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Transl Res. 2016 Nov;177:31-40.e6. doi: 10.1016/j.trsl.2016.06.001. Epub 2016 Jun 14.

A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease.

Author information

1
Laboratory of Translational Genomics, Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
2
Department of Physiology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
3
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Republic of Korea.
4
Division of Pediatric Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
5
Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
6
Department of Pediatric Surgery, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
7
Department of Pediatric Surgery, Seoul National University Children's Hospital, Seoul, Republic of Korea.
8
Department of Surgery, Jeju National University Hospital, Aran 13gil 15, Jeju, Republic of Korea.
9
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.
10
Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea. Electronic address: soykm@sogang.ac.kr.
11
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.

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.

PMID:
27370899
DOI:
10.1016/j.trsl.2016.06.001
[Indexed for MEDLINE]

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