Identity by descent mapping of founder mutations in cancer using high-resolution tumor SNP data.

PloS One
Eric LetouzéAurélien de Reyniès

Abstract

Dense genotype data can be used to detect chromosome fragments inherited from a common ancestor in apparently unrelated individuals. A disease-causing mutation inherited from a common founder may thus be detected by searching for a common haplotype signature in a sample population of patients. We present here FounderTracker, a computational method for the genome-wide detection of founder mutations in cancer using dense tumor SNP profiles. Our method is based on two assumptions. First, the wild-type allele frequently undergoes loss of heterozygosity (LOH) in the tumors of germline mutation carriers. Second, the overlap between the ancestral chromosome fragments inherited from a common founder will define a minimal haplotype conserved in each patient carrying the founder mutation. Our approach thus relies on the detection of haplotypes with significant identity by descent (IBD) sharing within recurrent regions of LOH to highlight genomic loci likely to harbor a founder mutation. We validated this approach by analyzing two real cancer data sets in which we successfully identified founder mutations of well-characterized tumor suppressor genes. We then used simulated data to evaluate the ability of our method to detect IBD tracts as...Continue Reading

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Citations

Sep 26, 2012·Cellular and Molecular Life Sciences : CMLS·Ada ColluraAlex Duval
Sep 11, 2012·Human Molecular Genetics·Nelly BurnichonAnne-Paule Gimenez-Roqueplo
Oct 8, 2020·Scientific Reports·Carolina MathiasEnilze M F S Ribeiro
Jul 16, 2021·Genome Medicine·Kar-Tong TanAndrew L Hong

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Datasets Mentioned

BETA
GSE32206

Methods Mentioned

BETA
chip
genotyping

Software Mentioned

FounderTracker
Integrative Genomics Viewer
DNAcopy
Illumina BeadStudio
GERMLINE
Bioconductor
PresenceAbsence R package
DASH

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