title: A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease.
abstract: Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. Although the RET proto-oncogene is considered to be the main risk factor for HSCR, only about 30% of the HSCR cases can be explained by variations in previously known genes including RET. Recently, copy number variation (CNV) and loss of heterozygosity (LOH) have emerged as new ways to understand human genomic variation. The goal of this present study is to identify new HSCR genetic factors related to CNV in Korean patients. In the genome-wide genotyping, using Illumina's HumanOmni1-Quad BeadChip (1,140,419 markers), of 123 HSCR patients and 432 unaffected subjects (total n = 555), a total of 8,188 CNVs (1 kb ∼ 1 mb) were identified by CNVpartition. As a result, 16 CNV regions and 13 LOH regions were identified as associated with HSCR (minimum P = 0.0005). Two top CNV regions (deletions at chr6:32675155-32680480 and chr22:20733495-21607293) were successfully validated by additional real-time quantitative polymerase chain reaction analysis. In addition, 2 CNV regions (6p21.32 and 22q11.21) and 2 LOH regions (3p22.2 and 14q23.3) were discovered to be unique to the HSCR patients group. Regarding the large-scale chromosomal aberrations (>1 mb), 11 large aberrations in the HSCR patients group were identified, which suggests that they may be a risk factor for HSCR. Although further replication in a larger cohort is needed, our findings may contribute to the understanding of the etiology of HSCR.
authors.affiliation: Laboratory of Translational Genomics, Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Physiology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: InSong
authors.initials: I
authors.lastname: Koh
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Republic of Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jeong-Meen
authors.initials: JM
authors.lastname: Seo
authors.affiliation: Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae-Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Pediatric Surgery, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Tak
authors.initials: JT
authors.lastname: Oh
authors.affiliation: Department of Pediatric Surgery, Seoul National University Children's Hospital, Seoul, Republic of Korea.
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Surgery, Jeju National University Hospital, Aran 13gil 15, Jeju, Republic of Korea.
authors.forename: Kyuwhan
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Calif, USA; Semel Center for Informatics and Personalized Genomics, University of California, Los Angeles, Calif, USA.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Sul
authors.affiliation: Laboratory of Translational Genomics, Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea. Electronic address: soykm@sogang.ac.kr.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea; Department of Life Science, Sogang University, Seoul, Republic of Korea. Electronic address: hdshin@sogang.ac.kr.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D000090063:Proto-Oncogene Mas; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D055815:Young Adult