Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers
DiGeorge/velocardiofacial syndrome (DGS/VCFS) is the most common deletion syndrome in humans. Low copy repeats flanking the 22q11.2 region confer a substrate for non-allelic homologous recombination (NAHR) events leading to rearrangements. This study sought to identify DGS/VCFS fathers with increase...
| Authors: | ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2014 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/218093 |
| Online Access: | https://hdl.handle.net/2445/218093 |
| Access Level: | Open access |
| Keyword: | Anomalies cromosòmiques Seqüència de nucleòtids Espermatozoides Chromosome abnormalities Nucleotide sequence Spermatozoa |
| _version_ | 1878735375925510144 |
|---|---|
| author | Vergés, Laia |
| author2 | Molina, Òscar Geán, Esther Vidal, Francesca Blanco, J. (Joan) |
| author2_role | author author author author |
| author_browse | Blanco, J. (Joan) Geán, Esther Molina, Òscar Vergés, Laia Vidal, Francesca |
| author_facet | Vergés, Laia Molina, Òscar Geán, Esther Vidal, Francesca Blanco, J. (Joan) |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | DiGeorge/velocardiofacial syndrome (DGS/VCFS) is the most common deletion syndrome in humans. Low copy repeats flanking the 22q11.2 region confer a substrate for non-allelic homologous recombination (NAHR) events leading to rearrangements. This study sought to identify DGS/VCFS fathers with increased susceptibility to deletions and duplications at the 22q11.2 region in spermatozoa and to assess the particular contribution of intra-chromatid and/or inter-chromatid NAHR. Semen samples from nine DGS/VCFS fathers were analyzed by triple-color FISH using a probe combination that discriminated between normal, deleted and duplicated genotypes. Microsatellite analysis were performed in the parents and the affected children to determine the parental origin of the deleted chromosome 22. Results: A significant increase in 22q11.2 deletions was observed in the sperm of two out of nine DGS/VCFS fathers (odds ratio 2.03-fold, P < 0.01), and in both cases the deletion in the offspring was transmitted by the father. Patients with significant increases in sperm anomalies presented a disturbed deletion:duplication 1:1 ratio (P < 0.01). Conclusions: Altogether, results support that intra-chromatid NAHR is the mechanism responsible for the higher rate of sperm deletions, which is directly related to the transmission of the deleted chromosome 22 to offspring. Accordingly, the screening of sperm anomalies in the 22q11.2 region should be taken into account in the genetic counseling of DGS/VCFS families. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_7b7cfe4bc6efdf904643035be9dc8564 |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/218093 |
| publishDate | 2014 |
| publishDateSort | 2014 |
| publisher | BioMed Central |
| publisherStr | BioMed Central |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers Vergés, Laia Molina, Òscar Geán, Esther Vidal, Francesca Blanco, J. (Joan) Anomalies cromosòmiques Seqüència de nucleòtids Espermatozoides Chromosome abnormalities Nucleotide sequence Spermatozoa DiGeorge/velocardiofacial syndrome (DGS/VCFS) is the most common deletion syndrome in humans. Low copy repeats flanking the 22q11.2 region confer a substrate for non-allelic homologous recombination (NAHR) events leading to rearrangements. This study sought to identify DGS/VCFS fathers with increased susceptibility to deletions and duplications at the 22q11.2 region in spermatozoa and to assess the particular contribution of intra-chromatid and/or inter-chromatid NAHR. Semen samples from nine DGS/VCFS fathers were analyzed by triple-color FISH using a probe combination that discriminated between normal, deleted and duplicated genotypes. Microsatellite analysis were performed in the parents and the affected children to determine the parental origin of the deleted chromosome 22. Results: A significant increase in 22q11.2 deletions was observed in the sperm of two out of nine DGS/VCFS fathers (odds ratio 2.03-fold, P < 0.01), and in both cases the deletion in the offspring was transmitted by the father. Patients with significant increases in sperm anomalies presented a disturbed deletion:duplication 1:1 ratio (P < 0.01). Conclusions: Altogether, results support that intra-chromatid NAHR is the mechanism responsible for the higher rate of sperm deletions, which is directly related to the transmission of the deleted chromosome 22 to offspring. Accordingly, the screening of sperm anomalies in the 22q11.2 region should be taken into account in the genetic counseling of DGS/VCFS families. BioMed Central https://hdl.handle.net/2445/218093 |
| spellingShingle | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers Vergés, Laia Anomalies cromosòmiques Seqüència de nucleòtids Espermatozoides Chromosome abnormalities Nucleotide sequence Spermatozoa |
| status_str | publishedVersion |
| title | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers |
| title_full | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers |
| title_fullStr | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers |
| title_full_unstemmed | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers |
| title_short | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers |
| title_sort | Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers |
| topic | Anomalies cromosòmiques Seqüència de nucleòtids Espermatozoides Chromosome abnormalities Nucleotide sequence Spermatozoa |
| topic_facet | Anomalies cromosòmiques Seqüència de nucleòtids Espermatozoides Chromosome abnormalities Nucleotide sequence Spermatozoa |
| url | https://hdl.handle.net/2445/218093 |