Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia.
Africa
/ epidemiology
BRCA1 Protein
/ genetics
Brazil
/ epidemiology
Breast Neoplasms
/ epidemiology
Chile
/ epidemiology
Chromosomes, Human, Pair 17
/ genetics
Colombia
/ epidemiology
Female
Founder Effect
Genetic Predisposition to Disease
Genome-Wide Association Study
/ methods
Germ-Line Mutation
Haplotypes
Humans
Polymorphism, Single Nucleotide
Portugal
/ epidemiology
Spain
/ epidemiology
BRCA1 c.3331_3334delCAAG
Breast cancer
Founder mutation
Haplotype
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
01
04
2020
accepted:
16
09
2020
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
14
1
2021
Statut:
epublish
Résumé
The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.
Sections du résumé
BACKGROUND
The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry.
METHODS
BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia.
RESULTS
The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period.
CONCLUSIONS
Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.
Identifiants
pubmed: 33087180
doi: 10.1186/s13058-020-01341-3
pii: 10.1186/s13058-020-01341-3
pmc: PMC7579869
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108Subventions
Organisme : University of Tolima
ID : EOCYT
Pays : International
Organisme : GlaxoSmithKline foundation
ID : 10112
Pays : International
Organisme : Colciencias
ID : 755-2016
Pays : International
Organisme : Colciencias
ID : 647-2015
Pays : International
Organisme : CNPq
ID : 408313/2016-1
Pays : International
Organisme : CIBERER
ID : ER17P1AC7112/2017
Pays : International
Organisme : Colciencias
ID : 528-2011
Pays : International
Organisme : NIGMS NIH HHS
ID : R01 GM123306
Pays : United States
Organisme : Fondo de Fomento al Desarrollo Científico y Tecnológico
ID : CA12I10152
Pays : International
Investigateurs
Barbara Alemar
(B)
Cristina Brinckmann Oliveira Netto
(CBO)
Dirce Maria Carraro
(DM)
Fernando Regla Vargas
(FR)
Gustavo Stumpf da Silva
(GS)
Ivana Lúcia Oliveira Nascimento
(ILO)
Kelly Rose Lobo de Souza
(KRL)
Maria Isabel Achatz
(MI)
Miguel Angelo Martins Moreira
(MAM)
Maria Betânia Torrales
(MB)
Maristela Pimenta
(M)
Taisa Manuela Bonfim Machado-Lopes
(TMB)
Fernando Bolaños
(F)
Raúl Murillo
(R)
Yesid Sánchez
(Y)
Carolina Sanabria
(C)
Martha Lucia Serrano
(ML)
John Jairo Suarez
(JJ)
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