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::Spastic paraplegia 35 (SPG35) (OMIM: 612319) or fatty acid hydroxylase-associated neurodegeneration (FAHN) is caused by deficiency of fatty acid 2-hydroxylase (FA2H). This enzyme synthesizes sphingolipids containing 2-hydroxylated fatty acids, which are particularly abundant in myelin. Fa2h-deficient (Fa2h-/-) mice de...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa246
更新日期:2021-01-21 00:00:00
abstract::OPA1 mutations are the major cause of dominant optic atrophy (DOA) and the syndromic form DOA plus, pathologies for which there is no established cure. We used a 'drug repurposing' approach to identify FDA-approved molecules able to rescue the mitochondrial dysfunctions induced by OPA1 mutations. We screened two diffe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa244
更新日期:2021-01-21 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::Skin color is a highly heritable human trait, and global variation in skin pigmentation has been shaped by natural selection, migration, and admixture. Ethnically diverse African populations harbor extremely high levels of genetic and phenotypic diversity, and skin pigmentation varies widely across Africa. Recent geno...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddab007
更新日期:2021-01-12 00:00:00
abstract::During human spermatogenesis, germ cells undergo dynamic changes in chromatin organization/re-packaging and in transcriptomes. In order to better understand the underlying mechanism(s), scATAC-Seq of 5376 testicular cells from 3 normal men were performed. Data were analyzed in parallel with the scRNA-Seq data of human...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddab006
更新日期:2021-01-12 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::Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa218
更新日期:2021-01-06 00:00:00
abstract::Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neurolig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa232
更新日期:2021-01-06 00:00:00
abstract::SPEG, a member of the myosin light chain kinase family, is localized at the level of triad surrounding myofibrils in skeletal muscles. In humans, SPEG mutations are associated with centronuclear myopathy and cardiomyopathy. Using a striated muscle specific Speg-knockout (KO) mouse model, we have previously shown that ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa276
更新日期:2020-12-23 00:00:00
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::Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa187
更新日期:2020-11-04 00:00:00
abstract::Genome editing to correct a defective β-globin gene or induce fetal globin (HbF) for patients with beta-hemoglobinopathies has the potential to be a curative strategy available to all. HbF reactivation has long been an area of intense interest given the HbF inhibition of sickle hemoglobin (HbS) polymerization. Patient...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa088
更新日期:2020-09-30 00:00:00
abstract::With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa115
更新日期:2020-09-30 00:00:00
abstract::Losing of ovarian functions prior to natural menopause age causes female infertility and early menopause. Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity before 40 years of age. Known genetic causes account for 25-30% of POI cases, demonstrating the high genetic heterogeneity of POI an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa153
更新日期:2020-09-29 00:00:00
abstract::Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed a limited therapeutic time window and systemic aspects of the disease. This raises a fundamental question of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa146
更新日期:2020-09-29 00:00:00
abstract::Loss-of-function mutations of the X-chromosome gene UPF3B cause male neurodevelopmental disorders (NDDs) via largely unknown mechanisms. We investigated initially by interrogating a novel synonymous UPF3B variant in a male with absent speech. In silico and functional studies using cell lines derived from this individu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa151
更新日期:2020-08-29 00:00:00
abstract::Facioscapulohumeral muscular dystrophy (FSHD) is an incurable disorder linked to ectopic expression of DUX4. However, DUX4 is notoriously difficult to detect in FSHD muscle cells, while DUX4 target gene expression is an inconsistent biomarker for FSHD skeletal muscle biopsies, displaying efficacy only on pathologicall...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa053
更新日期:2020-08-11 00:00:00
abstract::Mutations in S-phase cyclin A-associated protein in the endoplasmic reticulum (SCAPER) cause a recessively inherited multisystemic disorder whose main features are retinal degeneration and intellectual disability. SCAPER, originally identified as a cell cycle regulator, was also suggested to be a ciliary protein. Beca...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa113
更新日期:2020-08-03 00:00:00
abstract::Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa107
更新日期:2020-08-03 00:00:00
abstract::The RASopathies are a group of genetic syndromes caused by upregulated RAS signaling. Noonan syndrome (NS), the most common entity among the RASopathies, is characterized mainly by short stature, cardiac anomalies and distinctive facial features. Mutations in multiple RAS-MAPK pathway-related genes have been associate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz108
更新日期:2020-07-21 00:00:00
abstract::Twist1 is a basic helix-loop-helix transcription factor, essential during early development in mammals. While Twist1 induces epithelial-to-mesenchymal transition (EMT), here we show that Twist1 overexpression enhances nuclear and mitotic aberrations. This is accompanied by an increase in whole chromosomal copy number ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa076
更新日期:2020-06-27 00:00:00
