Special Issue "Genetics of Diabetes"

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genetics and Genomics".

Deadline for manuscript submissions: closed (31 May 2015)

Special Issue Editor

Guest Editor
Dr. Claire Vandiedonck

Inserm UMR-S-958 "Genetics of diabetes", University Paris Diderot - Paris 7, School of Medicine, Site Villemin, 10 avenue de Verdun, 75010 Paris, France
Website | E-Mail
Phone: +33 157278555
Interests: immunogenetics; MHC; autoimmunity; type 1 diabetes; eQTL mapping; multifactorial genetics

Special Issue Information

Dear Colleagues,

Genetic studies, including genome-wide linkage and association studies, have been a main component of research strategies aiming at understanding the pathogenesis of various forms of diabetes. Type 1 and type 2 diabetes benefited from consortia screening large cohorts using various polymorphisms (microsatellites, SNPs and CNVs), from common to rare. For other “specific” forms of diabetes (neonatal, syndromic or atypical), characterization of homogeneous phenotypes through linkage was crucial. However, despite intensive studies, the identification of the causative variants or mutations remains challenging and the molecular mechanisms are still rarely characterized. The achievement of next-generation-sequencing technologies applied to the search for DNA variants or aiming at characterizing functional elements, as examplified by the recent ENCODE project, opens a promising era to decipher the genetic bases of diabetes, to help better understand pathogenetic mechanisms, hopefully leading to personalized medicine.
This Special Issue of “Genes” welcomes reviews and original papers covering recent genetic research on any type of diabetes, either multifactorial or monogenic, both in man and in animal models, using high-throughput omic approaches. Special interest will be given to integrative biology studies.

Dr. Claire Vandiedonck
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).

Keywords

  • diabetes
  • genetics
  • genomics
  • metagenomics
  • next-generation sequencing
  • chromatin studies
  • epigenomics
  • proteomics
  • metabolomics
  • integrative biology
  • molecular function

Published Papers (8 papers)

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Research

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Open AccessArticle Alu Elements as Novel Regulators of Gene Expression in Type 1 Diabetes Susceptibility Genes?
Genes 2015, 6(3), 577-591; doi:10.3390/genes6030577
Received: 13 April 2015 / Revised: 18 June 2015 / Accepted: 30 June 2015 / Published: 13 July 2015
PDF Full-text (542 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate
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Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate genes to identify embedded Alu elements within these genes. We observed significant enrichment of Alu elements within the T1D genes (p-value < 10e−16), which highlights their importance in T1D. Functional annotation of T1D genes harboring Alus revealed significant enrichment for immune-mediated processes (p-value < 10e−6). We also identified eight T1D genes harboring inverted Alus (IRAlus) within their 3' untranslated regions (UTRs) that are known to regulate the expression of host mRNAs by generating double stranded RNA duplexes. Our in silico analysis predicted the formation of duplex structures by IRAlus within the 3'UTRs of T1D genes. We propose that IRAlus might be involved in regulating the expression levels of the host T1D genes. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
Open AccessArticle MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise
Genes 2015, 6(2), 399-416; doi:10.3390/genes6020399
Received: 26 March 2015 / Revised: 11 June 2015 / Accepted: 18 June 2015 / Published: 23 June 2015
Cited by 3 | PDF Full-text (221 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MicroRNA (miRNA) are a class of non-coding, 19–25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic
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MicroRNA (miRNA) are a class of non-coding, 19–25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic form of diabetes; HNF1A-MODY. miR-224 is a novel miRNA in the field of diabetes. We sought to explore the role of miR-224 as a potential biomarker in diabetes, and whether such diabetes-associated-miRNA can also be detected in the urine of patients. Absolute levels of miR-224 and miR-103 were determined in the urine of n = 144 individuals including carriers of a HNF1A mutation, participants with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and normal controls. Expression levels were correlated with clinical and biochemical parameters. miR-224 was significantly elevated in the urine of carriers of a HNF1A mutation and participants with T1DM. miR-103 was highly expressed in urine across all diabetes cohorts when compared to controls. For both miR-224 and-103, we found a significant correlation between serum and urine levels (p < 0.01). We demonstrate that miRNA can be readily detected in the urine independent of clinical indices of renal dysfunction. We surmise that the differential expression levels of miR-224 in both HNF1A-MODY mutation carriers and T1DM may be an attempt to compensate for beta-cell demise. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
Open AccessArticle Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation
Genes 2013, 4(3), 485-498; doi:10.3390/genes4030485
Received: 8 June 2013 / Revised: 22 August 2013 / Accepted: 2 September 2013 / Published: 10 September 2013
Cited by 6 | PDF Full-text (186 KB) | HTML Full-text | XML Full-text
Abstract
Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS)
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Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. Objective: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. Methods: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g–2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Results: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). Conclusion: Results suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation. Full article
(This article belongs to the Special Issue Genetics of Diabetes)

