@article{e519bf2bfc664d3fb3fdee63e7a49243,
title = "Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes",
abstract = "Small supernumerary marker chromosomes (sSMC) are chromosomal fragments difficult to characterize genomically. Here, we detail a proband with schizoaffective disorder and a mother with bipolar disorder with psychotic features who present with a marker chromosome that segregates with disease. We explored the architecture of this marker and investigated its temporal origin. Array comparative genomic hybridization (aCGH) analysis revealed three duplications and three triplications that spanned the short arm of chromosome 9, suggestive of a chromoanasynthesis-like event. Segregation of marker genotypes, phased using sSMC mosaicism in the mother, provided evidence that it was generated during a germline-level event in the proband's maternal grandmother. Whole-genome sequencing (WGS) was performed to resolve the structure and junctions of the chromosomal fragments, revealing further complexities. While structural variations have been previously associated with neuropsychiatric disorders and marker chromosomes, here we detail the precise architecture, human life-cycle genesis, and propose a DNA replicative/repair mechanism underlying formation.",
keywords = "SNP analysis, chromosomal abnormalities, marker chromosome, microarrays, psychiatric genetics, structural variation",
author = "Grochowski, {Christopher M.} and Shen Gu and Bo Yuan and Julia Tcw and Brennand, {Kristen J.} and Jonathan Sebat and Dheeraj Malhotra and Shane McCarthy and Uwe Rudolph and Anna Lindstrand and Zechen Chong and Levy, {Deborah L.} and Lupski, {James R.} and Carvalho, {Claudia M.B.}",
note = "Funding Information: We would like to thank the patients and their families who generously provided their time and genetic material. We would also like to acknowledge Jesper Eisfeldt who assisted with the initial WGS analysis and file transfer. J.R.L. holds stock ownership in 23andMe Inc. and Lasergen Inc., is a paid consultant for Regeneron Pharmaceuticals, and is a coinventor on multiple United States and European patents related to molecular diagnostics. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from molecular genetic testing offered in the Baylor Medical Genetics Laboratories (BMGL). J.R.L. is on the Scientific Advisory Board of the BMGL. Funding Information: Contract grant sponsors: National Insti tute of Neurological Disorders and Stroke (R35 NS105078); National Human Genome Research/National Heart Lung and Blood Institute (NHGRI/NHLBI) (UM1 HG006542); National Institute of Health/National Institute of General Medical Sciences (NIH/NIGMS) (R01 GM106373-04, R01MH071523); Anonymous Foundation; Ellison Foundation; Team Daniel; Carmela and Menachem Abraham Fund; NIH (MH076431, R21MH104505, R01 MH101454, R21MH105732, R21MH097470); Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2018",
month = jul,
doi = "10.1002/humu.23537",
language = "English (US)",
volume = "39",
pages = "939--946",
journal = "Human mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "7",
}