Abstract
We have developed a mathematical algorithm to implement a method for localizing mutations using haplotype analysis. Our strategy infers haplotypes based on the determination of genotypes of a proximal and a distal marker for 21 chromosomal intervals distributed across the mouse genome (corresponding to two intervals for Chromosomes (Chrs) 1 and 2 and one for the remaining 17 autosomes). To simulate the analysis of mice homozygous for recessive mutations, we tested the efficacy of our method on over 200 data sets generated from two independent mapping panel data sets containing the genotypes of 46 F2 progeny of an intercross and 94 F2 progeny of a backcross. In all cases we were able to identify the chromosomal interval carrying the recessive mutation despite the fact that some of the data sets consisted of as few as 10 meioses. Our strategy proved sensitive and expedient, since the simulated genome-wide screen could be executed by genotype analysis of 40 microsatellite markers in small numbers of intercross or backcross progeny.
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References
Carter TC, Falconer DS (1951) Stocks for detecting linkage in the mouse and the theory of their design. J Genet 50, 307–323
Dietrich W, Miller JC, Steen RG, Merchant M, Damron D, Hahf R, Gross A, Joyce DC, Wessel M, Dredge RD, Marquis A, Stein LD, Goodman N, Page DC, Lander ES (1994) A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nat Genet 7, 220–245
Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, Dredge RD, Daly MJ, Ingalls KA, O’Connor TJ, Evans CA, DeAngelis MM, Levinson DM, Kruglyak L, Goodman N, Copeland NG, Jenkins NA, Hawkins TL, Stein L, Page DC, Lander ES (1996) A comprehensive genetic map of the mouse genome (published erratum appears in Nature (1996). 381, 172). Nature 380, 149–152
Haidane JBS (1919) The combination of linkage values, and the calculation of distances between the loci of linked factors. J Genet 8, 299–309
Iakoubova OA, Dushkin H, Beier DR (1995) Localization of a murine recessive polycystic kidney disease mutation and modifying loci that affect disease severity. Genomics 26, 107–114
Lander E, Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11, 241–247
Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265, 2037–2048
Rowe LB, Nadeau JH, Turner R, Frankel WN, Letts VA, Eppig JT, Ko MS, Thurston SJ, Birkenmeier EH (1994) Maps from two interspecific backcross DNA panels available as a community genetic mapping resource (published erratum appears in Mamm Genome (1994) 5,463). Mamm Genome 5, 253–274
Silver LM (1995) In Mouse Genetics (New York, N.Y.: Oxford University Press, Inc.), pp 195–263
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Neuhaus, I.M., Beier, D.R. Efficient localization of mutations by interval haplotype analysis. Mammalian Genome 9, 150–154 (1998). https://doi.org/10.1007/s003359900706
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DOI: https://doi.org/10.1007/s003359900706