Abstract:
:The high affinity receptor for IgE (Fc epsilon RI) has a central role in mast cell degranulation and IgE mediated allergy. A systematic search through the coding regions of the beta subunit of Fc epsilon RI (Fc epsilon RI-beta) has identified a novel coding polymorphism in exon seven. An adenine to guanine substitution changes amino acid residue 237 from glutamic acid to glycine (E237G), in the cytoplasmic tail of the protein. E237G is predicted to introduce a hydrophobicity change within the C-terminus of Fc epsilon RI-beta. It is adjacent to the immunoreceptor tyrosine activation motif (ITAM), and may affect the intracellular signalling capacity of Fc epsilon RI. E237G was detected in 53 subjects from an Australian general population sample of 1004 individuals (5.3%). E237G positive subjects had a significantly elevated skin test response to grass (p = 0.0004) and house dust mite (p = 0.04), RAST to grass (p = 0.002) and bronchial reactivity to methacholine (p = 0.0009). The relative risk of individuals with E237G having asthma compared to subjects without the variant was 2.3 (95% CI 1.26-4.19; p = 0.005).
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Hill MR,Cookson WOdoi
10.1093/hmg/5.7.959subject
Has Abstractpub_date
1996-07-01 00:00:00pages
959-62issue
7eissn
0964-6906issn
1460-2083pii
6d0012journal_volume
5pub_type
杂志文章abstract::Parental genetic relatedness may lead to adverse health and fitness outcomes in the offspring. However, the degree to which it affects human delivery timing is unknown. We use genotype data from ≃25 000 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study to optimize runs of homozygosity (RO...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa255
更新日期:2020-12-08 00:00:00
abstract::Reduced sarcolemmal integrity in dystrophin-deficient muscles of mdx mice and Duchenne muscular dystrophy (DMD) patients has been reported to result in altered calcium homeostasis. Previous studies have shown a correlative relationship between calcium-dependent protease (calpain) activity in dystrophic muscle and musc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.21.2645
更新日期:2002-10-01 00:00:00
abstract::The ubiquitin-proteasome system (UPS) is the principal protein degradation system that tags and targets short-lived proteins, as well as damaged or misfolded proteins, for destruction. In spinal and bulbar muscular atrophy (SBMA), the androgen receptor (AR), an Hsp90 client protein, is such a misfolded protein that te...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn419
更新日期:2009-03-01 00:00:00
abstract::A cluster of imprinted genes on human chromosome 15q11-q13 (the PWS/AS domain) and its ortholog on mouse chromosome 7c is believed to be regulated by an imprinting control center. Although minideletions in this region in Angelman syndrome (AS) and Prader-Willi syndrome (PWS) patients revealed that two elements, shorte...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh085
更新日期:2004-04-01 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by the expansion of a polyglutamine tract within the SCA1 product, ataxin-1. Previously, using transgenic mice, it was demonstrated that in order for a mutant allele of ataxin-1 to cause disease it must be transported to the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.1.25
更新日期:2001-01-01 00:00:00
abstract::The term 'dynamic mutation' was introduced to distinguish the unique properties of expanding, unstable DNA repeat sequences from other forms of mutation. The past decade has seen dynamic mutations uncovered as the molecular basis for a growing number of human genetic diseases and for all of the characterized 'rare' ch...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/10.20.2187
更新日期:2001-10-01 00:00:00
abstract::Mutations in the parkin gene, encoding an E3 ubiquitin-protein ligase, are a frequent cause of autosomal recessive parkinsonism and are also involved in sporadic Parkinson's disease. Loss of Parkin function is thought to compromise the polyubiquitylation and proteasomal degradation of specific substrates, leading to t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl131
更新日期:2006-07-01 00:00:00
abstract::Expression of misfolded protein in cultured cells frequently leads to the formation of juxtanuclear inclusions that have been termed 'aggresomes'. Aggresome formation is an active cellular response that involves trafficking of the offending protein along microtubules, reorganization of intermediate filaments and recru...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg074
更新日期:2003-04-01 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds186
更新日期:2012-08-15 00:00:00
abstract::A proportion of human breast cancers result from an inherited predisposition to the disease. Mutations in the BRCA2 gene confer a high risk of breast cancer and are responsible for almost half of these cases. The recent cloning of the human BRCA2 gene has revealed that it encodes a large protein having little signific...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.2.291
更新日期:1997-02-01 00:00:00
abstract::5-Methylcytosine (5mC), generated through the covalent addition of a methyl group to the fifth carbon of cytosine, is the most prevalent DNA modification in humans and functions as a critical player in the regulation of tissue and cell-specific gene expression. 5mC can be oxidized to 5-hydroxymethylcytosine (5hmC) by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz273
更新日期:2020-01-01 00:00:00
