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The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations

BACKGROUND: Analysis of the chromosomal background upon which a mutation occurs can be used to reconstruct the origins of specific disease-causing mutations. The relatively common BRCA1 mutation, 1135insA, has been previously identified as a Norwegian founder mutation. We performed haplotype analysi...

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Autores principales: Rudkin, Teresa M, Hamel, Nancy, Galvez, Maria, Hogervorst, Frans, Gille, Johan JP, Møller, Pål, Apold, Jaran, Foulkes, William D
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1403746/
https://www.ncbi.nlm.nih.gov/pubmed/16509964
http://dx.doi.org/10.1186/1471-2350-7-15
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author Rudkin, Teresa M
Hamel, Nancy
Galvez, Maria
Hogervorst, Frans
Gille, Johan JP
Møller, Pål
Apold, Jaran
Foulkes, William D
author_facet Rudkin, Teresa M
Hamel, Nancy
Galvez, Maria
Hogervorst, Frans
Gille, Johan JP
Møller, Pål
Apold, Jaran
Foulkes, William D
author_sort Rudkin, Teresa M
collection PubMed
description BACKGROUND: Analysis of the chromosomal background upon which a mutation occurs can be used to reconstruct the origins of specific disease-causing mutations. The relatively common BRCA1 mutation, 1135insA, has been previously identified as a Norwegian founder mutation. We performed haplotype analysis of individuals from breast and ovarian cancer families from four different ethnic backgrounds who had been identified as carriers of the BRCA1: 1135insA mutation. METHODS: Four microsatellite markers (D17S855, D17S1322, D17S1323 and D17S1325) located within or near the BRCA1 gene were genotyped in mutation carriers from 6 families of French Canadian, Italian and Dutch descent. Haplotypes were inferred from the genotype data and compared between these families and with the previously reported Norwegian founder haplotype. RESULTS: The 1135insA mutation was found to occur on three distinct haplotype backgrounds. The families from Norway shared a distinct haplotype while the families of French Canadian, Italian, and Dutch descent were found to occur on one of two additional, distinct backgrounds. CONCLUSION: Our results indicate that while the Norwegian haplotype including 1135insA represents an ancient Norwegian mutation, the same mutation has occurred independently in the other populations examined. In centres where targeted mutation testing is performed, exclusively or prior to gene sequencing, our findings suggest that this recurring mutation should be included in targeted mutation panels, irrespective of the ethnic origin of the persons tested.
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spelling pubmed-14037462006-03-18 The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations Rudkin, Teresa M Hamel, Nancy Galvez, Maria Hogervorst, Frans Gille, Johan JP Møller, Pål Apold, Jaran Foulkes, William D BMC Med Genet Research Article BACKGROUND: Analysis of the chromosomal background upon which a mutation occurs can be used to reconstruct the origins of specific disease-causing mutations. The relatively common BRCA1 mutation, 1135insA, has been previously identified as a Norwegian founder mutation. We performed haplotype analysis of individuals from breast and ovarian cancer families from four different ethnic backgrounds who had been identified as carriers of the BRCA1: 1135insA mutation. METHODS: Four microsatellite markers (D17S855, D17S1322, D17S1323 and D17S1325) located within or near the BRCA1 gene were genotyped in mutation carriers from 6 families of French Canadian, Italian and Dutch descent. Haplotypes were inferred from the genotype data and compared between these families and with the previously reported Norwegian founder haplotype. RESULTS: The 1135insA mutation was found to occur on three distinct haplotype backgrounds. The families from Norway shared a distinct haplotype while the families of French Canadian, Italian, and Dutch descent were found to occur on one of two additional, distinct backgrounds. CONCLUSION: Our results indicate that while the Norwegian haplotype including 1135insA represents an ancient Norwegian mutation, the same mutation has occurred independently in the other populations examined. In centres where targeted mutation testing is performed, exclusively or prior to gene sequencing, our findings suggest that this recurring mutation should be included in targeted mutation panels, irrespective of the ethnic origin of the persons tested. BioMed Central 2006-03-01 /pmc/articles/PMC1403746/ /pubmed/16509964 http://dx.doi.org/10.1186/1471-2350-7-15 Text en Copyright © 2006 Rudkin et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rudkin, Teresa M
Hamel, Nancy
Galvez, Maria
Hogervorst, Frans
Gille, Johan JP
Møller, Pål
Apold, Jaran
Foulkes, William D
The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations
title The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations
title_full The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations
title_fullStr The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations
title_full_unstemmed The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations
title_short The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations
title_sort frequent brca1 mutation 1135insa has multiple origins: a haplotype study in different populations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1403746/
https://www.ncbi.nlm.nih.gov/pubmed/16509964
http://dx.doi.org/10.1186/1471-2350-7-15
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