A BRCA1 founder mutation, identified with haplotype analysis, allowing genotype/phenotype determination and predictive testing

Dørum, Anne; Møller, Pål; Kamsteeg, Erik Jan; Scheffer, Hans; Burton, M.; Heimdal, Ketil; Mæhle, Lovise; Hovig, Eivind; Tropé, Claes G.; Hout, Annemarie H. van der; Meulen, M.A. van der; Buys, Chcm; Meerman, Gjt

doi:10.1016/s0959-8049(97)00328-6

Cited by 24 publications

(17 citation statements)

References 15 publications

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“…In Ashkenazi Jews, three recurrent founder mutations have been shown to be present at higher frequency and account for a significant proportion of the hereditary breast and ovarian cancer cases in this population. (38–41) Founder BRCA mutations have also been identified in families from Iceland (42–44), Poland (45, 46), Quebec (47, 48), Great-Britain (49), Netherlands (50, 51), Norway (52), Russia (53), and Sweden (54), among others. Based on those observations, a simplified screening panel has been developed for initial mutation analyses in some of those populations.…”

Section: Discussionmentioning

confidence: 99%

Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico

et al. 2012

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Mutations in the breast cancer 1, early onset (BRCA1) and breast cancer 2 (BRCA2) genes are responsible for the majority of hereditary breast cancers. Knowledge of the incidence and prevalence of BRCA mutations in a specific population or ethnic group is necessary to provide accurate genetic counseling for breast cancer patients and their families. However, these data have not been gathered in the population of Puerto Rico. We conducted a retrospective study of female breast cancer patients undergoing genetic testing for BRCA mutations in the highest volume breast surgery practices in San Juan, Puerto Rico. Data collection includes 3-generation family cancer history and results from complete BRCA sequencing. A total of 6 different deleterious mutations were observed, including 1 mutation in BRCA1 and 5 mutations in BRCA2. Three recurrent mutations (BRCA1 del exon1–2, BRCA2 4150G>T, and BRCA2 6027del4) account for over 70% of all the BRCA mutations observed in this study population. This study examines for the first time the characteristics of hereditary breast cancer in Puerto Rico, and assesses the accuracy of existing genetic risk assessment tools in that population. This data is expected to contribute to providing accurate and efficient tools for the clinical management of hereditary breast cancer in Puerto Rico.

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Section: Discussionmentioning

confidence: 99%

Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico

et al. 2012

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“…They mapped a new gene for benign recurrent intrahepatic cholestasis, a rare autosomal recessive disease, in sample that consisted of only three patients. This approach was further developed by te Meerman et al [12] and Van der Meulen and te Meerman [16] in the framework of population-based association studies, and yielded a method they called the Haplotype Sharing Statistics (HSS) [11,17] , and has been applied successfully to simulated data [18][19][20] as well as in gene mapping studies of breast cancer [21] , multiple sclerosis [22] , asthma [23] , testicular carcinoma [24] , and psoriasis [25] . Various methods for association studies using haplotype sharing have been developed for both case-control and family-based studies [26][27][28][29][30] .…”

Section: Introductionmentioning

confidence: 99%

Haplotype Sharing Analysis Using Mantel Statistics

et al. 2005

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Objective: The potential value of haplotypes has attracted widespread interest in the mapping of complex traits. Haplotype sharing methods take the linkage disequilibrium information between multiple markers into account, and may have good power to detect predisposing genes. We present a new approach based on Mantel statistics for spacetime clustering, which is developed in order to improve the power of haplotype sharing analysis for gene mapping in complex disease. Methods: The new statistic correlates genetic similarity and phenotypic similarity across pairs of haplotypes for case-only and case-control studies. The genetic similarity is measured as the shared length between haplotypes around a putative disease locus. The phenotypic similarity is measured as the mean-corrected cross-product based on the respective phenotypes. We analyzed two tests for statistical significance with respect to type I error: (1) assuming asymptotic normality, and (2) using a Monte Carlo permutation procedure. The results were compared to the χ² test for association based on 3-marker haplotypes. Results: The results of the type I error rates for the Mantel statistics using the permutational procedure yielded pointwise valid tests. The approach based on the assumption of asymptotic normality was seriously liberal. Conclusion:Power comparisons showed that the Mantel statistics were better than or equal to the χ² test for all simulated disease models.

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“…Many different mutations in BRCA1 have been identified in high-risk families with multiple cases of breast and ovarian cancer, and it is now well known that some recurrent mutations occur in specific populations Tonin et al 1995;Johannesdottir et al 1996; Thorlacius et al 1996;Gayther et al 1997;Peelen et al 1997;Petrij-Bosch et al 1997;Ramus et al 1997;Szabo and King 1997;Thorlacius et al 1997;Tonin et al 1998;Gorski et al 2000;Sarantaus et al 2001). In many instances, haplotype analysis of recurrent mutations has shown evidence of a founder effect, thus explaining the higher frequency of these mutations Berman et al 1996;Neuhausen et al 1996Neuhausen et al , 1998Dorum et al 1997;Liede et al 2000;Sarantaus et al 2000; Barkardottir et al 2001). Studies based on these founder populations have also proven useful to achieve characterization of these mutations.…”

Section: Introductionmentioning

confidence: 99%

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

et al. 2005

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The Quebec population contains about six-million French Canadians, descended from the French settlers who colonized "Nouvelle-France" between 1608 and 1765. Although the relative genetic contribution of each of these founders is highly variable, altogether they account for the major part of the contemporary French-Canadian gene pool. This study was designed to analyze the role of this founder effect in the introduction and diffusion of the BRCA1 recurrent R1443X mutant allele. A highly conserved haplotype, observed in 18 French-Canadian families and generated using 17 microsatellite markers surrounding the BRCA1 locus, supports the fact that the R1443X mutation is a founder mutation in the Quebec population. We also performed haplotyping analysis of R1443X carriers on 19 other families from seven different nationalities; although the same alleles are shared for three markers surrounding the BRCA1 gene, distinct haplotypes were obtained in four families, suggesting multiple origins for the R1443X mutation. Ascending genealogies of the 18 French Canadian families and of controls were reconstructed on an average depth of 10 generations. We identified the founder couple with the highest probability of having introduced the mutation in the population. Based on the descending genealogy of this couple, we detected the presence of geographical concentration in the diffusion pattern of the mutation. This study demonstrates how molecular genetics and demogenetic analyses can complement each other to provide findings that could have an impact on public health. Moreover, this approach is certainly not unique to breast cancer genetics and could be used to understand other complex traits.

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A BRCA1 founder mutation, identified with haplotype analysis, allowing genotype/phenotype determination and predictive testing

Cited by 24 publications

References 15 publications

Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico

Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico

Haplotype Sharing Analysis Using Mantel Statistics

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

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