Abstract:
:Osteoarthritis is a common, complex disease with no curative therapy. In this review, we summarize current knowledge on disease aetiopathogenesis and outline genetics and genomics approaches that are helping catalyse a much-needed improved understanding of the biological underpinning of disease development and progression.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Cibrián Uhalte E,Wilkinson JM,Southam L,Zeggini Edoi
10.1093/hmg/ddx302subject
Has Abstractpub_date
2017-10-01 00:00:00pages
R193-R201issue
R2eissn
0964-6906issn
1460-2083pii
4039909journal_volume
26pub_type
杂志文章,评审abstract::Cytosolic accumulation of TAR DNA binding protein 43 (TDP-43) is a major neuropathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms involved in TDP-43 accumulation remain largely unknown. Previously, we reported that inhibitors of cyclin-depen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu578
更新日期:2015-03-15 00:00:00
abstract::While several high-resolution recombination maps exist for European-descent populations, the recombination landscape of African populations remains relatively understudied. Given that there is high genetic divergence among groups in Africa, it is possible that recombination hotspots also diverge significantly. Both li...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddab020
更新日期:2021-01-14 00:00:00
abstract::HTRA2-BETA1 is an SR-like protein that regulates alternative splice site selection in a concentration-dependent manner. Its proper concentration is important as several pathological states are associated with its change. We investigated the mechanism that controls the cellular HTRA2-BETA1 concentration and found it ut...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh051
更新日期:2004-03-01 00:00:00
abstract::Although genetic variations in several genes encoding for synaptic adhesion proteins have been found to be associated with autism spectrum disorders, one of the most consistently replicated genes has been CNTNAP2, encoding for contactin-associated protein-like 2 (CASPR2), a multidomain transmembrane protein of the neu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds320
更新日期:2012-11-01 00:00:00
abstract::We have used the direct cDNA screening protocol to identify sequences transcribed in cerebral cortex from a reference library of human Xq28. To derive coding sequences from these genomic clones, we first identified fragments containing transcribed sequences and subjected these to exon trapping or to partial sequencing...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.11.2019
更新日期:1994-11-01 00:00:00
abstract::Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr308
更新日期:2011-10-15 00:00:00
abstract::Most quantitative trait loci (QTL) studies have focused on detecting the genetic effects of individual QTLs. This study thoroughly dissected the genetic components of type 2 diabetic mice, including a search for epistatic interactions and multi-locus additive effects that result in variation in diabetes-related phenot...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi433
更新日期:2006-01-01 00:00:00
abstract::Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1α of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which resu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu265
更新日期:2014-10-15 00:00:00
abstract::Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage me...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddw181
更新日期:2016-08-01 00:00:00
abstract::KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr399
更新日期:2011-12-01 00:00:00
abstract::Splicing regulation is an important step of post-transcriptional gene regulation. It is a highly dynamic process orchestrated by RNA-binding proteins (RBPs). RBP dysfunction and global splicing dysregulation have been implicated in many human diseases, but the in vivo functions of most RBPs and the splicing outcome up...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw337
更新日期:2016-12-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is reta...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn426
更新日期:2009-03-15 00:00:00
abstract::Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage disorder of childhood, is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated (palmitoylated) proteins and its mutation causes abnormal intracellular accumulation of fatty-acy...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl105
更新日期:2006-06-01 00:00:00
abstract::Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been studied both by DNA sequencing and by emerin protein expression. Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal inheritance. Twelve of the 14 emerin mutations caused early termination of translation...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.5.855
更新日期:1998-05-01 00:00:00
abstract::Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1177
更新日期:1997-07-01 00:00:00
abstract::Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene coding for α-galactosidase A (α-GalA). The deleterious mutations lead to accumulation of α-GalA substrates, including globotriaosylceramide (Gb3) and globotriaosylsphingosine. Progressive glycolipid storage results in cellular ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy248
更新日期:2018-10-01 00:00:00
abstract::Genome-wide association studies (GWASs) identified over 500 single nucleotide polymorphisms (SNPs) influencing cancer risk. It is logical to expect the cancer-associated genes to cluster in pathways directly involved in carcinogenesis, e.g. cell cycle. Nevertheless, analyses of the GWAS-detected cancer risk genes usua...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx050
更新日期:2017-04-15 00:00:00
abstract::Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. Th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.3.221
更新日期:2001-02-01 00:00:00
abstract::Meiotic crossovers in the human genome cluster into highly localized hotspots identifiable indirectly from patterns of DNA diversity and directly by high-resolution sperm typing. Little is known about factors that control hotspot activity and the apparently rapid turnover of hotspots during recent evolution. Clues can...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl063
更新日期:2006-05-01 00:00:00
abstract::Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltrans...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp110
更新日期:2009-06-01 00:00:00
abstract::Synapse abnormalities in Huntington's disease (HD) patients can precede clinical diagnosis and neuron loss by decades. The polyglutamine expansion in the huntingtin (htt) protein that underlies this disorder leads to perturbations in many cellular pathways, including the disruption of Rab11-dependent endosomal recycli...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds117
更新日期:2012-07-01 00:00:00
abstract::Huntington's disease (HD) is caused by expansion of a glutamine repeat in huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients and >60 repeats in juvenile HD patients. An N-terminal fragment of mutant huntingtin forms aggregates in neuronal nuclei in the brains of transgenic mice and HD patients. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.5.777
更新日期:1998-05-01 00:00:00
abstract::Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt015
更新日期:2013-04-15 00:00:00
abstract::By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA library of a human skeletal muscle, we identified 1945 individual transcripts, 725 of which showed no correspondence with known human genes. We report here the chromosomal localization of 267 of these, obtained by radiation hybrid (RH) mapping....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1445
更新日期:1997-09-01 00:00:00
abstract::Diabetic retinopathy is a leading cause of blindness. The purpose of this study is to identify novel genetic loci associated with the sight threatening complications of diabetic retinopathy. We performed a meta-analysis of genome-wide association data for severe diabetic retinopathy as defined by diabetic macular edem...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddr121
更新日期:2011-06-15 00:00:00
abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mou...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.13.2009
更新日期:2000-08-12 00:00:00
abstract::Prader-Willi syndrome (PWS) is caused by the loss of expression of imprinted genes in chromosome 15q11-q13. Affected individuals exhibit neonatal hypotonia, developmental delay and childhood-onset obesity. Necdin, a protein implicated in the terminal differentiation of neurons, is the only PWS candidate gene to reduce...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.12.1813
更新日期:2000-07-22 00:00:00
abstract::The polymorphic K variant of the butyrylcholinesterase ( BCHE-K ) gene recently has been demonstrated to have an elevated frequency in Alzheimer's disease (AD) patients carrying the epsilon4 allele of the apolipoprotein (APO E) gene when compared with a control population. We therefore genotyped a large series of path...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.5.937
更新日期:1998-05-01 00:00:00
abstract::Recombination, demographic history, drift and selection influence the extent of linkage disequilibrium (LD) in the human genome, but their relative contributions remain unclear. To investigate the effect of meiotic recombination versus population history on LD, three populations with different demographic histories (U...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg008
更新日期:2003-01-01 00:00:00
abstract::Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp278
更新日期:2009-09-15 00:00:00