Limits...
CNV Analysis Associates AKNAD1 with Type-2 Diabetes in Jordan Subpopulations.

Dajani R, Li J, Wei Z, Glessner JT, Chang X, Cardinale CJ, Pellegrino R, Wang T, Hakooz N, Khader Y, Sheshani A, Zandaki D, Hakonarson H - Sci Rep (2015)

Bottom Line: We found a CNV region in protein tyrosine phosphatase receptor type D (PTPRD) with significant association with T2D.Endoplasmic reticulum (ER)-related pathways were significantly enriched among genes which are predicted to be functionally associated with human or mouse homologues of AKNAD1.We identified and experimentally validated a significant CNVR in gene AKNAD1 associated with T2D.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan.

ABSTRACT
Previous studies have identified a number of single nucleotide polymorphisms (SNPs) associated with type-2 diabetes (T2D), but copy number variation (CNV) association has rarely been addressed, especially in populations from Jordan. To investigate CNV associations for T2D in populations in Jordan, we conducted a CNV analysis based on intensity data from genome-wide SNP array, including 34 T2D cases and 110 healthy controls of Chechen ethnicity, as well as 34 T2D cases and 106 healthy controls of Circassian ethnicity. We found a CNV region in protein tyrosine phosphatase receptor type D (PTPRD) with significant association with T2D. PTPRD has been reported to be associated with T2D in genome-wide association studies (GWAS). We additionally identified 16 CNV regions associated with T2D which overlapped with gene exons. Of particular interest, a CNV region in the gene AKNA Domain Containing 1 (AKNAD1) surpassed the experiment-wide significance threshold. Endoplasmic reticulum (ER)-related pathways were significantly enriched among genes which are predicted to be functionally associated with human or mouse homologues of AKNAD1. This is the first CNV analysis of a complex disease in populations of Jordan. We identified and experimentally validated a significant CNVR in gene AKNAD1 associated with T2D.

No MeSH data available.


Related in: MedlinePlus

qPCR validation of CNVR chr1:109,367,944–109,371,874.Two independent probes were used, results of which are shown in (a) and (b) respectively. Copy number (CN) was calculated from triplicate runs per probe for each sample by using CopyCaller (Applied Biosystems). The copy number range bars indicate the minimal and maximal copy number calculated for each sample. Diabetic samples carrying the CNVR detected by SNP array are shown in light-blue in (a) or light-green in (b). Other samples with CN = 2 at this locus were randomly selected from our cohort, which are represented by dark-blue in (a) or dark-green in (b). The last sample of CN = 2 in each panel represents a sample of mixed human genomic DNA from Promega.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4543987&req=5

f3: qPCR validation of CNVR chr1:109,367,944–109,371,874.Two independent probes were used, results of which are shown in (a) and (b) respectively. Copy number (CN) was calculated from triplicate runs per probe for each sample by using CopyCaller (Applied Biosystems). The copy number range bars indicate the minimal and maximal copy number calculated for each sample. Diabetic samples carrying the CNVR detected by SNP array are shown in light-blue in (a) or light-green in (b). Other samples with CN = 2 at this locus were randomly selected from our cohort, which are represented by dark-blue in (a) or dark-green in (b). The last sample of CN = 2 in each panel represents a sample of mixed human genomic DNA from Promega.

Mentions: We further tested the top CNVR of chr1:109367944-109371874 with quantitative polymerase chain reaction (qPCR) an independent experimental assay (Fig. 3). All diabetic samples carrying a CNV at this locus except one sample that was unavailable for analysis were included in the experiment. Eight randomly selected samples without CNVs detected on the array were used as copy number controls (CN = 2). A sample of mixed human genomic DNA from Promega was also included as a control. Our qPCR experiment yielded consistent results to those detected on the Illumina array.


CNV Analysis Associates AKNAD1 with Type-2 Diabetes in Jordan Subpopulations.

Dajani R, Li J, Wei Z, Glessner JT, Chang X, Cardinale CJ, Pellegrino R, Wang T, Hakooz N, Khader Y, Sheshani A, Zandaki D, Hakonarson H - Sci Rep (2015)

qPCR validation of CNVR chr1:109,367,944–109,371,874.Two independent probes were used, results of which are shown in (a) and (b) respectively. Copy number (CN) was calculated from triplicate runs per probe for each sample by using CopyCaller (Applied Biosystems). The copy number range bars indicate the minimal and maximal copy number calculated for each sample. Diabetic samples carrying the CNVR detected by SNP array are shown in light-blue in (a) or light-green in (b). Other samples with CN = 2 at this locus were randomly selected from our cohort, which are represented by dark-blue in (a) or dark-green in (b). The last sample of CN = 2 in each panel represents a sample of mixed human genomic DNA from Promega.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543987&req=5

f3: qPCR validation of CNVR chr1:109,367,944–109,371,874.Two independent probes were used, results of which are shown in (a) and (b) respectively. Copy number (CN) was calculated from triplicate runs per probe for each sample by using CopyCaller (Applied Biosystems). The copy number range bars indicate the minimal and maximal copy number calculated for each sample. Diabetic samples carrying the CNVR detected by SNP array are shown in light-blue in (a) or light-green in (b). Other samples with CN = 2 at this locus were randomly selected from our cohort, which are represented by dark-blue in (a) or dark-green in (b). The last sample of CN = 2 in each panel represents a sample of mixed human genomic DNA from Promega.
Mentions: We further tested the top CNVR of chr1:109367944-109371874 with quantitative polymerase chain reaction (qPCR) an independent experimental assay (Fig. 3). All diabetic samples carrying a CNV at this locus except one sample that was unavailable for analysis were included in the experiment. Eight randomly selected samples without CNVs detected on the array were used as copy number controls (CN = 2). A sample of mixed human genomic DNA from Promega was also included as a control. Our qPCR experiment yielded consistent results to those detected on the Illumina array.

Bottom Line: We found a CNV region in protein tyrosine phosphatase receptor type D (PTPRD) with significant association with T2D.Endoplasmic reticulum (ER)-related pathways were significantly enriched among genes which are predicted to be functionally associated with human or mouse homologues of AKNAD1.We identified and experimentally validated a significant CNVR in gene AKNAD1 associated with T2D.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan.

ABSTRACT
Previous studies have identified a number of single nucleotide polymorphisms (SNPs) associated with type-2 diabetes (T2D), but copy number variation (CNV) association has rarely been addressed, especially in populations from Jordan. To investigate CNV associations for T2D in populations in Jordan, we conducted a CNV analysis based on intensity data from genome-wide SNP array, including 34 T2D cases and 110 healthy controls of Chechen ethnicity, as well as 34 T2D cases and 106 healthy controls of Circassian ethnicity. We found a CNV region in protein tyrosine phosphatase receptor type D (PTPRD) with significant association with T2D. PTPRD has been reported to be associated with T2D in genome-wide association studies (GWAS). We additionally identified 16 CNV regions associated with T2D which overlapped with gene exons. Of particular interest, a CNV region in the gene AKNA Domain Containing 1 (AKNAD1) surpassed the experiment-wide significance threshold. Endoplasmic reticulum (ER)-related pathways were significantly enriched among genes which are predicted to be functionally associated with human or mouse homologues of AKNAD1. This is the first CNV analysis of a complex disease in populations of Jordan. We identified and experimentally validated a significant CNVR in gene AKNAD1 associated with T2D.

No MeSH data available.


Related in: MedlinePlus