. Pittsburgh, Pennsylvania, 15261, USA
3School of Computer Science, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, USA
4A.C. present address: Department of Genetics, BRB 721, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA Correspondence should be addressed to A.C. High−resolution genetic linkage maps are indispensable for positional cloning of disease genes Current procedures for map construction, although aided considerably by many existing computer programs, require extensive user−intervention at each of many repetitive steps This is time consuming, labour intensive and increases the chance of error. We have developed an expert system computer program, MultiMap, which automates this step−by−step procedure. MultiMap is based on a novel map construction algorithm and allows investigator control of marker locus characteristics, such as informativeness, scorability or distance to nearest neighbours. We used MultiMap to construct a human genetic map at an average resolution of 6 cM, using published genotypes at 1266 microsatelhto markers, and further extended this map by adding 397 VNTR and polymorphic gene markers.
REFERENCES
- Collins, F. Positional cloning: lets not call it reverse anymore. Nature Genet. 1, 3−6 (1992). | PubMed | ISI | ChemPort |
- Chakravarti, A. & Lander, E. in Banbury Report 33: Genetics and Biology of Alcoholism (eds. C.R. Cloninger & E. Begleiter) 307−315 (Cold Spring Harbor Press, New York, 1991).
- Weber, J.L. & May, P.E. Abundant class of human DMA polymorphisms which can be typed using the polymerase chain reaction. Am. J. hum. Genet. 44, 388−396 (1989). | PubMed | ISI | ChemPort |
- Litt, M. & Luty, J.A. A hypervariable microsatelllte revealed by in vitro amplification of a dlnucleotide repeat within the cardiac muscle actin gene. Am. J. hum. Genet. 44, 397−401 (1989). | PubMed | ISI | ChemPort |
- Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794−801 (1992). | Article | PubMed | ISI | ChemPort |
- NIH/CEPH Collaborative Mapping Group. A comprehensive genetic linkage map of the human genome. Science 258, 67−86 (1992). | ISI |
- Dietrich, W. et al. A genetic map of the mouse suitable for typing intraspeclfic crosses. Genetics 131, 423−447 (1992). | PubMed | ISI | ChemPort |
- Ziegle, J.S. et al. Application of automated DNA sizing technology for genotyping microsatellite loci. Genomics 14, 1026−1031 (1992). | PubMed | ISI | ChemPort |
- Vignal, A. et al. in Methods in Molecular Genetics, Volume 1: Gene and Chromosome Analysis 211−221 (ed. Adolph, K. W.) (Academic Press, New York, 1993). | ChemPort |
- Dausset, J. Lecentre d'étude du polymoiphisme humain. La Presse Médicale 15, 1801−1802 (1986). | ChemPort |
- Ott, J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am. J. hum. Genet. 26, 588−597 (1974). | PubMed | ISI | ChemPort |
- 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 |
- Lander, E.S. et al. MAPMAKER: An interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1, 174−181 (1987). | PubMed | ChemPort |
- Lander, E.S. & Green, P. Construction of multi-locus genetic linkage maps in humans. Proc. natn. Acad. Sci. U.S.A. 84, 2363−2367 (1987). | ChemPort |
- Lange, K., Weeks, D. & Boehnke, M. Programs for pedigree analysis: MENDEL, FISHER and dGENE. Genet. Epidemiol. 5, 471−472 (1988). | PubMed | ISI | ChemPort |
- Buchanan, B.G. & Smith, R.G. Fundamentals of expert systems. Ann. Rev. Comput. Sci. 3, 23−58 (1988). | Article | ISI |
- Keats, B.J.B. et al. Guidelines for human linkage maps: an international system for human linkage maps (ISLM, 1990). Genomics 9, 557−560 (1991). | PubMed | ISI | ChemPort |
- Weeks, D.E. in Advanced Techniques in Chromosome Research (ed. K.W. Adolph) 297−330 (Marcel Dekker, New York, 1991). | ChemPort |
- OConnell, P. et al. A primary genetic linkage map for human chromosome 12. Genomics 1, 93−102 (1987). | PubMed | ChemPort |
- Barker, D. et al. A genetic linkage map of 63 DNA markers on chromosome 7. Proc. natn. Acad. Sci. U.S.A. 84, 8006−8010 (1987). | ChemPort |
- Buetow, K.H. et al. A detailed map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates. Am. J. hum. Genet. 48, 911−925 (1991). | PubMed | ISI | ChemPort |
- Donis-Keller, H. et al. A genetic linkage map of the human genome. Cell 5l, 319−337 (1987). | Article |
- Cox, T.K., Perlin, M. & Chakravarti, A. MultiMap: Automatic construction of linkage maps. Am. J. hum. Genet. 51 (Suppl.), A33 (1992).
