title: Evidence for an ancient BRCA1 mutation in breast cancer patients of Yoruban ancestry.
abstract: BACKGROUND
  BRCA1 recurrent mutations have rarely been assessed in non-founder populations. Still, identifying such mutations could be important for designing genetic testing strategies for high-risk breast/ovarian cancer families in non-founder populations.
  
  
  OBJECTIVE
  To determine whether the recurrent BRCA1 Y101X mutation identified in Yoruban breast cancer patients represents a single historical mutation event, and determine the prevalence of this mutation in a hospital based cohort.
  
  
  METHODS
  365 breast cancer patients and 177 controls of Yoruban ancestry from Nigeria, unselected for age of onset or family history were screened for the BRCA1 Y101X mutation. The haplotypes on which the Y101X mutation occurred were characterized using microsatellite markers and single-nucleotide polymorphisms (SNPs). Phase ambiguity was resolved using allele-specific PCR.
  
  
  RESULTS
  The BRCA1 Y101X mutation was detected in four Yoruban patients with no documented family history of breast cancer among a cohort of 365 (1.1, 95% C.I. = 0.43-2.78%) unrelated Yoruban breast cancer patients. This study reveals the four Y101X mutations occur on a single, rare haplotype. Further characterization in a patient of European ancestry with a strong family history of breast/ovarian cancer revealed the same Y101X mutation on the same haplotype as those in the Yoruban carriers. These observations suggest the Y101X mutations identified in the Yoruban patients may have originated from a single mutation event.
  
  
  CONCLUSIONS
  BRCA1 Y101X is the first reported recurrent mutation occurring in patients of African ancestry for which prevalence has been determined. Identification of this mutation in a woman of European ancestry with strong family history of breast/ovarian suggests further that this mutation occurred once, probably many generations ago.
authors.affiliation: Department of Medicine, Center for Clinical Cancer Genetics, University of Chicago, MC 2115, 5830 S Ellis Ave., Chicago, IL 60637, USA.
authors.forename: Bifeng
authors.initials: B
authors.lastname: Zhang
authors.forename: James D
authors.initials: JD
authors.lastname: Fackenthal
authors.forename: Qun
authors.initials: Q
authors.lastname: Niu
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Walmy E
authors.initials: WE
authors.lastname: Sveen
authors.forename: Tiffani
authors.initials: T
authors.lastname: DeMarco
authors.forename: Clement A
authors.initials: CA
authors.lastname: Adebamowo
authors.forename: Temidayo
authors.initials: T
authors.lastname: Ogundiran
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009549:Nigeria; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics