解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Even though heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors, previous studies have not explained a large part of the genetics behind these diseases. In this genome-wide association study, we include 346 545 Caucasians from the UK Biobank to identify novel ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz175
更新日期:2019-12-01 00:00:00
abstract::A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddz196
更新日期:2019-11-21 00:00:00
abstract::A main strategy for lowering plasma low-density lipoprotein (LDL) cholesterol levels is to increase the number of cell-surface LDL receptors (LDLRs). This can be achieved by increasing the synthesis or preventing the degradation of the LDLR. One mechanism by which an LDLR becomes non-functional is enzymatic cleavage w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz164
更新日期:2019-11-15 00:00:00
abstract::Wolfram syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and ne...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz212
更新日期:2019-11-15 00:00:00
abstract::BCS1L encodes a homolog of the Saccharomyces cerevisiae bcs1 protein, which has a known role in the assembly of Complex III of the mitochondrial respiratory chain. Phenotypes reported in association with pathogenic BCS1L variants include growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz202
更新日期:2019-11-15 00:00:00
abstract::We report the case of a consanguineous couple who lost four pregnancies associated with skeletal dysplasia. Radiological examination of one fetus was inconclusive. Parental exome sequencing showed that both parents were heterozygous for a novel missense variant, p.(Pro133Leu), in the SLC35D1 gene encoding a nucleotide...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz200
更新日期:2019-11-01 00:00:00
abstract::Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz207
更新日期:2019-11-01 00:00:00
abstract::Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularizatio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz159
更新日期:2019-10-15 00:00:00
abstract::Williams syndrome (WS) is a neurodevelopmental disorder caused by a 1.5-1.8 Mbp deletion on chromosome 7q11.23, affecting the copy number of 26-28 genes. Phenotypes of WS include cardiovascular problems, craniofacial dysmorphology, deficits in visual-spatial cognition and a characteristic hypersocial personality. Ther...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz176
更新日期:2019-10-15 00:00:00
abstract::Understanding the biological functions of tau variants can illuminate differential etiologies of Alzheimer's disease (AD) and primary tauopathies. Though the end-stage neuropathological attributes of AD and primary tauopathies are similar, the etiology and behavioral outcomes of these diseases follow unique and diverg...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz151
更新日期:2019-10-01 00:00:00
abstract::Cystic fibrosis (CF) is a multiorgan recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Gene therapy efforts have focused on treating the lung, since it manifests the most significant life-threatening disease. Over two decades have past since the first...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddz139
更新日期:2019-10-01 00:00:00
abstract::Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated wit...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddz161
更新日期:2019-10-01 00:00:00
abstract::Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz110
更新日期:2019-09-15 00:00:00
abstract::X-linked juvenile retinoschisis (XLRS) is an early-onset inherited condition that affects primarily males and is characterized by cystic lesions of the inner retina, decreased visual acuity and contrast sensitivity and a selective reduction of the electroretinogram (ERG) b-wave. Although XLRS is genetically heterogene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz122
更新日期:2019-09-15 00:00:00
abstract::Ryanodine receptor type I (RYR1)-related myopathies (RYR1 RM) are a clinically and histopathologically heterogeneous group of conditions that represent the most common subtype of childhood onset non-dystrophic muscle disorders. There are no treatments for this severe group of diseases. A major barrier to therapy devel...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz105
更新日期:2019-09-15 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could redu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz086
更新日期:2019-08-15 00:00:00
abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz094
更新日期:2019-08-15 00:00:00
abstract::Parkinson's disease (PD) is associated with olfactory defects in addition to dopaminergic degeneration. Dopaminergic signalling is necessary for subventricular zone (SVZ) proliferation and olfactory bulb (OB) neurogenesis. Alpha-synuclein (α-syn or Snca) modulates dopaminergic neurotransmission, and SNCA mutations cau...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz057
更新日期:2019-07-15 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD is characterized by mutations in the dystrophin gene that result in a loss of the dystrophin protein. Loss of dystrophin causes an associated reduction in proteins of the dystrophin glycoprotein...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz044
更新日期:2019-07-01 00:00:00
abstract::Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz056
更新日期:2019-07-01 00:00:00
abstract::Understanding the role of the epigenome in protein-misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable response of the disease population to therapeutics. An ever-growing body of evidence has shown ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz026
更新日期:2019-06-15 00:00:00
abstract::Titin-truncating variants (TTNtv) are the most common genetic cause of dilated cardiomyopathy. TTNtv occur in ~1% of the general population and causes subclinical cardiac remodeling in asymptomatic carriers. In rat models with either proximal or distal TTNtv, we previously showed altered cardiac metabolism at baseline...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz033
更新日期:2019-06-15 00:00:00
abstract::Plasmalogens, the most prominent ether (phospho)lipids in mammals, are structural components of most cellular membranes. Due to their physicochemical properties and abundance in the central nervous system, a role of plasmalogens in neurotransmission has been proposed, but conclusive data are lacking. Here, we targeted...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz040
