The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy
Blue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cl...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Fundació Sant Joan de Déu |
| Repositorio: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p21760 |
| Acceso en línea: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21760 |
| Access Level: | acceso abierto |
| Palabra clave: | human visual pigment genes BCM opsin gene deletion gene conversion locus control region |
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The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacyWissinger BBaumann BBuena-Atienza ERavesh ZCideciyan AVStingl KAudo IMeunier IBocquet BTraboulsi EIHardcastle AJGardner JCMichaelides MBranham KERosenberg TAndreasson SDollfus HBirch DVincent ALMartorell LCatalà Mora JKellner URüther KLorenz BPreising MNManfredini EZarate YAVijzelaar RZrenner EJacobson SGKohl Shuman visual pigment genesBCMopsin gene deletiongene conversionlocus control regionBlue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cluster on Xq28. Here, we investigated the prevalence and the landscape of submicroscopic structural variants (SVs) at single-base resolution in BCM patients. We found that about one-third (n = 73) of the 213 molecularly confirmed BCM families carry an SV, most commonly deletions restricted to the OPN1LW/OPN1MW gene cluster. The structure and precise breakpoints of the SVs were resolved in all but one of the 73 families. Twenty-two families-all from the United States-showed the same SV, and we confirmed a common ancestry of this mutation. In total, 42 distinct SVs were identified, including 40 previously unreported SVs, thereby quadrupling the number of precisely mapped SVs underlying BCM. Notably, there was no "region of overlap" among these SVs. However, 90% of SVs encompass the upstream locus control region, an essential enhancer element. Its minimal functional extent based on deletion mapping in patients was refined to 358 bp. Breakpoint analyses suggest diverse mechanisms underlying SV formation as well as in one case the gene conversion-based exchange of a 142-bp deletion between opsin genes. Using parsimonious assumptions, we reconstructed the composition and copy number of the OPN1LW/OPN1MW gene cluster prior to the mutation event and found evidence that large gene arrays may be predisposed to the occurrence of SVs at this locus.NATL ACAD SCIENCES2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21760PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICAISSN: 00278424ISSNe: 10916490reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p217602026-05-27T12:37:41Z |
| dc.title.none.fl_str_mv |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| title |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| spellingShingle |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy Wissinger B human visual pigment genes BCM opsin gene deletion gene conversion locus control region |
| title_short |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| title_full |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| title_fullStr |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| title_full_unstemmed |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| title_sort |
The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy |
| dc.creator.none.fl_str_mv |
Wissinger B Baumann B Buena-Atienza E Ravesh Z Cideciyan AV Stingl K Audo I Meunier I Bocquet B Traboulsi EI Hardcastle AJ Gardner JC Michaelides M Branham KE Rosenberg T Andreasson S Dollfus H Birch D Vincent AL Martorell L Català Mora J Kellner U Rüther K Lorenz B Preising MN Manfredini E Zarate YA Vijzelaar R Zrenner E Jacobson SG Kohl S |
| author |
Wissinger B |
| author_facet |
Wissinger B Baumann B Buena-Atienza E Ravesh Z Cideciyan AV Stingl K Audo I Meunier I Bocquet B Traboulsi EI Hardcastle AJ Gardner JC Michaelides M Branham KE Rosenberg T Andreasson S Dollfus H Birch D Vincent AL Martorell L Català Mora J Kellner U Rüther K Lorenz B Preising MN Manfredini E Zarate YA Vijzelaar R Zrenner E Jacobson SG Kohl S |
| author_role |
author |
| author2 |
Baumann B Buena-Atienza E Ravesh Z Cideciyan AV Stingl K Audo I Meunier I Bocquet B Traboulsi EI Hardcastle AJ Gardner JC Michaelides M Branham KE Rosenberg T Andreasson S Dollfus H Birch D Vincent AL Martorell L Català Mora J Kellner U Rüther K Lorenz B Preising MN Manfredini E Zarate YA Vijzelaar R Zrenner E Jacobson SG Kohl S |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
human visual pigment genes BCM opsin gene deletion gene conversion locus control region |
| topic |
human visual pigment genes BCM opsin gene deletion gene conversion locus control region |
| description |
Blue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cluster on Xq28. Here, we investigated the prevalence and the landscape of submicroscopic structural variants (SVs) at single-base resolution in BCM patients. We found that about one-third (n = 73) of the 213 molecularly confirmed BCM families carry an SV, most commonly deletions restricted to the OPN1LW/OPN1MW gene cluster. The structure and precise breakpoints of the SVs were resolved in all but one of the 73 families. Twenty-two families-all from the United States-showed the same SV, and we confirmed a common ancestry of this mutation. In total, 42 distinct SVs were identified, including 40 previously unreported SVs, thereby quadrupling the number of precisely mapped SVs underlying BCM. Notably, there was no "region of overlap" among these SVs. However, 90% of SVs encompass the upstream locus control region, an essential enhancer element. Its minimal functional extent based on deletion mapping in patients was refined to 358 bp. Breakpoint analyses suggest diverse mechanisms underlying SV formation as well as in one case the gene conversion-based exchange of a 142-bp deletion between opsin genes. Using parsimonious assumptions, we reconstructed the composition and copy number of the OPN1LW/OPN1MW gene cluster prior to the mutation event and found evidence that large gene arrays may be predisposed to the occurrence of SVs at this locus. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21760 |
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https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21760 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.publisher.none.fl_str_mv |
NATL ACAD SCIENCES |
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NATL ACAD SCIENCES |
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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA ISSN: 00278424 ISSNe: 10916490 reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname:Fundació Sant Joan de Déu |
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Fundació Sant Joan de Déu |
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r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
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r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
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