abstract::The defective gene responsible for the recessively inherited immunodeficiency X-linked agammaglobulinemia (XLA) has been shown to encode a cytoplasmic protein tyrosine kinase of the Src family designated Btk (Bruton's tyrosine kinase). To facilitate the search for germline mutations of the Btk gene, we have characteri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.10.1743
更新日期:1994-10-01 00:00:00
abstract::Mutations in DJ-1 cause recessively transmitted early-onset Parkinson disease (PD), and oxidative damage to DJ-1 has been associated with the pathogenesis of late-onset sporadic PD. The precise biochemical function of DJ-1 remains elusive. Here, we report that DJ-1 is synthesized as a latent protease zymogen with low-...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq113
更新日期:2010-06-15 00:00:00
abstract::Manipulation of the mouse genome by site-specific mutagenesis has been extensively used to study gene function and model human disorders. Mouse models of myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene, have been generated by homologous recombinatio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt038
更新日期:2013-05-01 00:00:00
abstract::Mutations in fibroblast growth factor receptors (FGFRs) cause human birth defect syndromes and are associated with a variety of cancers. Although forced expression of mutant activated FGFRs has been shown to oncogenically transform some immortal cell types, their activity in primary cells remains unclear. Here, we sho...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp195
更新日期:2009-07-15 00:00:00
abstract::Migraine affects ∼14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine heada...
journal_title:Human molecular genetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1093/hmg/ddw416
更新日期:2017-02-15 00:00:00
abstract::Mutations of mitochondrial DNA are linked to many human diseases. Despite the identification of a large number of variants in the mitochondrially encoded rRNA (mt-rRNA) genes, the evidence supporting their pathogenicity is, at best, circumstantial. Establishing the pathogenicity of these variations is of major diagnos...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt490
更新日期:2014-02-15 00:00:00
abstract::Glucocorticoids are beneficial in Duchenne muscular dystrophy (DMD). Osteopontin (OPN), the protein product of SPP1, plays a role in DMD pathology modulating muscle inflammation and regeneration. A polymorphism in the SPP1 promoter (rs28357094) has been recognized as a genetic modifier of DMD, and there is evidence su...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx218
更新日期:2017-09-01 00:00:00
abstract::The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds233
更新日期:2012-09-15 00:00:00
abstract::An unresolved issue about many neurodegenerative diseases is why neurons are particularly sensitive to defects in ubiquitous cellular processes. One example is Niemann Pick type C1, caused by defects in cholesterol trafficking in all cells, but where neurons are preferentially damaged. Understanding this selective fai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds090
更新日期:2012-06-15 00:00:00
abstract::CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex det...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx398
更新日期:2018-01-01 00:00:00
abstract::Neurons throughout the brain suddenly discharging synchronously and recurrently cause primarily generalized seizures. Discharges localized awhile in one part of the brain cause focal-onset seizures. A genetically determined generalized hyperexcitability had been predicted in primarily generalized seizures, but surpris...
journal_title:Human molecular genetics
pub_type: 更正并重新发布的文章,杂志文章,评审
doi:
更新日期:2005-10-15 00:00:00
abstract::To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygosity in MEN1-associated tumors have localized the MEN1 ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.3.465
更新日期:1994-03-01 00:00:00
abstract::Mutations of the thyroid hormone receptor α gene (THRA) cause hypothyroidism in patients with growth and developmental retardation, and skeletal dysplasia. Genetic evidence indicates that the dominant negative activity of TRα1 mutants underlies pathological manifestations. Using a mouse model of hypothyroidism caused ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt660
更新日期:2014-05-15 00:00:00
abstract::Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of the triple helical domain of collagens. P4HA1 encodes the catalytic α(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connec...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx110
更新日期:2017-06-15 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::Nephropathic cystinosis, a lysosomal storage disease caused by mutations in the CTNS gene encoding the lysosomal cystine transporter cystinosin, is characterized by generalized proximal tubule (PT) dysfunction that progresses, if untreated, to end-stage renal disease. The pathogenesis of defective PT cellular transpor...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt617
更新日期:2014-05-01 00:00:00
abstract::The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx211
更新日期:2017-09-01 00:00:00
abstract::FMR1 protein expression was studied in different tissues. In human, monkey and murine tissues, high molecular mass FMR1 proteins (67-80 kDa) are found, as shown in lymphoblastoid cells lines. The identity of these proteins was confirmed by their absence in tissues from patients with the fragile X syndrome and a FMR1 k...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.5.895
更新日期:1995-05-01 00:00:00