Dataset Information

Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population.

ABSTRACT: In genetics the ability to accurately describe the familial relationships among a group of individuals can be very useful. Recent statistical tools succeeded in assessing the degree of relatedness up to 6-7 generations with good power using dense genome-wide single-nucleotide polymorphism data to estimate the extent of identity-by-descent (IBD) sharing. It is therefore important to describe genome-wide patterns of IBD sharing for more remote and complex relatedness between individuals, such as that observed in a founder population like Quebec, Canada. Taking advantage of the extended genealogical records of the French Canadian founder population, we first compared different tools to identify regions of IBD in order to best describe genome-wide IBD sharing and its correlation with genealogical characteristics. Results showed that the extent of IBD sharing identified with FastIBD correlates best with relatedness measured using genealogical data. Total length of IBD sharing explained 85% of the genealogical kinship's variance. In addition, we observed significantly higher sharing in pairs of individuals with at least one inbred ancestor compared with those without any. Furthermore, patterns of IBD sharing and average sharing were different across regional populations, consistent with the settlement history of Quebec. Our results suggest that, as expected, the complex relatedness present in founder populations is reflected in patterns of IBD sharing. Using these patterns, it is thus possible to gain insight on the types of distant relationships in a sample from a founder population like Quebec.

SUBMITTER: Gauvin H

PROVIDER: S-EPMC4023206 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population.

Gauvin Héloïse H Moreau Claudia C Lefebvre Jean-François JF Laprise Catherine C Vézina Hélène H Labuda Damian D Roy-Gagnon Marie-Hélène MH

European journal of human genetics : EJHG 20131016 6

In genetics the ability to accurately describe the familial relationships among a group of individuals can be very useful. Recent statistical tools succeeded in assessing the degree of relatedness up to 6-7 generations with good power using dense genome-wide single-nucleotide polymorphism data to estimate the extent of identity-by-descent (IBD) sharing. It is therefore important to describe genome-wide patterns of IBD sharing for more remote and complex relatedness between individuals, such as t ...[more]

PMID: 24129432

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Project description:Founder events play a critical role in shaping genetic diversity, fitness and disease risk in a population. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods require large sample sizes or phased genomes. Thus, we developed ASCEND that measures the correlation in allele sharing between pairs of individuals across the genome to infer the age and strength of founder events. We show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios. We then apply ASCEND to two species with contrasting evolutionary histories: ~460 worldwide human populations and ~40 modern dog breeds. In humans, we find that over half of the analyzed populations have evidence for recent founder events, associated with geographic isolation, modes of sustenance, or cultural practices such as endogamy. Notably, island populations have lower population sizes than continental groups and most hunter-gatherer, nomadic and indigenous groups have evidence of recent founder events. Many present-day groups--including Native Americans, Oceanians and South Asians--have experienced more extreme founder events than Ashkenazi Jews who have high rates of recessive diseases due their known history of founder events. Using ancient genomes, we show that the strength of founder events differs markedly across geographic regions and time--with three major founder events related to the peopling of Americas and a trend in decreasing strength of founder events in Europe following the Neolithic transition and steppe migrations. In dogs, we estimate extreme founder events in most breeds that occurred in the last 25 generations, concordant with the establishment of many dog breeds during the Victorian times. Our analysis highlights a widespread history of founder events in humans and dogs and elucidates some of the demographic and cultural practices related to these events.

Project description:The French Canadian population of Quebec is a unique, well-known founder population with religious, linguistic, and geographic isolation. The genetics of retinitis pigmentosa (RP) in Quebec is not well studied thus far. The purpose of our study was to establish the genetic architecture of autosomal dominant RP (adRP) and to characterize the phenotypes associated with new adRP mutations in Quebec.Sanger sequencing of the commonly mutated currently known adRP genes was performed in a clinically well-characterized cohort of 60 adRP French Canadian families. Phenotypes were analyzed by projected visual acuity (best corrected), Goldmann visual fields, optical coherence tomography (OCT), fundus autofluorescence (FAF), and ERG. The potential effect of the novel mutations was assessed using in silico bioinformatic tools. The pathogenicity of all variants was then confirmed by segregation analysis within the families, when available.We identified the causal mutation/gene in 24 of our adRP families, as 24 (40%) of 60 patients had adRP mutations in six known adRP genes. Eleven (46%) of these mutations were in RHO, four mutations (17%) were found in SNRNP200, three mutations (12.5%) in PRPH2/RDS, three mutations (12.5%) in TOPORS, two mutations (8%) in PRPF31, and one mutation (4%) in IMPDH1. Four mutations were novel. We identified new mutations in RHO (p.S270I), PRPF31 (p.R288W), IMPDH1 (p.Q318H), and TOPORS (p.H889R); the rest were previously reported. We present the genotype-phenotype characteristics of the four novel missense mutations.This is the first large screening of adRP genes in the founder population of Quebec. Our prevalence of known adRP genes is 40% in the French Canadian population, which is lower than in other adRP populations around the world, illustrating the uniqueness of the French Canadian population. Our findings are crucial in expanding the current understanding of the genotypic-phenotypic spectrum of RP and documenting the genetic architecture of our founder population.

Dataset Information

Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population.

Publications

Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population.

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