Dataset Information

New insights from monogenic diabetes for "common" type 2 diabetes.

ABSTRACT: Boundaries between monogenic and complex genetic diseases are becoming increasingly blurred, as a result of better understanding of phenotypes and their genetic determinants. This had a large impact on the way complex disease genetics is now being investigated. Starting with conventional approaches like familial linkage, positional cloning and candidate genes strategies, the scope of complex disease genetics has grown exponentially with scientific and technological advances in recent times. Despite identification of multiple loci harboring common and rare variants associated with complex diseases, interpreting and evaluating their functional role has proven to be difficult. Information from monogenic diseases, especially related to the intermediate traits associated with complex diseases comes handy. The significant overlap between traits and phenotypes of monogenic diseases with related complex diseases provides a platform to understand the disease biology better. In this review, we would discuss about one such complex disease, type 2 diabetes, which shares marked similarity of intermediate traits with different forms of monogenic diabetes.

SUBMITTER: Tallapragada DS

PROVIDER: S-EPMC4528293 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New insights from monogenic diabetes for "common" type 2 diabetes.

Tallapragada Divya Sri Priyanka DS Bhaskar Seema S Chandak Giriraj R GR

Frontiers in genetics 20150807

Boundaries between monogenic and complex genetic diseases are becoming increasingly blurred, as a result of better understanding of phenotypes and their genetic determinants. This had a large impact on the way complex disease genetics is now being investigated. Starting with conventional approaches like familial linkage, positional cloning and candidate genes strategies, the scope of complex disease genetics has grown exponentially with scientific and technological advances in recent times. Desp ...[more]

PMID: 26300908

Similar Datasets

Project description:To date, more than 30 genes have been linked to monogenic diabetes. Candidate gene and genome-wide association studies have identified > 50 susceptibility loci for common type 1 diabetes (T1D) and approximately 100 susceptibility loci for type 2 diabetes (T2D). About 1-5% of all cases of diabetes result from single-gene mutations and are called monogenic diabetes. Here, we review the pathophysiological basis of the role of monogenic diabetes genes that have also been found to be associated with common T1D and/or T2D. Variants of approximately one-third of monogenic diabetes genes are associated with T2D, but not T1D. Two of the T2D-associated monogenic diabetes genes-potassium inward-rectifying channel, subfamily J, member 11 (KCNJ11), which controls glucose-stimulated insulin secretion in the ?-cell; and peroxisome proliferator-activated receptor ? (PPARG), which impacts multiple tissue targets in relation to inflammation and insulin sensitivity-have been developed as major antidiabetic drug targets. Another monogenic diabetes gene, the preproinsulin gene (INS), is unique in that INS mutations can cause hyperinsulinemia, hyperproinsulinemia, neonatal diabetes mellitus, one type of maturity-onset diabetes of the young (MODY10), and autoantibody-negative T1D. Dominant heterozygous INS mutations are the second most common cause of permanent neonatal diabetes. Moreover, INS gene variants are strongly associated with common T1D (type 1a), but inconsistently with T2D. Variants of the monogenic diabetes gene Gli-similar 3 (GLIS3) are associated with both T1D and T2D. GLIS3 is a key transcription factor in insulin production and ?-cell differentiation during embryonic development, which perturbation forms the basis of monogenic diabetes as well as its association with T1D. GLIS3 is also required for compensatory ?-cell proliferation in adults; impairment of this function predisposes to T2D. Thus, monogenic forms of diabetes are invaluable "human models" that have contributed to our understanding of the pathophysiological basis of common T1D and T2D.

Project description:Osteoporosis, characterized by deteriorated bone microarchitecture and low bone mineral density, is a chronic skeletal disease with high worldwide prevalence. Osteoporosis related to aging is the most common form and causes significant morbidity and mortality. Rare, monogenic forms of osteoporosis have their onset usually in childhood or young adulthood and have specific phenotypic features and clinical course depending on the underlying cause. The most common form is osteogenesis imperfecta linked to mutations in COL1A1 and COL1A2, the two genes encoding type I collagen. However, in the past years, remarkable advancements in bone research have expanded our understanding of the intricacies behind bone metabolism and identified novel molecular mechanisms contributing to skeletal health and disease. Especially high-throughput sequencing techniques have made family-based studies an efficient way to identify single genes causative of rare monogenic forms of osteoporosis and these have yielded several novel genes that encode proteins partaking in type I collagen modification or regulating bone cell function directly. New forms of monogenic osteoporosis, such as autosomal dominant osteoporosis caused by WNT1 mutations or X-linked osteoporosis due to PLS3 mutations, have revealed previously unidentified bone-regulating proteins and clarified specific roles of bone cells, expanded our understanding of possible inheritance mechanisms and paces of disease progression, and highlighted the potential of monogenic bone diseases to extend beyond the skeletal tissue. The novel gene discoveries have introduced new challenges to the classification and diagnosis of monogenic osteoporosis, but also provided promising new molecular targets for development of pharmacotherapies. In this article we give an overview of the recent discoveries in the area of monogenic forms of osteoporosis, describing the key cellular mechanisms leading to skeletal fragility, the major recent research findings and the essential challenges and avenues in future diagnostics and treatments.

Dataset Information

New insights from monogenic diabetes for "common" type 2 diabetes.

Publications

New insights from monogenic diabetes for "common" type 2 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets