The Biological Significance of Multi-copy Regions and Their Impact on Variant Discovery
- Author:
Sun JING
1
,
2
,
3
;
Zhang YANFANG
;
Wang MINHUI
;
Guan QIAN
;
Yang XIUJIA
;
Ou Xia JIN
;
Yan MINGCHEN
;
Wang CHENGRUI
;
Zhang YAN
;
Li ZHI-HAO
;
Lan CHUNHONG
;
Mao CHEN
;
Zhou HONG-WEI
;
Hao BINGTAO
;
Zhang ZHENHAI
Author Information
1. State Key Laboratory of Organ Failure Research,National Clinical Research Center for Kidney Disease,Division of Nephrology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China
2. Department of Bioinformatics,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China
3. Key Laboratory of Mental Health of the Ministry of Education,Guangdong-Hong Kong-Macao Greater B
- Keywords:
Multi-copy sequence;
Multi-copy region;
Genetic study;
Variant discovery;
High-throughput sequencing
- From:
Genomics, Proteomics & Bioinformatics
2020;18(5):516-524
- CountryChina
- Language:Chinese
-
Abstract:
Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98％of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) anal-yses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function cat-egory. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded indbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies.
