A LARGE POLYMORPHIC REPEAT IN THE PERICENTROMERIC REGION OF HUMAN-CHROMOSOME 15Q CONTAINS 3 PARTIAL GENE DUPLICATIONS

We report the identification of a partial duplication of GABRA5, a gen e within the imprinted 15q11-q13 region. The duplicated locus maps to the pericentromeric region of 15q, proximal to the large deletions ass ociated with Angelman and Prader-Willi syndromes. We also observed var iation in the number of copies of this locus in different individuals, indicating that the duplication is part of a variable repeat. Investi gation of the duplication in individuals with a normal karyotype revea led between one and four copies of the repeat on each chromosome 15, w hereas from eight to 20 copies were found in individuals possessing a cytogenetically detectable elongation of the 15q region. The variable region is roughly 1 Mb in size and contains two other non-processed du plications, the immunoglobulin heavy chain (IgH) D segment gene and th e neurofibromatosis type 1 (NF1) gene. One unit of the pericentromeric repeat is thus composed of duplications of genes from different chrom osomal regions. Moreover, we have found replication asynchrony across the GABRA5 du plication, suggesting for the first time that the imprin ted part of chromosome 15q extends proximal of the region commonly del eted in Angelman and Prader-Willi syndromes.