Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

BMC Medical Genetics
Jacob L McCauleyJonathan L Haines

Abstract

Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD) susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes. We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS) method that compares identity by state (IBS) (under the presumption of identity by descent (IBD)) sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers. In all, 13 dementia cases and 14 normal controls were identified who were not relate...Continue Reading

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Citations

Jul 14, 2011·Human Genetics·Monique D CourtenayWilliam K Scott
May 10, 2013·PloS One·Anna C CummingsJonathan L Haines
Jan 24, 2007·Biochemical and Biophysical Research Communications·Norihiko SasakiShoko Nishihara
Feb 11, 2021·International Journal of Environmental Research and Public Health·Andrea R WaksmunskiJessica N Cooke Bailey

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Methods Mentioned

BETA
for
genotyping
PCR
fluorescence imaging

Software Mentioned

PedHunter
PedCheck
R
SimWalk2
Primer3
SAS

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