title: Direct visualization of the highly polymorphic RNU2 locus in proximity to the BRCA1 gene.
abstract: Although the breast cancer susceptibility gene BRCA1 is one of the most extensively characterized genetic loci, much less is known about its upstream variable number tandem repeat element, the RNU2 locus. RNU2 encodes the U2 small nuclear RNA, an essential splicing element, but this locus is missing from the human genome assembly due to the inherent difficulty in the assembly of repetitive sequences. To fill the gap between RNU2 and BRCA1, we have reconstructed the physical map of this region by re-examining genomic clone sequences of public databases, which allowed us to precisely localize the RNU2 array 124 kb telomeric to BRCA1. We measured by performing FISH analyses on combed DNA for the first time the exact number of repeats carried by each of the two alleles in 41 individuals and found a range of 6-82 copies and a level of heterozygosity of 98%. The precise localisation of the RNU2 locus in the genome reference assembly and the implementation of a new technical tool to study it will make the detailed exploration of this locus possible. This recently neglected macrosatellite could be valuable for evaluating the potential role of structural variations in disease due to its location next to a major cancer susceptibility gene.
authors.affiliation: «Genetics of Breast Cancer» team, Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France ; Genomic Vision, Bagneux, Paris, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Tessereau
authors.forename: Monique
authors.initials: M
authors.lastname: Buisson
authors.forename: Nastasia
authors.initials: N
authors.lastname: Monnet
authors.forename: Marine
authors.initials: M
authors.lastname: Imbert
authors.forename: Laure
authors.initials: L
authors.lastname: Barjhoux
authors.forename: Caroline
authors.initials: C
authors.lastname: Schluth-Bolard
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Conseiller
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceppi
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure*; D005260:Female; D015870:Gene Expression; D019398:Genes, BRCA1; D056426:Genetic Loci; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018895:Microsatellite Repeats; D020161:Physical Chromosome Mapping; D012342:RNA, Small Nuclear / Q000235:genetics*
chemical_list: D012342:RNA, Small Nuclear; C405484:U2 small nuclear RNA