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| Item Type: | Article |
|---|---|
| Title: | Genomic inversions and GOLGA core duplicons underlie disease instability at the 15q25 locus |
| Creators Name: | Maggiolini, F.A.M., Cantsilieris, S., D'Addabbo, P., Manganelli, M., Coe, B.P., Dumont, B.L., Sanders, A.D., Pang, A.W.C., Vollger, M.R., Palumbo, O., Palumbo, P., Accadia, M., Carella, M., Eichler, E.E. and Antonacci, F. |
| Abstract: | Human chromosome 15q25 is involved in several disease-associated structural rearrangements, including microdeletions and chromosomal markers with inverted duplications. Using comparative fluorescence in situ hybridization, strand-sequencing, single-molecule, real-time sequencing and Bionano optical mapping analyses, we investigated the organization of the 15q25 region in human and nonhuman primates. We found that two independent inversions occurred in this region after the fission event that gave rise to phylogenetic chromosomes XIV and XV in humans and great apes. One of these inversions is still polymorphic in the human population today and may confer differential susceptibility to 15q25 microdeletions and inverted duplications. The inversion breakpoints map within segmental duplications containing core duplicons of the GOLGA gene family and correspond to the site of an ancestral centromere, which became inactivated about 25 million years ago. The inactivation of this centromere likely released segmental duplications from recombination repression typical of centromeric regions. We hypothesize that this increased the frequency of ectopic recombination creating a hotspot of hominid inversions where dispersed GOLGA core elements now predispose this region to recurrent genomic rearrangements associated with disease. |
| Keywords: | Autoantigens, Chromosomal Instability, Chromosome Inversion, Gene Dosage, Gene Rearrangement, Genetic Recombination, Genomic Segmental Duplications, Golgi Matrix Proteins, Hominidae, Pair 15 Human Chromosomes, Phylogeny, Primates, Molecular Evolution, Multigene Family, Species Specificity, Animals |
| Source: | PLoS Genetics |
| ISSN: | 1553-7404 |
| Publisher: | Public Library of Science |
| Volume: | 15 |
| Number: | 3 |
| Page Range: | e1008075 |
| Date: | 27 March 2019 |
| Official Publication: | https://doi.org/10.1371/journal.pgen.1008075 |
| PubMed: | View item in PubMed |
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