Abstract:
:The APOE epsilon4 allele is a strong genetic susceptibility factor for Alzheimer's disease. Interaction with other biological factors may modulate the effect of the apoE isoforms. However, previous work suggested that other genetic variability within the APOE locus, influencing the effect of the epsilon4 allele, may exist. Such variability could modify the expression of the APOE gene and, in particular, the level of expression of APOE alleles could be an important determinant of disease pathogenesis. To test this hypothesis we examined the levels of expression of APOE in heterozygotes with AD and in controls, using a new method of semi-quantitation. We report that relative epsilon4 mRNA expression is increased in AD compared with controls and suggest that genetic variability in the neural expression of APOE contributes to disease risk.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Lambert JC,Pérez-Tur J,Dupire MJ,Galasko D,Mann D,Amouyel P,Hardy J,Delacourte A,Chartier-Harlin MCdoi
10.1093/hmg/6.12.2151subject
Has Abstractpub_date
1997-11-01 00:00:00pages
2151-4issue
12eissn
0964-6906issn
1460-2083pii
dda266journal_volume
6pub_type
杂志文章abstract::The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chines...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw346
更新日期:2016-12-15 00:00:00
abstract::Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome in which affected individuals have a greatly increased predisposition to the development of haemangioblastomas of the central nervous system and retina, renal cell carcinoma and phaeochromocytoma. The VHL gene has been mapped to chromos...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.879
更新日期:1993-07-01 00:00:00
abstract::Mutations in the DFNB31 gene encoding the PDZ scaffold protein whirlin are causative for hearing loss in man and mouse. Whirlin is known to be essential for the elongation process of the stereocilia of sensory hair cells in the inner ear, though its complete spatial and temporal expression patterns remained elusive. H...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi490
更新日期:2006-03-01 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
abstract::Mutations in the gene encoding the inner nuclear membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk the Nucleoskeleton with the Cytoskeleton...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn386
更新日期:2009-02-15 00:00:00
abstract::Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, B...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu250
更新日期:2014-10-15 00:00:00
abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major path...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx214
更新日期:2017-09-01 00:00:00
abstract::Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu190
更新日期:2014-09-15 00:00:00
abstract::Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associated with cardiomyopathy, is caused by severely reduced frataxin, a mitochondrial protein involved in Fe-S cluster assembly. We have recently generated mouse models that reproduce important progressive pathological and biochemical features of the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh114
更新日期:2004-05-15 00:00:00
abstract::Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.13.2247
更新日期:1997-12-01 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
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::We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome region...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.17.1987
更新日期:2002-08-15 00:00:00
abstract::GM2 gangliosidoses are a group of lysosomal storage disorders which include Sandhoff disease and Tay-Sachs disease. Dysregulation of glutamate receptors has been recently postulated in the pathology of Sandhoff disease. Glutamate receptor association with neuronal pentraxins 1 and 2, and the neuronal pentraxin recepto...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw422
更新日期:2017-02-15 00:00:00
abstract::Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1021
更新日期:1997-07-01 00:00:00
abstract::Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alph...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.11.1733
更新日期:1996-11-01 00:00:00
abstract::Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddr270
更新日期:2011-09-15 00:00:00
abstract::In our efforts to identify new loci responsible for non-syndromic autosomal recessive forms of deafness, DFNB loci, we have pursued the analysis of large consanguineous affected families living in geographically isolated areas. Here, we report on the study of a Lebanese family comprising nine members presenting with a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.3.409
更新日期:1999-03-01 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::Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and bet...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.9.1379
更新日期:1998-09-01 00:00:00
abstract::Polyglutamine expansions in the huntingtin gene cause Huntington's disease (HD). Huntingtin is ubiquitously expressed, leading to pathological alterations also in peripheral organs. Variations in the length of the polyglutamine tract explain up to 70% of the age-at-onset variance, with the rest of the variance attribu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy077
更新日期:2018-05-15 00:00:00
abstract::Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), characterized by microcephaly, chromosomal instability, radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin; however, 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi482
更新日期:2006-03-01 00:00:00
abstract::A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha-synuclein gene were amplified by PCR from i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.4.751
更新日期:1998-04-01 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::While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.3.501
更新日期:1998-03-01 00:00:00
abstract::Cystathionine beta-synthase (CBS) deficiency is the major cause of homocystinuria in humans. The most frequent symptoms of homocystinuria include: dislocated optic lenses, vascular disorders, skeletal abnormalities and mental retardation. Patients with this deficiency have elevated levels of homocyst(e)ine, methionine...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.10.1633
更新日期:1993-10-01 00:00:00
abstract::To determine factors governing triplet repeat expansion at FMR1, we need to understand the basis of normal variation. We have sequenced the FMR1 repeat from 102 normal X chromosomes and show that most are interrupted with a regularly spaced AGG trinucleotide giving an ordered structure to the array. Five types of arra...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.9.1553
更新日期:1994-09-01 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::To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.6.387
更新日期:1992-09-01 00:00:00
abstract::Autism is a heterogeneous condition that is likely to result from the combined effects of multiple genetic factors interacting with environmental factors. Given its complexity, the study of autism associated with Mendelian single gene disorders or known chromosomal etiologies provides an important perspective. We used...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm116
更新日期:2007-07-15 00:00:00