abstract::Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia/myopathy, respectively. The mechanism by which they disrupt mitochondrial cristae, however...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa077
更新日期:2020-06-03 00:00:00
abstract::As the powerhouses of the eukaryotic cell, mitochondria must maintain their genomes which encode proteins essential for energy production. Mitochondria are characterized by guanine-rich DNA sequences that spontaneously form unusual three-dimensional structures known as G-quadruplexes (G4). G4 structures can be problem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa043
更新日期:2020-05-28 00:00:00
abstract::During mitosis, Kif11, a kinesin motor protein, promotes bipolar spindle formation and chromosome movement, and during interphase, Kif11 mediates diverse trafficking processes in the cytoplasm. In humans, inactivating mutations in KIF11 are associated with (1) retinal hypovascularization with or without microcephaly a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa018
更新日期:2020-05-08 00:00:00
abstract::Pre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz231
更新日期:2020-05-08 00:00:00
abstract::γ-secretase is a macromolecular complex that catalyzes intramembranous hydrolysis of more than 100 membrane-bound substrates. The complex is composed of presenilin (PS1 or PS2), anterior pharynx defect-1 (APH-1), nicastrin (NCT) and PEN-2 and early-onset; autosomal dominant forms of Alzheimer's disease (AD) are caused...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa017
更新日期:2020-04-15 00:00:00
abstract::Proteolytic fragmentation of polyglutamine-expanded ataxin-3 is a concomitant and modifier of the molecular pathogenesis of Machado-Joseph disease (MJD), the most common autosomal dominant cerebellar ataxia. Calpains, a group of calcium-dependent cysteine proteases, are important mediators of ataxin-3 cleavage and imp...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa010
更新日期:2020-04-15 00:00:00
abstract::Patients with ataxia-telangiectasia (A-T) lack a functional ATM kinase protein and exhibit defective repair of DNA double-stranded breaks and response to oxidative stress. We show that CRISPR/Cas9-assisted gene correction combined with piggyBac (PB) transposon-mediated excision of the selection cassette enables seamle...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa023
更新日期:2020-04-15 00:00:00
abstract::Evidence of the effects of genetic risk score (GRS) on secondary prevention is scarce and mixed. We investigated whether coronary artery disease (CAD) susceptible loci can be used to predict the risk of major adverse cardiovascular events (MACEs) in a cohort with acute coronary syndromes (ACSs). A total of 1667 patien...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa025
更新日期:2020-04-15 00:00:00
abstract::Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal grow...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa006
更新日期:2020-03-27 00:00:00
abstract::Huntington's disease (HD) is caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is necessary to cause pathology and formation of HTT aggregates. Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate formation. By addressing the sufficiency questi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa001
更新日期:2020-03-13 00:00:00
abstract::Abdominal aortic aneurysm (AAA) is a major cause of sudden death in the elderly. While AAA has some overlapping genetic and environmental risk factors with atherosclerosis, there are substantial differences, and AAA-specific medication is lacking. A recent meta-analysis of genome-wide association studies has identifie...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz256
更新日期:2020-03-13 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disorder caused by mutations in the DMD gene that leads to the absence or severe reduction of dystrophin protein in muscle. The mdx mouse, also dystrophin deficient, is the model most widely used to study the pathology and test potential therapies, but the p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz266
更新日期:2020-02-01 00:00:00
abstract::Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz300
更新日期:2020-02-01 00:00:00
abstract::Mitochondria undergo continuous cycles of fusion and fission in response to physiopathological stimuli. The key player in mitochondrial fission is dynamin-related protein 1 (DRP1), a cytosolic protein encoded by dynamin 1-like (DNM1L) gene, which relocalizes to the outer mitochondrial membrane, where it assembles, oli...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz211
更新日期:2020-01-15 00:00:00
abstract::Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by mutations in the G6PC gene, encoding the catalytic subunit of glucose-6-phosphatase. Early symptoms include severe fasting intolerance, failure to thrive and hepatomegaly, biochemically associated with nonketotic hypoglycemia, fasting...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz283
更新日期:2020-01-15 00:00:00
abstract::The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz276
更新日期:2020-01-15 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::Genetic and environmental influences are thought to interact in their contribution to the etiology of major neuropsychiatric disorders. One of the best replicated findings obtained in genome-wide association studies are genetic variants in the CACNA1C gene. Here, we used our constitutive heterozygous Cacna1c rat model...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz235
更新日期:2019-12-15 00:00:00
abstract::The DUX4 transcription factor is normally expressed in the cleavage-stage embryo and regulates genes involved in embryonic genome activation. Misexpression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD). We recently showed DUX4-induced toxicity is due, in part, t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz242
更新日期:2019-12-01 00:00:00