Review

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Open AccessReview Genetics of Type 2 Diabetes and Clinical Utility
Genes 2015, 6(2), 372-384; doi:10.3390/genes6020372
Received: 16 April 2015 / Revised: 2 June 2015 / Accepted: 11 June 2015 / Published: 23 June 2015
Cited by 3 | PDF Full-text (107 KB) | HTML Full-text | XML Full-text
Abstract
A large proportion of heritability of type 2 diabetes (T2D) has been attributed to inherent genetics. Recent genetic studies, especially genome-wide association studies (GWAS), have identified a multitude of variants associated with T2D. It is thus reasonable to question if these findings may
[...] Read more.
A large proportion of heritability of type 2 diabetes (T2D) has been attributed to inherent genetics. Recent genetic studies, especially genome-wide association studies (GWAS), have identified a multitude of variants associated with T2D. It is thus reasonable to question if these findings may be utilized in a clinical setting. Here we briefly review the identification of risk loci for T2D and discuss recent efforts and propose future work to utilize these loci in clinical setting—for the identification of individuals who are at particularly high risks of developing T2D and for the stratification of specific health-care approaches for those who would benefit most from such interventions. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
Open AccessReview Genetics of Type 2 Diabetes—Pitfalls and Possibilities
Genes 2015, 6(1), 87-123; doi:10.3390/genes6010087
Received: 9 December 2014 / Revised: 28 January 2015 / Accepted: 27 February 2015 / Published: 12 March 2015
Cited by 24 | PDF Full-text (4249 KB) | HTML Full-text | XML Full-text
Abstract
Type 2 diabetes (T2D) is a complex disease that is caused by a complex interplay between genetic, epigenetic and environmental factors. While the major environmental factors, diet and activity level, are well known, identification of the genetic factors has been a challenge. However,
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Type 2 diabetes (T2D) is a complex disease that is caused by a complex interplay between genetic, epigenetic and environmental factors. While the major environmental factors, diet and activity level, are well known, identification of the genetic factors has been a challenge. However, recent years have seen an explosion of genetic variants in risk and protection of T2D due to the technical development that has allowed genome-wide association studies and next-generation sequencing. Today, more than 120 variants have been convincingly replicated for association with T2D and many more with diabetes-related traits. Still, these variants only explain a small proportion of the total heritability of T2D. In this review, we address the possibilities to elucidate the genetic landscape of T2D as well as discuss pitfalls with current strategies to identify the elusive unknown heritability including the possibility that our definition of diabetes and its subgroups is imprecise and thereby makes the identification of genetic causes difficult. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
Open AccessReview The Genetics of Diabetic Nephropathy
Genes 2013, 4(4), 596-619; doi:10.3390/genes4040596
Received: 18 July 2013 / Revised: 8 October 2013 / Accepted: 30 October 2013 / Published: 5 November 2013
Cited by 8 | PDF Full-text (415 KB) | HTML Full-text | XML Full-text
Abstract
Up to 40% of patients with type 1 and type 2 diabetes will develop diabetic nephropathy (DN), resulting in chronic kidney disease and potential organ failure. There is evidence for a heritable genetic susceptibility to DN, but despite intensive research efforts the causative
