A comprehensive profile of DNA copy number variations in a Korean population: identification of copy number invariant regions among Koreans

Jeon, Jae‐Pil; Shim, Sung Mi; Jung, Jongsun; Nam, Hyun-Yeol; Lee, Hye Jin; Oh, Bermseok; Kimm, Kuchan; Kim, Hyung Lae; Han, Bok Ghee

doi:10.3858/emm.2009.41.9.068

Cited by 9 publications

(8 citation statements)

References 40 publications

(36 reference statements)

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“…The QMPSF reaction included the Factor VIII gene and CN2-2 as references [34,36,37]. The relative copy numbers of a target locus were calculated in relation to the copy numbers of the Factor VIII gene or CN2-2.…”

Section: Methodsmentioning

confidence: 99%

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

et al. 2010

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BackgroundRecent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of LEPR gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the LEPR gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the LEPR gene locus in DNA copy number analyses.ResultsWe identified DNA copy number variations at the LEPR gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between LEPR and LEPROT genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (p = 1.24 × 10-7) and women (p = 9.45 × 10-5), as well as higher total cholesterol levels in men (p = 9.96 × 10-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.ConclusionsThis work suggests that a structural variation at the LEPR gene locus is functionally associated with complex metabolic traits and the risk of T2DM.

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Section: Methodsmentioning

confidence: 99%

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

et al. 2010

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“…A number of approaches have been used to detect the presence of CNV. The main platforms are comparative genomic hybridisation (CGH) arrays [ 29 – 33 ], SNP arrays [ 34 – 37 ] and depth of coverage metrics applied to whole genome sequence data (e.g., [ 38 – 42 ]). Further, there are a variety of algorithms that can be used to analyse available resultant data.…”

Section: Introductionmentioning

confidence: 99%

Copy number variants in the sheep genome detected using multiple approaches

Jenkins¹,

Goddard²,

Black

et al. 2016

BMC Genomics

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BackgroundCopy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs.ResultsIn total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %).ConclusionsThis study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2754-7) contains supplementary material, which is available to authorized users.

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“…A number of approaches have been used to detect the presence of CNV. The main platforms are comparative genomic hybridisation (CGH) arrays [29-33], SNP arrays [34-37] and depth of coverage metrics applied to whole genome sequence data (e.g., [38-42]). Further, there are a variety of algorithms that can be used to analyse available resultant data.…”

Section: Introductionmentioning

confidence: 99%

Copy number variants in the sheep genome detected using multiple approaches

Jenkins¹,

Goddard²,

Black

et al. 2016

Preprint

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Background: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. Results: In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). Conclusions: This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.

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A comprehensive profile of DNA copy number variations in a Korean population: identification of copy number invariant regions among Koreans

Cited by 9 publications

References 40 publications

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

Copy number variants in the sheep genome detected using multiple approaches

Copy number variants in the sheep genome detected using multiple approaches

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