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Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus
The impact of segmental duplications on human evolution and disease is only just starting to unfold, thanks to advancements in sequencing technologies that allow for their discovery and precise genotyping. The 15q11-q13 locus is a hotspot of recurrent copy number variation associated with Prader–Wil...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648317/ https://www.ncbi.nlm.nih.gov/pubmed/37958807 http://dx.doi.org/10.3390/ijms242115818 |
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author | Paparella, Annalisa L’Abbate, Alberto Palmisano, Donato Chirico, Gerardina Porubsky, David Catacchio, Claudia R. Ventura, Mario Eichler, Evan E. Maggiolini, Flavia A. M. Antonacci, Francesca |
author_facet | Paparella, Annalisa L’Abbate, Alberto Palmisano, Donato Chirico, Gerardina Porubsky, David Catacchio, Claudia R. Ventura, Mario Eichler, Evan E. Maggiolini, Flavia A. M. Antonacci, Francesca |
author_sort | Paparella, Annalisa |
collection | PubMed |
description | The impact of segmental duplications on human evolution and disease is only just starting to unfold, thanks to advancements in sequencing technologies that allow for their discovery and precise genotyping. The 15q11-q13 locus is a hotspot of recurrent copy number variation associated with Prader–Willi/Angelman syndromes, developmental delay, autism, and epilepsy and is mediated by complex segmental duplications, many of which arose recently during evolution. To gain insight into the instability of this region, we characterized its architecture in human and nonhuman primates, reconstructing the evolutionary history of five different inversions that rearranged the region in different species primarily by accumulation of segmental duplications. Comparative analysis of human and nonhuman primate duplication structures suggests a human-specific gain of directly oriented duplications in the regions flanking the GOLGA cores and HERC segmental duplications, representing potential genomic drivers for the human-specific expansions. The increasing complexity of segmental duplication organization over the course of evolution underlies its association with human susceptibility to recurrent disease-associated rearrangements. |
format | Online Article Text |
id | pubmed-10648317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106483172023-10-31 Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus Paparella, Annalisa L’Abbate, Alberto Palmisano, Donato Chirico, Gerardina Porubsky, David Catacchio, Claudia R. Ventura, Mario Eichler, Evan E. Maggiolini, Flavia A. M. Antonacci, Francesca Int J Mol Sci Article The impact of segmental duplications on human evolution and disease is only just starting to unfold, thanks to advancements in sequencing technologies that allow for their discovery and precise genotyping. The 15q11-q13 locus is a hotspot of recurrent copy number variation associated with Prader–Willi/Angelman syndromes, developmental delay, autism, and epilepsy and is mediated by complex segmental duplications, many of which arose recently during evolution. To gain insight into the instability of this region, we characterized its architecture in human and nonhuman primates, reconstructing the evolutionary history of five different inversions that rearranged the region in different species primarily by accumulation of segmental duplications. Comparative analysis of human and nonhuman primate duplication structures suggests a human-specific gain of directly oriented duplications in the regions flanking the GOLGA cores and HERC segmental duplications, representing potential genomic drivers for the human-specific expansions. The increasing complexity of segmental duplication organization over the course of evolution underlies its association with human susceptibility to recurrent disease-associated rearrangements. MDPI 2023-10-31 /pmc/articles/PMC10648317/ /pubmed/37958807 http://dx.doi.org/10.3390/ijms242115818 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Paparella, Annalisa L’Abbate, Alberto Palmisano, Donato Chirico, Gerardina Porubsky, David Catacchio, Claudia R. Ventura, Mario Eichler, Evan E. Maggiolini, Flavia A. M. Antonacci, Francesca Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus |
title | Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus |
title_full | Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus |
title_fullStr | Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus |
title_full_unstemmed | Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus |
title_short | Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus |
title_sort | structural variation evolution at the 15q11-q13 disease-associated locus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648317/ https://www.ncbi.nlm.nih.gov/pubmed/37958807 http://dx.doi.org/10.3390/ijms242115818 |
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