Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes

Grochowski, C. M., Gu, S., Yuan, B., Tcw, J., Brennand, K. J., Sebat, J., Malhotra, D., McCarthy, S., Rudolph, U., Lindstrand, A., Chong, Z., Levy, D. L., Lupski, J. R., Carvalho, C. M. B. (April 2018) Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes. Hum Mutat. ISSN 1059-7794

URL: https://www.ncbi.nlm.nih.gov/pubmed/29696747
DOI: 10.1002/humu.23537

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 3 duplications and 3 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. This article is protected by copyright. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: Chromosomal abnormalities Marker chromosome Microarrays Psychiatric genetics SNP analysis Structural variation
Subjects: bioinformatics
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > SNP
CSHL Authors:
Communities: CSHL labs > McCombie lab
Depositing User: Matt Covey
Date: 25 April 2018
Date Deposited: 23 May 2018 14:07
Last Modified: 23 May 2018 14:07
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36561

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