更新日期:2019-06-15 00:00:00
abstract::Protein engineering is a means to optimize protein therapeutics developed for the treatment of so far incurable diseases including cancers and genetic disorders. Here we report on an engineering approach in which we successfully increased the catalytic rate constant of an enzyme that is presently evaluated in enzyme r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz020
更新日期:2019-06-01 00:00:00
abstract::Missense mutations in the gene, MAP3K1, are a common cause of 46,XY gonadal dysgenesis, accounting for 15-20% of cases [Ostrer, 2014, Disorders of sex development (DSDs): an update. J. Clin. Endocrinol. Metab., 99, 1503-1509]. Functional studies demonstrated that all of these mutations cause a protein gain-of-function...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz002
更新日期:2019-05-15 00:00:00
abstract::Nebulin is a large skeletal muscle protein wound around the thin filaments, with its C-terminus embedded within the Z-disk and its N-terminus extending out toward the thin filament pointed end. While nebulin's C-terminus has been implicated in both sarcomeric structure and function as well as the development of nemali...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz016
更新日期:2019-05-15 00:00:00
abstract::Hand-Foot-Genital syndrome is a rare condition caused by mutations in the HOXA13 gene and characterized by limb malformations and urogenital defects. While the role of Hoxa13 in limb development has been extensively studied, its function during the development of the urogenital system remains elusive mostly due to the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz013
更新日期:2019-05-15 00:00:00
abstract::Mitochondria contain a dedicated translation system, which is responsible for the intramitochondrial synthesis of 13 mitochondrial DNA (mtDNA)-encoded polypeptides essential for the biogenesis of oxidative phosphorylation (OXPHOS) complexes I and III-V. Mutations in nuclear genes encoding factors involved in mitochond...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy441
更新日期:2019-05-01 00:00:00
abstract::Long non-coding RNAs (lncRNAs) are post-transcriptional and epigenetic regulators, whose implication in neurodegenerative and autoimmune diseases remains poorly understood. We analyzed publicly available microarray data sets to identify dysregulated lncRNAs in multiple sclerosis (MS), a neuroinflammatory autoimmune di...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy438
更新日期:2019-05-01 00:00:00
abstract::Epilepsy, deafness, onychodystrophy, osteodystrophy and intellectual disability are associated with a spectrum of mutations of human TBC1D24. The mechanisms underlying TBC1D24-associated disorders and the functions of TBC1D24 are not well understood. Using CRISPR-Cas9 genome editing, we engineered a mouse with a prema...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy445
更新日期:2019-05-01 00:00:00
abstract::Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy420
更新日期:2019-04-15 00:00:00
abstract::Interpretation of genetic association results is difficult because signals often lack biological context. To generate hypotheses of the functional genetic etiology of complex cardiometabolic traits, we estimated the genetically determined component of gene expression from common variants using PrediXcan (1) and determ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy435
更新日期:2019-04-01 00:00:00
abstract::Prolactinomas are the most frequent type of pituitary tumors, which represent 10-20% of all intracranial neoplasms in humans. Prolactinomas develop in mice lacking the prolactin receptor (PRLR), which is a member of the cytokine receptor superfamily that signals via Janus kinase-2-signal transducer and activator of tr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy396
更新日期:2019-03-15 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is among the most common monogenic disorders mainly associated with PKD1/PC1 mutations. We show herein that renal regulation in Pc1 dosage-reduced and -increased mouse models converge toward stimulation of c-Myc expression along with β-catenin, delineating c-Myc as ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy379
更新日期:2019-03-01 00:00:00
abstract::Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy358
更新日期:2019-02-15 00:00:00
abstract::Mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders, from drug-refractory lethal epileptic encephalopathy and DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures) to non-syndromic hearing loss...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy370
更新日期:2019-02-15 00:00:00
abstract::Dysfunction of mitochondrial translation is an increasingly important molecular cause of human disease, but structural defects of mitochondrial ribosomal subunits are rare. We used next-generation sequencing to identify a homozygous variant in the mitochondrial small ribosomal protein 14 (MRPS14, uS14m) in a patient m...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy374
更新日期:2019-02-15 00:00:00
abstract::Angelman syndrome, Prader-Will syndrome and Dup15q syndrome map to a cluster of imprinted genes located at 15q11-q13. Imprinting at this domain is regulated by an imprinting control region consisting of two distinct elements, the Angelman syndrome imprinting center (AS-IC) and the Prader-Willi syndrome imprinting cent...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy345
更新日期:2019-01-15 00:00:00
abstract::Cornelia de Lange syndrome (CdLS), which is reported to affect ∼1 in 10 000 to 30 000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition. CdLS can result from mutations in at least five ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy329
更新日期:2019-01-01 00:00:00
abstract::Polycystin-1 (PC1), encoded by the PKD1 gene that is mutated in the autosomal dominant polycystic kidney disease, regulates a number of processes including bone development. Activity of the transcription factor RunX2, which controls osteoblast differentiation, is reduced in Pkd1 mutant mice but the mechanism governing...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy322
更新日期:2019-01-01 00:00:00