@article{cd8b373341dd4544bbd22d053551cae7,
title = "Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability",
abstract = "Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into the instability of this region, we sequenced it in affected individuals, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mb. These configurations arose recently ({\^a} 1/40.5-0.9 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 {\^a} 1/414-kb 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 the evolutionary and disease-related instability of chromosome 15.",
author = "Francesca Antonacci and Dennis, {Megan Y.} and John Huddleston and Sudmant, {Peter H.} and Steinberg, {Karyn Meltz} and Rosenfeld, {Jill A.} and Mattia Miroballo and Graves, {Tina A.} and Laura Vives and Maika Malig and Laura Denman and Archana Raja and Andrew Stuart and Joyce Tang and Brenton Munson and Shaffer, {Lisa G.} and Amemiya, {Chris T.} and Wilson, {Richard K.} and Eichler, {Evan E.}",
note = "Funding Information: We thank M. Ventura, C. Campbell and H.C. Mefford for useful discussions and T. Brown for critical review of the manuscript. We also thank S. Diede, H. Tanaka, B. Brewer, C. Payen, L. Harshman and K. Penewit for experimental advice and support for the palindromic snapback assay. We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren and E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. This work was supported, in part, by US National Institutes of Health grants HG002385 and HG004120 to E.E.E. M.Y.D. is supported by the National Institute of Neurological Disorder and Stroke of the US National Institutes of Health (award K99NS083627). E.E.E. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2014 Nature America, Inc. All rights reserved.",
year = "2014",
month = dec,
day = "11",
doi = "10.1038/ng.3120",
language = "English",
volume = "46",
pages = "1293--1302",
journal = "Nature Genetics",
issn = "1061-4036",
number = "12",
}