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Sci Rep. 2017 Aug 29;7(1):9810. doi: 10.1038/s41598-017-09247-5.

Prevalence of Rare Genetic Variations and Their Implications in NGS-data Interpretation.

Author information

1
Syntekabio Incorporated, Techno-2ro B-512, Yuseong-gu, Daejeon, 34025, Republic of Korea.
2
DFTBA, CALS, Chonnam National University, Gwangju, 61186, Republic of Korea.
3
Department of Clinical Genetics, Department of Pediatrics, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
4
Department of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin-si, Gyeonggi-do, 17035, Republic of Korea.
5
Syntekabio Incorporated, Techno-2ro B-512, Yuseong-gu, Daejeon, 34025, Republic of Korea. jung@syntekabio.com.
6
Department of Clinical Genetics, Department of Pediatrics, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. jinsunglee@yuhs.ac.

Abstract

Next-generation sequencing (NGS) technology has improved enough to discover mutations associated with genetic diseases. Our study evaluated the feasibility of targeted NGS as a primary screening tool to detect causal variants and subsequently predict genetic diseases. We performed parallel computations on 3.7-megabase-targeted regions to detect disease-causing mutations in 103 participants consisting of 81 patients and 22 controls. Data analysis of the participants took about 6 hours using local databases and 200 nodes of a supercomputer. All variants in the selected genes led on average to 3.6 putative diseases for each patient while variants restricted to disease-causing genes identified the correct disease. Notably, only 12% of predicted causal variants were recorded as causal mutations in public databases: 88% had no or insufficient records. In this study, most genetic diseases were caused by rare mutations and public records were inadequate. Most rare variants, however, were not associated with genetic diseases. These data implied that novel, rare variants should not be ignored but interpreted in conjunction with additional clinical data. This step is needed so appropriate advice can be given to primary doctors and parents, thus fulfilling the purpose of this method as a primary screen for rare genetic diseases.

PMID:
28851938
PMCID:
PMC5574920
DOI:
10.1038/s41598-017-09247-5
[Indexed for MEDLINE]
Free PMC Article

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