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Up to 40% of patients with type 1 and type 2 diabetes will develop diabetic nephropathy (DN), resulting in chronic kidney disease and potential organ failure. There is evidence for a heritable genetic susceptibility to DN, but despite intensive research efforts the causative genes remain elusive. Recently, genome-wide association studies have discovered several novel genetic variants associated with DN. The identification of such variants may potentially allow for early identification of at risk patients. Here we review the current understanding of the key molecular mechanisms and genetic architecture of DN, and discuss the merits of employing an integrative approach to incorporate datasets from multiple sources (genetics, transcriptomics, epigenetic, proteomic) in order to fully elucidate the genetic elements contributing to this serious complication of diabetes. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
Open AccessReview Monogenic Diabetes: A Diagnostic Algorithm for Clinicians
Genes 2013, 4(4), 522-535; doi:10.3390/genes4040522
Received: 15 July 2013 / Revised: 30 August 2013 / Accepted: 2 September 2013 / Published: 26 September 2013
Cited by 4 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text
Abstract
Monogenic forms of beta cell diabetes account for approximately 1%–2% of all cases of diabetes, yet remain underdiagnosed. Overlapping clinical features with common forms of diabetes, make diagnosis challenging. A genetic diagnosis of monogenic diabetes in many cases alters therapy, affects prognosis, enables
[...] Read more.
Monogenic forms of beta cell diabetes account for approximately 1%–2% of all cases of diabetes, yet remain underdiagnosed. Overlapping clinical features with common forms of diabetes, make diagnosis challenging. A genetic diagnosis of monogenic diabetes in many cases alters therapy, affects prognosis, enables genetic counseling, and has implications for cascade screening of extended family members. We describe those types of monogenic beta cell diabetes which are recognisable by distinct clinical features and have implications for altered management; the cost effectiveness of making a genetic diagnosis in this setting; the use of complementary diagnostic tests to increase the yield among the vast majority of patients who will have commoner types of diabetes which are summarised in a clinical algorithm; and the vital role of cascade genetic testing to enhance case finding. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
Open AccessReview Genes Involved in Type 1 Diabetes: An Update
Genes 2013, 4(3), 499-521; doi:10.3390/genes4030499
Received: 31 July 2013 / Revised: 26 August 2013 / Accepted: 5 September 2013 / Published: 16 September 2013
Cited by 9 | PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
Type 1 Diabetes (T1D) is a chronic multifactorial disease with a strong genetic component, which, through interactions with specific environmental factors, triggers disease onset. T1D typically manifests in early to mid childhood through the autoimmune destruction of pancreatic β cells resulting in a
[...] Read more.
Type 1 Diabetes (T1D) is a chronic multifactorial disease with a strong genetic component, which, through interactions with specific environmental factors, triggers disease onset. T1D typically manifests in early to mid childhood through the autoimmune destruction of pancreatic β cells resulting in a lack of insulin production. Historically, prior to genome-wide association studies (GWAS), six loci in the genome were fully established to be associated with T1D. With the advent of high-throughput single nucleotide polymorphism (SNP) genotyping array technologies, enabling investigators to perform high-density GWAS, many additional T1D susceptibility genes have been discovered. Indeed, recent meta-analyses of multiple datasets from independent investigators have brought the tally of well-validated T1D disease genes to almost 60. In this mini-review, we address recent advances in the genetics of T1D and provide an update on the latest susceptibility loci added to the list of genes involved in the pathogenesis of T1D. Full article
(This article belongs to the Special Issue Genetics of Diabetes)

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