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High rates of de novo 15q11q13 inversions in human spermatozoa

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...

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Autores principales: Molina, Òscar, Anton, Ester, Vidal, Francesca, Blanco, Joan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293048/
https://www.ncbi.nlm.nih.gov/pubmed/22309495
http://dx.doi.org/10.1186/1755-8166-5-11
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author Molina, Òscar
Anton, Ester
Vidal, Francesca
Blanco, Joan
author_facet Molina, Òscar
Anton, Ester
Vidal, Francesca
Blanco, Joan
author_sort Molina, Òscar
collection PubMed
description 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.
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spelling pubmed-32930482012-03-05 High rates of de novo 15q11q13 inversions in human spermatozoa Molina, Òscar Anton, Ester Vidal, Francesca Blanco, Joan Mol Cytogenet Research 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. BioMed Central 2012-02-06 /pmc/articles/PMC3293048/ /pubmed/22309495 http://dx.doi.org/10.1186/1755-8166-5-11 Text en Copyright ©2012 Molina et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Molina, Òscar
Anton, Ester
Vidal, Francesca
Blanco, Joan
High rates of de novo 15q11q13 inversions in human spermatozoa
title High rates of de novo 15q11q13 inversions in human spermatozoa
title_full High rates of de novo 15q11q13 inversions in human spermatozoa
title_fullStr High rates of de novo 15q11q13 inversions in human spermatozoa
title_full_unstemmed High rates of de novo 15q11q13 inversions in human spermatozoa
title_short High rates of de novo 15q11q13 inversions in human spermatozoa
title_sort high rates of de novo 15q11q13 inversions in human spermatozoa
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293048/
https://www.ncbi.nlm.nih.gov/pubmed/22309495
http://dx.doi.org/10.1186/1755-8166-5-11
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