Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability
Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into its instability, we sequenced the region in patients, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromos...
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| Format: | Online |
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2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244265/ |
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pubmed-4244265 |
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pubmed-42442652015-06-01 Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability Antonacci, Francesca Dennis, Megan Y. Huddleston, John Sudmant, Peter H. Steinberg, Karyn Meltz Rosenfeld, Jill A. Miroballo, Mattia Graves, Tina A. Vives, Laura Malig, Maika Denman, Laura Raja, Archana Stuart, Andrew Tang, Joyce Munson, Brenton Shaffer, Lisa G. Amemiya, Chris T. Wilson, Richard K. Eichler, Evan E. Article Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into its instability, we sequenced the region in patients, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mbp. These configurations arose recently (~0.5–0.9 million years ago) as a result of human-specific expansions of segmental duplications and two independent inversion events. All inversion breakpoints map near GOLGA8 core duplicons—a ~14 kbp primate-specific chromosome 15 repeat that became organized into larger palindromic structures. GOLGA8-flanked palindromes also demarcate the breakpoints of recurrent 15q13.3 microdeletions, the expansion of chromosome 15 segmental duplications in the human lineage, and independent structural changes in apes. The significant clustering (p=0.002) of breakpoints provides mechanistic evidence for the role of this core duplicon and its palindromic architecture in promoting evolutionary and disease-related instability of chromosome 15. 2014-10-19 2014-12 /pmc/articles/PMC4244265/ /pubmed/25326701 http://dx.doi.org/10.1038/ng.3120 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Antonacci, Francesca Dennis, Megan Y. Huddleston, John Sudmant, Peter H. Steinberg, Karyn Meltz Rosenfeld, Jill A. Miroballo, Mattia Graves, Tina A. Vives, Laura Malig, Maika Denman, Laura Raja, Archana Stuart, Andrew Tang, Joyce Munson, Brenton Shaffer, Lisa G. Amemiya, Chris T. Wilson, Richard K. Eichler, Evan E. |
| spellingShingle |
Antonacci, Francesca Dennis, Megan Y. Huddleston, John Sudmant, Peter H. Steinberg, Karyn Meltz Rosenfeld, Jill A. Miroballo, Mattia Graves, Tina A. Vives, Laura Malig, Maika Denman, Laura Raja, Archana Stuart, Andrew Tang, Joyce Munson, Brenton Shaffer, Lisa G. Amemiya, Chris T. Wilson, Richard K. Eichler, Evan E. Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| author_facet |
Antonacci, Francesca Dennis, Megan Y. Huddleston, John Sudmant, Peter H. Steinberg, Karyn Meltz Rosenfeld, Jill A. Miroballo, Mattia Graves, Tina A. Vives, Laura Malig, Maika Denman, Laura Raja, Archana Stuart, Andrew Tang, Joyce Munson, Brenton Shaffer, Lisa G. Amemiya, Chris T. Wilson, Richard K. Eichler, Evan E. |
| author_sort |
Antonacci, Francesca |
| title |
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| title_short |
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| title_full |
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| title_fullStr |
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| title_full_unstemmed |
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| title_sort |
palindromic golga8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability |
| description |
Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into its instability, we sequenced the region in patients, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mbp. These configurations arose recently (~0.5–0.9 million years ago) as a result of human-specific expansions of segmental duplications and two independent inversion events. All inversion breakpoints map near GOLGA8 core duplicons—a ~14 kbp primate-specific chromosome 15 repeat that became organized into larger palindromic structures. GOLGA8-flanked palindromes also demarcate the breakpoints of recurrent 15q13.3 microdeletions, the expansion of chromosome 15 segmental duplications in the human lineage, and independent structural changes in apes. The significant clustering (p=0.002) of breakpoints provides mechanistic evidence for the role of this core duplicon and its palindromic architecture in promoting evolutionary and disease-related instability of chromosome 15. |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244265/ |
| _version_ |
1613160847469707264 |