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 ca...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)analyses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgirelated cellular component terms and various enzymatic activities in the GO biological function category.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 in dbSNP 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.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,Grant No.31771479)Science Fund for Creative Research Groups of the NSFC(Grant No.81521003)+5 种基金Projects of International Cooperation and Exchanges of NSFC(Grant No.61661146004)Municipal Planning Projects of Scientific Technology of Guangdong(Grant No.201804020083)the Science and Technology Program of Guangzhou(Grant No.201400000004)the Natural Science Foundation of Guangdong(Grant No.2015B050501006)the Team Program of Natural Science Foundation of Guangdong(Grant No.2014A030312002)the 1000 Talents Program of China。
文摘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)analyses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgirelated cellular component terms and various enzymatic activities in the GO biological function category.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 in dbSNP 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.
