How Old Is This Mutation? A Study of Three Ashkenazi Jewish Founder Mutations

摘要: Several founder mutations leading to increased risk of cancer among Ashkenazi Jewish individuals have been identified, and some estimates the age published. A variety different methods used previously estimate mutations. Here three datasets containing genotype information near known are reanalyzed in order compare approaches for estimating a mutation. The are: (a) single marker method by Risch et al., (1995); (b) intra-allelic coalescent model as DMLE, (c) Goldgar proposed Neuhausen al. (1996), modified slightly our group. analyzed were MSH2*1906 G->C, APC*I1307K, BRCA2*6174delT. All depend on accurate inter-marker recombination rates. allows mutation well recombination, but requires prior possible haplotypes carrying each individual. It does not incorporate population growth DMLE simultaneously with age, builds rate. estimates, however, more sensitive rates unstable. Mutation based 16.8 generations MSH2 (95% credible interval (13, 23)), 106 I1037K (86-129), 90 6174delT (71-114). For recent where unlikely occurred, both can give good results. Caution is necessary older mutations, especially if effective size may remained small long period time.