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Two classes of low‐copy repeats comediate a new recurrent rearrangement consisting of duplication at 8p23.1 and triplication at 8p23.2
Author(s) -
Giorda Roberto,
Ciccone Roberto,
Gimelli Giorgio,
Pramparo Tiziano,
Beri Silvana,
Bonaglia Maria Clara,
Giglio Sabrina,
Genuardi Maurizio,
Argente Jesùs,
Rocchi Mariano,
Zuffardi Orsetta
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20465
Subject(s) - biology , gene duplication , non allelic homologous recombination , dup , genetics , chromosomal inversion , chromosomal rearrangement , gene rearrangement , dicentric chromosome , chromosome , breakpoint , homologous recombination , fluorescence in situ hybridization , recombination , gene , genetic recombination , karyotype
We describe a new type of rearrangement consisting of the duplication of 8p23.1 and the triplication of 8p23.2 [dup trp(8p)] in two patients affected by mental retardation and minor facial dysmorphisms. Array–comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and genotyping of polymorphic loci allowed us to demonstrate that this rearrangement is mediated by the combined effects of two unrelated low‐copy repeats (LCRs). The first set of LCRs consists of the two clusters of olfactory receptor genes (OR‐REPs) lying at 8p23.1. The second type of LCRs consists of a 15‐kb segmental duplication, lying in inverted orientation at 8p23.2 and enclosing a nonrepeated sequence of approximately 130 kb, named MYOM2 ‐REP because of its proximity to the MYOM2 gene. The molecular characterization of a third case with a dicentric chromosome 8 demonstrated that the rearrangement had been generated by nonallelic homologous recombination between the two MYOM2 ‐REPs. Based on our findings, we propose a model showing that a second recombination event at the level of the OR‐REPs leads to the formation of the dup trp(8p) chromosome. This rearrangement can only arise during meiosis in heterozygous carriers of the polymorphic 8p23.1 inversion, whereas in subjects with noninverted chromosomes 8 or homozygous for the inversion only the dicentric chromosome can be formed. Our study demonstrates that nonallelic homologous recombination involving multiple LCRs can generate more complex rearrangements and cause a greater variety of genomic diseases. Hum Mutat 28(5), 459–468, 2007. © 2007 Wiley‐Liss, Inc.