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

CNVRs chr1:109,367,944–109,371,874(a) and chr2:39,733,850–39,748,858 (b) enriched in diabetes cases. Red rectangles represent deletions in cases and controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: CNVRs chr1:109,367,944–109,371,874(a) and chr2:39,733,850–39,748,858 (b) enriched in diabetes cases. Red rectangles represent deletions in cases and controls.

Mentions: Among the nominally significant loci, there are 16 regions that overlap with gene exons (Table 3) which are very likely to have direct impact on the gene products. Taking into account of upfront SNP QC for CNV analysis and SNP collapsing into CNVR, we defined the experiment-wide significance level of P < 5 × 10−4 (Methods). Among the 16 regions, CNVR chr1:109367944-109371874 reached the such significance level and with only 1 control sample containing a deletion in this region (Table 3 and Fig. 2a). This region overlaps with one exon and two introns of the gene AKNA Domain Containing 1 (AKNAD1, C1orf62), containing an AKNA domain which is present in AT-hook-containing transcription factors. Another CNVR of P < 5 × 10−4 is located at chr2:39733850-39748858 (Table 3 and Fig. 2b). Both these CNVRs are deletions.


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)

CNVRs chr1:109,367,944–109,371,874(a) and chr2:39,733,850–39,748,858 (b) enriched in diabetes cases. Red rectangles represent deletions in cases and controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: CNVRs chr1:109,367,944–109,371,874(a) and chr2:39,733,850–39,748,858 (b) enriched in diabetes cases. Red rectangles represent deletions in cases and controls.
Mentions: Among the nominally significant loci, there are 16 regions that overlap with gene exons (Table 3) which are very likely to have direct impact on the gene products. Taking into account of upfront SNP QC for CNV analysis and SNP collapsing into CNVR, we defined the experiment-wide significance level of P < 5 × 10−4 (Methods). Among the 16 regions, CNVR chr1:109367944-109371874 reached the such significance level and with only 1 control sample containing a deletion in this region (Table 3 and Fig. 2a). This region overlaps with one exon and two introns of the gene AKNA Domain Containing 1 (AKNAD1, C1orf62), containing an AKNA domain which is present in AT-hook-containing transcription factors. Another CNVR of P < 5 × 10−4 is located at chr2:39733850-39748858 (Table 3 and Fig. 2b). Both these CNVRs are deletions.

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