KGVDB: a population-based genomic map of CNVs tagged by SNPs in Koreans

Moon, Sanghoon; Jung, Kwang Su; Kim, Young Jin; Hwang, Mi Yeong; Han, Kyungsook; Lee, Jong‐Young; Park, Kiejung; Kim, Bong-Jo

doi:10.1093/bioinformatics/btt173

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…In recent years, each of genotyping arrays, array-CGH microarrays, and next-generation sequencing have all been implemented successfully to detect structural variation in human cohorts (reviewed in [ 45 ]). While the majority of studies continue with HapMap cohorts, there has been a recent increase in the number of reports from non-HapMap populations, the majority of which are still ancestrally similar to pre-existing HapMap populations (e.g., East Asian populations) [ 51 – 53 ]. To date, however, there has been no systematic characterization of CNVs in Gulf Arabs, a population witnessing a growth in clinical genomics testing but whose ancestry is not adequately represented in current HapMap and 1000 Genomes populations.…”

Section: Discussionmentioning

confidence: 99%

“…As detection methods continue to improve, so will the discovery of new genes and loci whose deletion or duplication could lead to morbid clinical phenotypes in specific populations. This kind of population specificity will have detrimental effects on the design of population-specific clinical CHG-arrays, and on the interpretation and assignment of pathogenicity of CNV findings in individuals from different ethnic populations [ 25 , 51 – 54 ]. This issue is of special relevance to Arabs in general and Qataris specifically, for whom there is a paucity of databases of CNVs observed in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

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Copy number variations in the genome of the Qatari population

et al. 2015

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BackgroundThe populations of the Arabian Peninsula remain the least represented in public genetic databases, both in terms of single nucleotide variants and of larger genomic mutations. We present the first high-resolution copy number variation (CNV) map for a Gulf Arab population, using a hybrid approach that integrates array genotyping intensity data and next-generation sequencing reads to call CNVs in the Qatari population.MethodsCNVs were detected in 97 unrelated Qatari individuals by running two calling algorithms on each of two primary datasets: high-resolution genotyping (Illumina Omni 2.5M) and high depth whole-genome sequencing (Illumina PE 100bp). The four call-sets were integrated to identify high confidence CNV regions, which were subsequently annotated for putative functional effect and compared to public databases of CNVs in other populations. The availability of genome sequence was leveraged to identify tagging SNPs in high LD with common deletions in this population, enabling their imputation from genotyping experiments in the future.ResultsGenotyping intensities and genome sequencing data from 97 Qataris were analyzed with four different algorithms and integrated to discover 16,660 high confidence CNV regions (CNVRs) in the total population, affecting ~28 Mb in the median Qatari genome. Up to 40 % of all CNVs affected genes, including novel CNVs affecting Mendelian disease genes, segregating at different frequencies in the 3 major Qatari subpopulations, including those with Bedouin, Persian/South Asian, and African ancestry. Consistent with high consanguinity levels in the Bedouin subpopulation, we found an increased burden for homozygous deletions in this group. In comparison to known CNVs in the comprehensive Database of Genomic Variants, we found that 5 % of all CNVRs in Qataris were completely novel, with an enrichment of CNVs affecting several known chromosomal disorder loci and genes known to regulate sugar metabolism and type 2 diabetes in the Qatari cohort. Finally, we leveraged the availability of genome sequence to find suitable tagging SNPs for common deletions in this population.ConclusionWe combine four independently generated datasets from 97 individuals to study CNVs for the first time at high-resolution in a Gulf Arab population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1991-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Copy number variations in the genome of the Qatari population

et al. 2015

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“…We first used the 3,601 CNVRs from the previous Korean CNV study using 4,694 individuals 20 . These were part of 8,842 Korea Association Resource (KARE) Project genome-wide association study (GWAS) subjects who satisfied quality control criteria, including exclusion of any kind of cancer samples (n = 101) from 10,038 subjects (Figure S1A) 21 …”

Section: Methodsmentioning

confidence: 99%

Programmable Nuclease-Based Integration into Novel Extragenic Genomic Safe Harbor Identified from Korean Population-Based CNV Analysis

Lee

Moon

Abu-Bonsrah

et al. 2019

Molecular Therapy - Oncolytics

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Here, we found two genomic safe harbor (GSH) candidates from chromosomes 3 and 8, based on large-scale population-based cohort data from 4,694 Koreans by CNV analysis. Furthermore, estimated genotype of these CNVRs was validated by quantitative real-time PCR, and epidemiological data examined no significant genetic association between diseases or traits and two CNVRs. After screening the GSH candidates by in silico approaches, we designed TALEN pairs to integrate EGFP expression cassette into human cell lines in order to confirm the functionality of GSH candidates in an in vitro setting. As a result, transgene insertion into one of the two loci using TALEN showed robust transgene expression comparable to that with an AAVS1 site without significantly perturbing neighboring genes. Changing the promoter or cell type did not noticeably disturb this trend. Thus, we could validate two CNVRs as a site for effective and safe transgene insertion in human cells.

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“…To investigate CNV-miRNAs in the Korean population, CNV regions from our previously reported CNV study were analyzed (22). Briefly, 4,694 samples that are part of the Korean Genome Epidemiology Study were genotyped with the NimbleGen HD2 3x720 K comparative genomic hybridization array.…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, our previously reported CNV data that were obtained from population-based genome-wide approaches (22) was analyzed and candidate CNV-miRNAs with biological functions were identified. Additionally, the roles of miR-650 in the production of IL6, which is induced by IL1B in human MG-63 osteosarcoma cells, were investigated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-650 in a copy number-variable region regulates the production of interleukin 6 in human osteosarcoma cells

et al. 2015

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Abstract. Copy number variation is a well-known genetic variation. microRNAs (miRNAs/miRs) are non-coding RNAs that mediate gene expression by regulating target mRNAs. In the present study, copy number deletions encompassing miRNA coding regions were investigated to determine the association between the deletion of miRNA and its phenotypic effects. A total of 38 human miRNAs in copy number variants were identified and miR-650, which is functional in the human osteosarcoma MG-63 cell line, was selected. Overexpression of miR-650 decreased the expression of inhibitor of growth family member 4 (ING4) in the MG-63 cells and increased interleukin (IL)6 transcription, as well as IL6 secretion in IL1B-stimulated cells. Furthermore, miR-650 downregulated the amount of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor α and increased the transcriptional activity of nuclear factor (NF)κB. Downregulation of ING4 also increased the production of IL6, similar to miR-650 overexpression. Taken together, these data indicate that miR-650 plays a significant role in the production of IL6 by regulating ING4 expression and NFκB signaling in IL1B-stimulated MG-63 osteosarcoma

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KGVDB: a population-based genomic map of CNVs tagged by SNPs in Koreans

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 9 publications

References 14 publications

Copy number variations in the genome of the Qatari population

Copy number variations in the genome of the Qatari population

Programmable Nuclease-Based Integration into Novel Extragenic Genomic Safe Harbor Identified from Korean Population-Based CNV Analysis

MicroRNA-650 in a copy number-variable region regulates the production of interleukin 6 in human osteosarcoma cells

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