Effets fondateurs et variabilité génétique au Québec

Moreau, Claudia; Vézina, Hélène; Labuda, Damian

doi:10.1051/medsci/200723111008

Cited by 13 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The genetic heterogeneity observed in BRIP1 variant carriers is consistent with the germline genetic landscape of the FC population of Quebec (3). The differences in carrier frequencies of our variants in BRIP1 as well as those observed in BRCA1, BRCA2, PALB2, RAD51C and RAD51D are expected in FCs and consistent with the genetic drift that has been attributed to the waves of localized expansion of this population that occurred in Quebec since 1608 (102)(103)(104). Given the European ancestry of FCs, it is not surprising that all five candidate BRIP1 variants were also identified in the germline of cancer cases in the literature (see Figure 1-B).…”

Section: Discussionsupporting

confidence: 81%

Genetic and molecular analyses of candidate germlineBRIP1/FANCJvariants implicated in breast and ovarian cancer

Milano,

Alenezi,

Fierheller

et al. 2023

Preprint

View full text Add to dashboard Cite

Five rare variants in BRIP1/FANCJ, initially reported in ovarian (OC) or breast (BC) cancer cases by the adult hereditary cancer clinics, were investigated for their candidacy as clinically relevant variants. These variants were investigated genetically in a population exhibiting genetic drift and molecularly assayed for biological impact. Using in silico tools, population-based genetic databases and other resources, three of the five reported BRIP1 variants were likely to be damaging: c.797C>T; p.Thr266Met, c.2087C>T; p.Pro696Leu and c.2990_2993delCAAA; p.Thr997ArgfsTer61. The carrier frequencies ranged from 0-0.7% in ancestry defined cancer groups comprised of 47 OC families, 49 hereditary breast and ovarian cancer, 142 hereditary breast cancer syndrome families, 435 sporadic OC cases and 563 sporadic BC cases and 0-0.2% in 1025 population-matched controls. Multiple carriers of the same variants were identified in additional cancer cases. Of the five reported BRIP1 variants, p.Thr266Met, p.Pro696Leu and p.Thr997ArgfsTer61, which were predicted to be damaging, conferred cellular sensitivity to mitomycin C and cisplatin unlike p.Ser139Ala and p.Ala406Ser. Collectively, our investigation implicates BRIP1 c.797C>T; p.Thr266Met, c.2087C>T; p.Pro696Leu and p.Thr997ArgfsTer61 as deleterious variants in OC and BC.

show abstract

Section: Discussionsupporting

confidence: 81%

Genetic and molecular analyses of candidate germlineBRIP1/FANCJvariants implicated in breast and ovarian cancer

Milano,

Alenezi,

Fierheller

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…While participants of the two cohorts are Caucasian of European ancestry, we might have expected differences between groups in the prevalence of the GLP1R A316T polymorphism due to the known founder effect in the French Canadian population [35]. In fact, in the Province of Quebec, the history of colonization and its consequences on the population's genetic heritage impacts the prevalence and/or clinical characteristics of some genetic diseases [36].…”

Section: Discussionmentioning

confidence: 99%

Association between the GLP1R A316T Mutation and Adolescent Idiopathic Scoliosis in French Canadian and Italian Cohorts

Normand,

Franco,

Parent

et al. 2024

Genes

View full text Add to dashboard Cite

Studies have revealed anthropometric discrepancies in girls with adolescent idiopathic scoliosis (AIS) compared to non-scoliotic subjects, such as a higher stature, lower weight, and lower body mass index. While the causes are still unknown, it was proposed that metabolic hormones could play a role in AIS pathophysiology. Our objectives were to evaluate the association of GLP1R A316T polymorphism in AIS susceptibility and to study its relationship with disease severity and progression. We performed a retrospective case–control association study with controls and AIS patients from an Italian and French Canadian cohort. The GLP1R rs10305492 polymorphism was genotyped in 1025 subjects (313 non-scoliotic controls and 712 AIS patients) using a validated TaqMan allelic discrimination assay. Associations were evaluated by odds ratio and 95% confidence intervals. In the AIS group, there was a higher frequency of the variant genotype A/G (4.2% vs. 1.3%, OR = 3.40, p = 0.016) and allele A (2.1% vs. 0.6%, OR = 3.35, p = 0.017) than controls. When the AIS group was stratified for severity (≤40° vs. >40°), progression of the disease (progressor vs. non-progressor), curve type, or body mass index, there was no statistically significant difference in the distribution of the polymorphism. Our results support that the GLP1R A316T polymorphism is associated with a higher risk of developing AIS, but without being associated with disease severity and progression.

show abstract

“…Our study evaluated rare variants in NPC1 and NPC2 genes in a sample from the Quebec population in Canada. This population is unique given the important founder effect from French colonisation in the early seventeenth century 28 . We had 911 RNA samples and 198 exome samples, with an overlap of 93 individuals.…”

Section: Discussionmentioning

confidence: 99%

Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec

Touma

Labrecque

Tétreault

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Niemann–Pick disease type C (NPC) is a treatable autosomal recessive neurodegenerative condition which leads to a variety of progressive manifestations. Despite most cases being diagnosed at a young age, disease prevalence may be underestimated, especially in adults, and interpretation of NPC1 and NPC2 variants can be difficult. This study aims to identify potential pathogenic variants in a large cohort of healthy individuals and classify their risk of pathogenicity to assist with future interpretation of variants. The CARTaGENE (CaG) cohort was used to identify possible variants of NPC1 and NPC2. Nine-hundred and eleven RNA samples and 198 exome sequencing were screened for genetic variants through a bio-informatic pipeline performing alignment and variant calling. The identified variants were analyzed using annotations for allelic frequency, pathogenicity and conservation scores. The ACMG guidelines were used to classify the variants. These were then compared to existing databases and previous studies of NPC prevalence, including the Tübingen NPC database. Thirty-two distinct variants were identified after running the samples in the RNA-sequencing pipeline, two of which were classified as pathogenic and 21 of which were not published previously. Furthermore, 46 variants were both identified in our population and with the Tübingen database, the majority of which were of uncertain significance. Ten additional variants were found in our exome-sequencing sample. This study of a sample from a population living in Quebec demonstrates a variety of rare variants, some of which were already described in the literature as well as some novel variants. Classifying these variants is arduous given the scarcity of available literature, even so in a population of healthy individuals. Yet using this data, we were able to identify two pathogenic variants within our population and several new variants not previously identified.

show abstract

Effets fondateurs et variabilité génétique au Québec

Cited by 13 publications

References 20 publications

Genetic and molecular analyses of candidate germlineBRIP1/FANCJvariants implicated in breast and ovarian cancer

Genetic and molecular analyses of candidate germlineBRIP1/FANCJvariants implicated in breast and ovarian cancer

Association between the GLP1R A316T Mutation and Adolescent Idiopathic Scoliosis in French Canadian and Italian Cohorts

Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec

Contact Info

Product

Resources

About