NDLI: How old is this mutation? - a study of three Ashkenazi Jewish founder mutations

Content Provider	Springer Nature : BioMed Central
Author	Greenwood, Celia MT Sun, Shuying Veenstra, Justin Hamel, Nancy Niell, Bethany Gruber, Stephen Foulkes, William D
Abstract	Background Several founder mutations leading to increased risk of cancer among Ashkenazi Jewish individuals have been identified, and some estimates of the age of the mutations have been published. A variety of different methods have been used previously to estimate the age of the mutations. Here three datasets containing genotype information near known founder mutations are reanalyzed in order to compare three approaches for estimating the age of a mutation. The methods are: (a) the single marker method used by Risch et al., (1995); (b) the intra-allelic coalescent model known as DMLE, and (c) the Goldgar method proposed in Neuhausen et al. (1996), and modified slightly by our group. The three mutations analyzed were MSH21906 G->C, APCI1307K, and BRCA2*6174delT. Results All methods depend on accurate estimates of inter-marker recombination rates. The modified Goldgar method allows for marker mutation as well as recombination, but requires prior estimates of the possible haplotypes carrying the mutation for each individual. It does not incorporate population growth rates. The DMLE method simultaneously estimates the haplotypes with the mutation age, and builds in the population growth rate. The single marker estimates, however, are more sensitive to the recombination rates and are unstable. Mutation age estimates based on DMLE are 16.8 generations for MSH2 (95% credible interval (13, 23)), 106 generations for I1037K (86-129), and 90 generations for 6174delT (71-114). Conclusions For recent founder mutations where marker mutations are unlikely to have occurred, both DMLE and the Goldgar method can give good results. Caution is necessary for older mutations, especially if the effective population size may have remained small for a long period of time.
Related Links	https://bmcgenomdata.biomedcentral.com/counter/pdf/10.1186/1471-2156-11-39.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	27306844
DOI	10.1186/1471-2156-11-39
Journal	BMC Genomic Data
Issue Number	1
Volume Number	11
Language	English
Publisher	BioMed Central
Publisher Date	2010-05-14
Access Restriction	Open
Subject Keyword	Life Sciences Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Genetics and Population Dynamics Credible Interval Founder Mutation Recent Common Ancestor Gene Genealogy Coalescent Time
Content Type	Text
Resource Type	Article
Subject	Health Informatics Genetics
Journal Impact Factor	1.9/2023
5-Year Journal Impact Factor	1.9/2023

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