Journal Article

Recurrent rearrangements in the proximal 15q11–q14 region: a new breakpoint cluster specific to unbalanced translocations

Krajewska-Walasek, Malgorzata, Mattei, Marie-Geneviève, Croquette, Marie-Françoise, Moncla, Anne, Depetris, Danielle, Delobel, Bruno, Mignon-Ravix, Cécile, Missirian, Chantal, Luciani, Judith J, Cuoco, Cristina, Collignon, Patrick, Kroisel, Peter M

2007

Overview

Unbalanced translocations, that involve the proximal chromosome 15 long arm and the telomeric region of a partner chromosome, result in a karyotype of 45 chromosomes with monosomy of the proximal 15q imprinted region. Here, we present our analysis of eight such unbalanced translocations that, depending on the parental origin of the rearranged chromosome, were associated with either Prader–Willi or Angelman syndrome. First, using FISH with specific BAC clones, we characterized the chromosome 15 breakpoint of each translocation and demonstrate that four of them are clustered in a small 460 kb interval located in the proximal 15q14 band. Second, analyzing the sequence of this region, we demonstrate the proximity of a low-copy repeat 15 (LCR15)-duplicon element that is known to facilitate recombination events at meiosis and to promote rearrangements. The presence, in this region, of both a cluster of translocation breakpoints and a LCR15-duplicon element defines a new breakpoint cluster (BP6), which, to our knowledge, is the most distal breakpoint cluster described in proximal 15q. Third, we demonstrate that the breakpoints for other rearrangements including large inv dup (15) chromosomes do not map to BP6, suggesting that it is specific to translocations. Finally, the translocation breakpoints located within BP6 result in very large proximal 15q deletions providing new informative genotype–phenotype correlations.

• Publisher: Springer International Publishing,Nature Publishing,Nature Publishing Group
• Subject: Adult / Angelman Syndrome - genetics / Bacterial artificial chromosomes / Bioinformatics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Breakpoints / Child / Child, Preschool / Chromosome 15 / Chromosome aberrations / Chromosome Breakage / Chromosome Mapping / Chromosome translocations / Chromosomes / Chromosomes, Human, Pair 15 - genetics / Cytogenetics / Female / Fundamental and applied biological sciences. Psychology / Gene Expression / General aspects. Genetic counseling / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genotype & phenotype / Genotypes / Human Genetics / Humans / In Situ Hybridization, Fluorescence / Infant / Infant, Newborn / Intellectual disabilities / Karyotyping / Male / Medical genetics / Medical sciences / Meiosis / Molecular and cellular biology / Monosomy / Phenotypes / Prader-Willi syndrome / Prader-Willi Syndrome - genetics / Recombination / Repetitive Sequences, Nucleic Acid - genetics / Telomere - genetics / Translocation, Genetic - genetics