Authors
Alejandro Mejia-Garcia, Alex Diaz-Papkovich, Guillaume Sillon, Daniela D'Agostino, Anne-Laure Chong, George Chong, Ken Sin Lo, Laurence Baret, Nancy Hamel, Vincent Chapdelaine, William D Foulkes, Daniel Taliun, Adam J Shapiro, Guillaume Lettre, Simon Gravel
Published in
American journal of human genetics. Volume 112. Issue 12. Pages 2973-2981. Dec 04, 2025. Epub Oct 30, 2025.
Abstract
Gene genealogies represent the shared ancestry of a sample and are often encoded as ancestral recombination graphs (ARGs). It has recently become possible to infer these gene genealogies from sequencing or genotyping data and use them for many evolutionary and statistical genetics applications. Here, we use the ARG inference software ARG-needle and the pedigree imputation software ISGen to impute and trace the transmission of disease variants in founder populations where long shared haplotypes allow for accurate timing of relatedness. We applied these methods to the population of Quebec, where multiple founder events led to an uneven distribution of pathogenic variants across regions and where extensive population pedigrees are available via the BALSAC project. We validated this approach with nine founder mutations for the Saguenay-Lac-Saint-Jean region, demonstrating high accuracy for mutation age, imputation, and regional frequency estimation. We used imputed carrier status in a longitudinal cohort to highlight heterozygote effects for known recessive alleles. These heterozygote effects, together with regional frequency estimates, can inform the design of screening programs.
PMID:
41172993
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.
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