High rates of de novo 15q11q13 inversions in human spermatozoa
Molina, Òscar (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Anton, Ester (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Vidal, Francesca (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Blanco, Joan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2012
Resum:	Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS) fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies. Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 region. Signal associations allowed the discrimination between normal and inverted haplotypes, which were confirmed by laser-scanning confocal microscopy. Two types of inversions were detected which correspond to the segments involved in Class I and II PWS deletions. No significant differences were observed in the mean frequencies of inversions between controls and PWS fathers (3. 59% ± 0. 46 and 9. 51% ± 0. 87 vs 3. 06% ± 0. 33 and 10. 07% ± 0. 74). Individual comparisons showed significant increases of inversions in four PWS fathers (P < 0. 05) previously reported as patients with increases of 15q11q13 deletions. Results suggest that the incidence of heterozygous inversion carriers in the general population could reach significant values. This situation could have important implications, as they have been described as predisposing haplotypes for genomic disorders. As a whole, results confirm the high instability of the 15q11-q13 region, which is prone to different types of de novo reorganizations by intrachromatid NAHR.
Ajuts:	Ministerio de Ciencia e Innovación SAF2010-22241
Nota:	Altres ajuts: This work was supported by the project CF-180034 (Universitat Autònoma de Barcelona). Oscar Molina is the recipient of a grant from the Universitat Autònoma de Barcelona (UAB/PIF2007).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Molecular Cytogenetics, Vol. 5 (February 2012) , art. 11, ISSN 1755-8166

DOI: 10.1186/1755-8166-5-11
PMID: 22309495

9 p, 1.3 MB

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