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Genes involved in type 1 diabetes: an update.

Bakay M, Pandey R, Hakonarson H - Genes (Basel) (2013)

Bottom Line: Historically, prior to genome-wide association studies (GWAS), six loci in the genome were fully established to be associated with T1D.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. bakay@email.chop.edu.

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 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.

No MeSH data available.


Related in: MedlinePlus

Immune and Non-immune T1D genes. The discovery of T1D susceptibility genes started as early as 1974, with six T1D genes identified by 2006. The advent of GWAS led to flurry of novel genes associated with T1D reaching the excess of 40 by 2009 and almost 60 by 2012.
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genes-04-00499-f002: Immune and Non-immune T1D genes. The discovery of T1D susceptibility genes started as early as 1974, with six T1D genes identified by 2006. The advent of GWAS led to flurry of novel genes associated with T1D reaching the excess of 40 by 2009 and almost 60 by 2012.

Mentions: In T1D this system breaks down: insulin-producing β-cells are subjected to specific attack by the host immune system. To better understand the etiology of T1D for prevention and cure, a plethora of research has been done to link the systematic destruction of β-cells and the role of the immune system, however the exact mechanism of T1D pathogenesis is not completely elucidated. Linkage studies in the 1970s revealed MHC as the first key contributor to T1D susceptibility [8,9,10]. Further linkage analysis and candidate gene association studies uncovered additional T1D loci. Starting in 2007, GWAS has increased the number of loci associated with T1D to almost 60 [38]. As T1D is an immune-mediated disorder the majority of candidate genes exert their functions in immune cells. In Figure 2, we have made an attempt to classify all 59 T1D susceptibility loci/genes in keeping with their predominant function of either non-immune (14) vs. immune (45). However, recent studies indicate that many T1D candidate genes are also expressed in human islets suggesting that functions are not restricted to immune cells, but also play roles in the islets and β cells [48]. The functional aspects of some of the most interesting genes or biological pathways are discussed below.


Genes involved in type 1 diabetes: an update.

Bakay M, Pandey R, Hakonarson H - Genes (Basel) (2013)

Immune and Non-immune T1D genes. The discovery of T1D susceptibility genes started as early as 1974, with six T1D genes identified by 2006. The advent of GWAS led to flurry of novel genes associated with T1D reaching the excess of 40 by 2009 and almost 60 by 2012.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924830&req=5

genes-04-00499-f002: Immune and Non-immune T1D genes. The discovery of T1D susceptibility genes started as early as 1974, with six T1D genes identified by 2006. The advent of GWAS led to flurry of novel genes associated with T1D reaching the excess of 40 by 2009 and almost 60 by 2012.
Mentions: In T1D this system breaks down: insulin-producing β-cells are subjected to specific attack by the host immune system. To better understand the etiology of T1D for prevention and cure, a plethora of research has been done to link the systematic destruction of β-cells and the role of the immune system, however the exact mechanism of T1D pathogenesis is not completely elucidated. Linkage studies in the 1970s revealed MHC as the first key contributor to T1D susceptibility [8,9,10]. Further linkage analysis and candidate gene association studies uncovered additional T1D loci. Starting in 2007, GWAS has increased the number of loci associated with T1D to almost 60 [38]. As T1D is an immune-mediated disorder the majority of candidate genes exert their functions in immune cells. In Figure 2, we have made an attempt to classify all 59 T1D susceptibility loci/genes in keeping with their predominant function of either non-immune (14) vs. immune (45). However, recent studies indicate that many T1D candidate genes are also expressed in human islets suggesting that functions are not restricted to immune cells, but also play roles in the islets and β cells [48]. The functional aspects of some of the most interesting genes or biological pathways are discussed below.

Bottom Line: Historically, prior to genome-wide association studies (GWAS), six loci in the genome were fully established to be associated with T1D.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. bakay@email.chop.edu.

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 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.

No MeSH data available.


Related in: MedlinePlus