Fine scale association mapping of disease loci using simplex families.
We present a new method for the fine scale mapping of disease loci based on samples of simplex families, each containing an affected child. The method is based on a generalisation of a single locus allele transmission model to multiple marker loci. The model is developed under the assumption of a single ancestral mutation and allows for the calculation of posterior probabilities that each allele at a particular marker was present on the founder chromosome. We illustrate the method using simulated family data for cystic fibrosis and Huntingtons disease, for which the locations of mutations in the disease genes are now known. For both diseases, our new method provides good estimates of the location of the mutations.
University of Reading, Department of Applied Statistics, PO Box 240, Earley Gate, Reading RG6 6FN, UK. sns98am@reading.ac.uk
A P
AP
Morris
J C
JC
Whittaker
D000483:Alleles; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D003550:Cystic Fibrosis / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D009679:Nuclear Family; D012984:Software
D005819:Genetic Markers