Somatic deletions implicated in functional diversity of brain cells of individuals with schizophrenia and unaffected controls.
While somatic DNA copy number variations (CNVs) have been identified in multiple tissues from normal people, they have not been well studied in brain tissues from individuals with psychiatric disorders. With ultrahigh depth sequencing data, we developed an integrated pipeline for calling somatic deletions using data from multiple tissues of the same individual or a single tissue type taken from multiple individuals. Using the pipelines, we identified 106 somatic deletions in DNA from prefrontal cortex (PFC) and/or cerebellum of two normal controls subjects and/or three individuals with schizophrenia. We then validated somatic deletions in 18 genic and in 1 intergenic region. Somatic deletions in BOD1 and CBX3 were reconfirmed using DNA isolated from non-pyramidal neurons and from cells in white matter using laser capture microdissection (LCM). Our results suggest that somatic deletions may affect metabolic processes and brain development in a region specific manner.
Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
Junho
J
Kim
1] Genomic Medicine Institute (GMI), Medical Research Center, Seoul National, University, Seoul 110-799, Korea [2] Psoma Therapeutics Inc., Seoul, 153-781, Korea.
Jong-Yeon
JY
Shin
1] Genomic Medicine Institute (GMI), Medical Research Center, Seoul National, University, Seoul 110-799, Korea [2] Psoma Therapeutics Inc., Seoul, 153-781, Korea [3] Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-799, Korea [4] Department of Biochemistry and Molecular Biology, Seoul National University, College of Medicine, Seoul 110-799, Korea.
Jong-Il
JI
Kim
1] Genomic Medicine Institute (GMI), Medical Research Center, Seoul National, University, Seoul 110-799, Korea [2] Psoma Therapeutics Inc., Seoul, 153-781, Korea [3] Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-799, Korea [4] Department of Biochemistry and Molecular Biology, Seoul National University, College of Medicine, Seoul 110-799, Korea [5] Macrogen Inc., Seoul 153-781, Korea.
Jeong-Sun
JS
Seo
Stanley Brain Research Laboratory, Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD 20850.
Maree J
MJ
Webster
Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
Doheon
D
Lee
Stanley Brain Research Laboratory, Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD 20850.
Sanghyeon
S
Kim
D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004171:Diploidy; D005260:Female; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion
D015415:Biomarkers; D012333:RNA, Messenger