Copy number variations in East-Asian population and their evolutionary and functional implications

Yim, Seon‐Hee; Kim, Tae Min; Hu, Hae‐Jin; Kim, Ji Eun; Kim, Bong-Jo; Lee, Jong‐Young; Han, Bok‐Ghee; Shin, Sun; Jung, Seung‐Hyun; Chung, Yeun‐Jun

doi:10.1093/hmg/ddp564

Cited by 79 publications

(79 citation statements)

References 34 publications

(50 reference statements)

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“…[1][2][3][4][5] Most of these newer studies used high-resolution methods for detecting CNVs, such as the Affymetrix SNP Array 6.0, which has a higher density of singlenucleotide polymorphism (SNP) and copy number probes than previous microarray-based methods. This has led to an improved performance of microarray-based methods to detect smaller CNVs (o50 kb).…”

Section: Introductionmentioning

confidence: 99%

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Teo

Naidoo

et al. 2011

J Hum Genet

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The abundance of copy number variants (CNVs) and regions of homozygosity (ROHs) have been well documented in previous studies. In addition, their roles in complex diseases and traits have since been increasingly appreciated. However, only a limited amount of CNV and ROH data is currently available for the Swedish population. We conducted a population-based study to detect and characterize CNVs and ROHs in 87 randomly selected healthy Swedish individuals using the Affymetrix SNP Array 6.0. More than 600 CNV loci were detected in the population using two different CNV-detection algorithms (PennCNV and Birdsuite). A total of 196 loci were consistently identified by both algorithms, suggesting their reliability. Numerous diseaseassociated and pharmacogenetics-related genes were found to be overlapping with common CNV loci such as CFHR1/R3, LCE3B/3C, UGT2B17 and GSTT1. Correlation analysis between copy number polymorphisms (CNPs) and genome-wide association studies-identified single-nucleotide polymorphisms also indicates the potential roles of several CNPs as causal variants for diseases and traits such as body mass index, Crohn's disease and multiple sclerosis. In addition, we also identified a total of 14 815 ROHs X500 kb or 2814 ROHs X1M in the Swedish individuals with an average of 170 and 32 regions detected per individual respectively. Approximately 141 Mb or 4.92% of the genome is homozygous in each individual of the Swedish population. This is the first population-based study to investigate the population characteristics of CNVs and ROHs in the Swedish population. This study found many CNV loci that warrant further investigation, and also highlighted the abundance and importance of investigating ROHs for their associations with complex diseases and traits.

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Section: Introductionmentioning

confidence: 99%

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Teo

Naidoo

et al. 2011

J Hum Genet

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“…In addition to SNPs, DNA copy number variations (CNVs) have gained considerable interest as a source of genetic diversity (16)(17)(18). CNVs account for a major proportion of human genetic variation, and several reports have suggested that CNVs play a role in susceptibility to diseases, especially autoimmune diseases (19)(20)(21)(22)(23).…”

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confidence: 99%

Genome‐Wide Copy Number Variation Analysis Identifies Deletion Variants Associated With Ankylosing Spondylitis

Jung

Yim

et al. 2014

Arthritis & Rheumatology

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Objective. To identify ankylosing spondylitis (AS)-associated copy number variations (CNVs) in Korean subjects and their synergistic roles in the development of AS.Methods. A genome-wide association study (GWAS) was performed in 309 patients with AS and 309 control subjects, using a copy number variant (CNV) microarray. AS-associated CNV regions were replicated in 2 independent sets (625 patients and 891 control subjects) by quantitative polymerase chain reaction (PCR) and deletion-typing PCR.Results. In the CNV GWAS, 227 CNV regions were shown to be significantly associated with the risk of AS. Of the candidate CNV regions, 9 were successfully replicated in the first replication analysis: 1q32.2 (HHAT), 1p34.2 (BMP8A), 2q31.2 (PRKRA), 6p21.32 (HLA-DPB1), 11q22.1 (CNTN5), 13q13.1 (EEF1DP3), 14q24.2 (RGS6), 16p13.3, and 22q11.1 (IL17RA). The 5 deletion-type CNV regions, in 1q32.2, 2q31.2, 6p21.32, 13q13.1, and 16p13.3, were associated with an increased risk of AS, and the other 4 CNV regions were protective. In the second replication analysis, 4 CNV regions in 1q32.2, 2q31.2, 6p21.32, and 16p13.3 were replicated. Among patients with CNV regions in >4 risk-increasing loci, the risk was 18.0 times higher than that in patients without any deletions (odds ratio [OR] 17.98, P ‫؍‬ 2.3 ؋ 10 ؊7 ). Among patients with CNV regions in >2 protective loci, the risk was 5.2 times lower than that in those without any deletions (OR 0.19, P ‫؍‬ 4.0 ؋ 10 ؊10 ). The additive effects of simultaneous events were shown to be dependent on the frequency of CNV regions. Through deletion-typing PCR and sequencing, the exact sizes and breakpoint sequences were defined in 4 CNV regions. The mechanism of all 3 deletions was shown to be microhomology-based nonhomologous end joining.Conclusion. The results of this study can help to identify pathogenic mechanisms of AS and can easily be applied in the development of algorithms estimating the risk of AS.Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the sacroiliac joints and spine. Nonsteroidal antiinflammatory drugs and tumor necrosis factor ␣ (TNF␣) inhibitors are effective in controlling the signs and symptoms of active AS (1). However, it is currently unclear whether these drugs can inhibit the progress of bony ankylosis (2). Therefore, there is a great need for further research on the etiology and pathophysiology of the disease, which will help in the development of better therapies.

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“…After in vitro serum-free cell culture, the defective genes could be repaired by homologous genetic recombination, since the genomic DNAs of the two persons are considerably similar, although there are deletions, insertions, rearrangements, loss-of-function variants, and copy number variations (CNV) (Fujimoto et al, 2010;Levy et al, 2007;H. Park et al, 2010;The 1000Genomes Consortium, 2010, 2011Yim et al, 2010).…”

Section: A Possible Approach For Gene Therapy Of Some Genetic Diseasesmentioning

confidence: 99%

Gene Therapy of Some Genetic Diseases by Transferring Normal Human Genomic DNA into Somatic Cells and Stem Cells from Patients

Song¹

2011

Non-Viral Gene Therapy

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Copy number variations in East-Asian population and their evolutionary and functional implications

Cited by 79 publications

References 34 publications

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Genome‐Wide Copy Number Variation Analysis Identifies Deletion Variants Associated With Ankylosing Spondylitis

Gene Therapy of Some Genetic Diseases by Transferring Normal Human Genomic DNA into Somatic Cells and Stem Cells from Patients

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