- Cox, T.K. Automated genetic linkage mapping: development and performance assessment of an expert system computer program. (Ph. D. dissertation, University of Pittsburgh, 1992).
- Lupski, J.R. et al. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell 66, 219−232 (1991). | PubMed | ISI | ChemPort |
- Buetow, K.H. Influence of aberrant observations on high-resolution linkage analysis outcomes. Am. J. hum. Genet. 49, 985−994 (1991). | PubMed | ISI | ChemPort |
- Lasher, L., Reefer, J. & Chakravarti, A. Effects of genotyping errors on the estimation of chromosome map length. Am. J. hum. Genet. 49, 369 (1991). | ISI |
- Chakravarti, A. Information content of the Centre dEtude du Polymorphisme Humain (CEPH) family structures for linkage studies. Hum. Genet. 87, 721−724 (1991). | PubMed | ISI | ChemPort |
- 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. 32, 314−331 (1980). | PubMed | ISI | ChemPort |
- Chakravarti, A., Lasher, L.K. & Reefer, J.E. A maximum likelihood method for estimating genome length using linkage data. Genetics 128, 175−182 (1991). | PubMed | ISI | ChemPort |
- Mclnnis, M.G. et al. A linkage map of human chromosome 21: 43 PCR markers at average intervals of 2.5 cM. Genomics 16, 562−571 (1993). | Article | PubMed | ISI | ChemPort |
- Engelstein, M. et al. A PCR based linkage map of human chromosome 1. Genomics 15, 251−258 (1993). | Article | PubMed | ISI | ChemPort |
- Hong, H.-K., Giorda, R., Trucco, M. & Chakravarti, A. Dinucleotlde repeat polymorphisms at the DT3S192 and D73SJ93 loci. Hum. molec. Genet. 2, 86 (1992). | ISI |
- Hong, H.-K., Giorda, R., Yu, L.M., Trucco, M. & Chakravarti, A. A microsatellite repeat polymorphism at the D13S197 locus. Hum. molec. Genet. 2, 337 (1992). | ISI |
- Morton, N.E. Parameters of the human genome. Proc. natn Acad. Sci. U.S.A. 88, 7474−7476 (1991). | ChemPort |
- Weissenbach, J. et al. Improving the resolution of the Genethon genetic linkage map. In Genome Mapping and Sequencing, 199 (Cold Spring Harbor Press, Cold Spring Harbor Laboratory, 1993).
- Cox, D.R., Burmelster, M., Price, E.R., Kim, S. & Myers, R.M. Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 250, 245−250 (1990). | PubMed | ISI | ChemPort |
- Green, P. Genetic Analysis Workshop 7: Issues in gene mapping and detection of major genes. (eds MacCluer, J.W. et al.) Cytogenet. Cell Genet. 59, 122 (1992). | PubMed | ISI | ChemPort |
- Chakravarti, A. & Reefer, J.E. Genetic Analysis Workshop 7: Issues in gene mapping and detection of major genes. (eds MacCluer, J.W. et al.) Cytogenet. Cell Genet. 59, 99 (1992). | Article | PubMed | ISI | ChemPort |
- Chakravarti, A. A graphical representation of genetic and physical maps: the Marey map. Genomics 11, 219−222 (1991). | PubMed | ISI | ChemPort |
- Matise, T.C., Blaschak, J.E., Kompanek, A.J., Weeks, D.E. & Chakravarti, A. Patterns of sex-difference and interference in the human genome. Am. J. hum. Genet. 53, 262 (1993). | ISI |
- Buetow, K.H. & Chakravarti, A. Multipoint gene mapping using seriation II. Analysis of simulated and empirical data. Am. J. hum. Genet. 41, 189−201 (1987). | PubMed | ISI | ChemPort |
- Steele, G.L. Common Lisp: The Language. Digital Press, Burlington, Massachusetts (1984).
- LUCID Inc. Lucid Common Lisp/Sparc. (Menlo Park, Califomia, 1990).
- Carnegie Mellon University. Carnegie Mellon Common Lisp (CMU CL). (Pittsburgh, Pennsylvania, 1992).
- Cuttichia, A., Fasman, K., Kingsbury, D., Robbins, R. & Pearson, P. The GDBTM Human Genome Data Base 1993. Nucl. Acids Res. 21, 3003−3006 (1993). | PubMed | ISI |
|
