Abstract:
:The rapid increase in the prevalence of type 2 diabetes (T2D) represents a major challenge for health care delivery worldwide. Identification of genes influencing individual susceptibility to disease offers a route to better understanding of the molecular mechanisms underlying pathogenesis, a necessary prerequisite for the rational development of improved preventative and therapeutic methods. The past decade has seen substantial success in identifying genes responsible for monogenic forms of diabetes (notably, maturity-onset diabetes of the young), and, in patients presenting with early-onset diabetes, a precise molecular diagnosis is an increasingly important element of optimal clinical care. Progress in gene identification for more common, multifactorial forms of type 2 diabetes has been slower, but there is now compelling evidence that common variants in the PPARG, KCNJ11 and CAPN10 genes influence T2D-susceptibility, and positional cloning efforts within replicated regions of linkage promise to deliver additional components of inherited susceptibility. The challenge in the years to come will be to understand how T2D risk is influenced by the interaction of these variants with each other and with pertinent environmental factors encountered during gestation, childhood and adulthood; and to establish how best to apply this understanding to provide individuals with clinically-useful diagnostic, prognostic and therapeutic information.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
McCarthy MIdoi
10.1093/hmg/ddh057subject
Has Abstractpub_date
2004-04-01 00:00:00pages
R33-41eissn
0964-6906issn
1460-2083pii
ddh057journal_volume
13 Spec No 1pub_type
杂志文章,评审abstract::Renal-coloboma syndrome, also known as papillorenal syndrome, is an autosomal dominant human disorder in which optic disc coloboma is associated with kidney abnormalities. Mutations in the paired domain transcription factor PAX2 have been found to be the underlying cause of this disease. Disease severity varies betwee...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq457
更新日期:2011-01-15 00:00:00
abstract::A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm136
更新日期:2007-10-15 00:00:00
abstract::Linkage, association and postmortem studies have implicated regulator of G-protein signaling 4 (RGS4), which negatively modulates signal transduction at G-protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC), between...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl222
更新日期:2006-09-15 00:00:00
abstract::The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an in...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp119
更新日期:2009-06-01 00:00:00
abstract::Spinal and bulbar muscular atrophy (SBMA, also known as Kennedy's disease) is one of nine neurodegenerative disorders that are caused by expansion of polyglutamine-encoding CAG repeats. Intracellular accumulation of abnormal proteins in these diseases, a pathological hallmark, is associated with defects in protein hom...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw073
更新日期:2016-05-15 00:00:00
abstract::Extracellular deposition of amyloid-beta (Aβ) peptide, a metabolite of sequential cleavage of amyloid precursor protein (APP), is a critical step in the pathogenesis of Alzheimer's disease (AD). While death-associated protein kinase 1 (DAPK1) is highly expressed in AD brains and its genetic variants are linked to AD r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw114
更新日期:2016-06-15 00:00:00
abstract::Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disease that has been linked to deletions within a tandem array of 3.2 kb repeats adjacent to the telomere of 4q. These repeats are also present in other locations in the human genome, including the short arms of all the acrocentric c...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.10.1567
更新日期:1996-10-01 00:00:00
abstract::Missing teeth (hypodontia and oligodontia) are a common developmental abnormality in humans and heterozygous mutations of PAX9 have recently been shown to underlie a number of familial, non-syndromic cases. Whereas PAX9 haploinsufficiency has been suggested as the underlying genetic mechanism, it is not known how this...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi388
更新日期:2005-12-01 00:00:00
abstract::Circletail is one of only two mouse mutants that exhibit the most severe form of neural tube defect (NTD), termed craniorachischisis. In this disorder, almost the entire brain and spinal cord is affected, owing to a failure to initiate neural tube closure. Craniorachischisis is a significant cause of lethality in huma...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg014
更新日期:2003-01-15 00:00:00
abstract::Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the unde...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy310
更新日期:2018-12-15 00:00:00
abstract::Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx178
更新日期:2017-08-15 00:00:00
abstract::We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a min...
journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
doi:10.1093/hmg/ddt403
更新日期:2014-01-01 00:00:00
abstract::An infant presented with fatal infantile lactic acidosis and cardiomyopathy, and was found to have profoundly decreased activity of respiratory chain complex I in muscle, heart and liver. Exome sequencing revealed compound heterozygous mutations in NDUFB10, which encodes an accessory subunit located within the PD part...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw431
更新日期:2017-02-15 00:00:00
abstract::Proximal spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron gene (SMN1). In humans, two nearly identical copies of SMN exist and differ only by a single non-polymorphic C-->T nucleotide transition in exon 7. SMN1 contains a 'C' nucleotide at the +6 position of exon 7 and produces primari...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.23.2727
更新日期:2001-11-01 00:00:00
abstract::Melanomas contain high frequencies of tumorigenic cells and their tumorigenic capacity resides in several distinct subpopulations within melanoma. Since their metastatic potential is linked to their ability to recruit lymphatic vessels, we aimed at identifying lymphangiogenic subpopulations by comparative in vitro ana...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds171
更新日期:2012-08-01 00:00:00
abstract::Progressive myoclonus epilepsy of Lafora type (LD, MIM 254780) is a fatal autosomal recessive disorder characterized by the presence of progressive neurological deterioration, myoclonus, epilepsy and polyglucosan intracellular inclusion bodies, called Lafora bodies. Lafora bodies resemble glycogen with reduced branchi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg340
更新日期:2003-12-01 00:00:00
abstract::Peroxisome biogenesis disorders, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease, are lethal hereditary diseases caused by abnormalities in peroxisomal assembly. To date, 12 genotypes have been identified. We now have evidence that the complete human cDNA encoding P...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.6.1077
更新日期:1999-06-01 00:00:00
abstract::Fatty liver has been associated with unfavourable metabolic changes in circulation. To provide insights in fatty liver-related metabolic deviations, we compared metabolic association profile of fatty liver versus metabolic association profiles of genotypes increasing the risk of non-alcoholic fatty liver disease (NAFL...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy124
更新日期:2018-06-15 00:00:00
abstract::Valosin-containing protein (VCP)-associated disease caused by mutations in the VCP gene includes combinations of a phenotypically heterogeneous group of disorders such as hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis. Currently, there are no effe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt523
更新日期:2014-03-01 00:00:00
abstract::By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain. The Bcl2-L-10 gene has been assigned to chromosome 15q21.2. Transfection experiments demonstrated that Bcl2-L-10 can block apoptosis induced by inter...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.21.2329
更新日期:2001-10-01 00:00:00
abstract::We have recently described the identification of a second IDS locus (IDS-2) located within 90 kb telomeric of the IDS gene (Bondeson et al. submitted). Here, we show that this region is involved in a recombination event with the IDS gene in about 13% of patients with the Hunter syndrome. Analysis of the resulting rear...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.615
更新日期:1995-04-01 00:00:00
abstract::Cytochrome c oxidase (COX) defects are found in a clinically and genetically heterogeneous group of mitochondrial disorders. To date, mutations in only two nuclear genes causing COX deficiency have been described. We report here a genetic linkage study of a consanguineous family with an isolated COX defect and subsequ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.8.1245
更新日期:2000-05-01 00:00:00
abstract::Ciliary trafficking defects underlie the pathogenesis of severe human ciliopathies, including Joubert Syndrome (JBTS), Bardet-Biedl Syndrome, and some forms of retinitis pigmentosa (RP). Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are common causes of RP-associated photoreceptor degen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw281
更新日期:2016-10-15 00:00:00
abstract::It is now well established that the genomic landscape of DNA methylation (DNAm) gets altered as a function of age, a process we here call 'epigenetic drift'. The biological, functional, clinical and evolutionary significance of this epigenetic drift, however, remains unclear. We here provide a brief review of epigenet...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt375
更新日期:2013-10-15 00:00:00
abstract::The EPM2A gene, encoding the dual-phosphatase laforin, is mutated in a fatal form of progressive myoclonus epilepsy known as Lafora disease (LD). The EPM2A gene, by differential splicing of its transcripts, is known to encode two laforin isoforms having distinct carboxyl termini; a major isoform localized in the cytop...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn199
更新日期:2008-10-01 00:00:00
abstract::Mitochondrial dysfunction plays an important role in the etiology of neurodegenerative diseases. However, the progressive nature of neuronal loss in genetic models of mitochondrial dysfunction suggests the presence of compensatory mechanisms promoting neuronal survival under these conditions. Here, we identified the e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds500
更新日期:2013-03-01 00:00:00
abstract::Expansion of a polyglutamine tract in ataxin-3 (AT3) results in spinocerebellar ataxia type 3/Machado-Joseph disease, one of the nine polyglutamine neurodegenerative diseases. Understanding the normal functions of AT3 as well as its function in the context of expansion of the polyglutamine tract is critical for unders...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl164
更新日期:2006-08-15 00:00:00
abstract::TNNI3K expression worsens disease progression in several mouse heart pathology models. TNNI3K expression also reduces the number of diploid cardiomyocytes, which may be detrimental to adult heart regeneration. However, the gene is evolutionarily conserved, suggesting a beneficial function that has remained obscure. He...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa234
更新日期:2021-01-06 00:00:00
abstract::Genome-wide association studies of colorectal cancer (CRC) have identified a number of common variants associated with modest risk, including rs3802842 at chromosome 11q23.1. Several genes map to this region but rs3802842 does not map to any known transcribed or regulatory sequences. We reasoned, therefore, that rs380...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt584
更新日期:2014-04-15 00:00:00
abstract::Steroid 11 beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol. Severely affected patients carry mutations in the CYB11B1 gene that destroy enzymatic activity. Such patients have signs of androgen excess and usually have hyperten...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.11.1829
更新日期:1997-10-01 00:00:00