Abstract:
:According to the telomere hypothesis of senescence, the progressive shortening of telomeres that occurs upon division of normal somatic cells eventually leads to cellular senescence. The immortalisation of human cells is associated with the acquisition of a telomere maintenance mechanism which is usually dependent upon expression of the enzyme telomerase. About one third of in vitro immortalised human cell lines, however, have no detectable telomerase but contain telomeres that are abnormally long. The nature of the alternative telomere maintenance mechanism (referred to as ALT, for Alternative Lengthening of Telomeres) that must exist in these telomerase-negative cells has not been elucidated. It has previously been shown that abnormal lengthening of yeast telomeres may occur due to mutations in the yeast telomerase RNA gene. That this is not the mechanism of the abnormally long telomeres in ALT cell lines was demonstrated by the finding that seven of seven ALT lines have wild-type human telomerase RNA (hTR) sequence, including a novel polymorphism that is present in 30% of normal individuals. We found that two ALT cell lines have no detectable expression of the hTR gene. This shows that the ALT mechanism in these cell lines is not dependent on hTR. Expression of exogenous hTR via infection of these cells with a recombinant hTR-adenovirus vector did not result in telomerase activity, indicating that their lack of telomerase activity is not due to absence of hTR expression. We conclude that the ALT mechanism is not dependent on the expression of hTR, and does not involve mutations in the hTR sequence.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Bryan TM,Marusic L,Bacchetti S,Namba M,Reddel RRdoi
10.1093/hmg/6.6.921subject
Has Abstractpub_date
1997-06-01 00:00:00pages
921-6issue
6eissn
0964-6906issn
1460-2083pii
dda125journal_volume
6pub_type
杂志文章abstract::Multicentric chromosomes are often found in tumor cells and certain cell lines. How they are generated is not fully understood, though their stability suggests that they are non-functional during chromosome segregation. Growing evidence has implicated microtubule motor proteins in attachment of chromosomes to the mito...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.4.671
更新日期:1998-04-01 00:00:00
abstract::Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv124
更新日期:2015-07-01 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::Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder phenotypically characterized by many features of premature aging. Most cases of HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre-mRNA and l...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr385
更新日期:2011-12-01 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::The widespread use of persistent organic polybrominated diphenyl ethers (PBDEs) as commercial flame retardants has raised concern about potential long-lived effects on human health. Epigenetic mechanisms, such as DNA methylation, are responsive to environmental influences and have long-lasting consequences. Autism spe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds046
更新日期:2012-06-01 00:00:00
abstract::Mutations in GDAP1 lead to recessively or dominantly inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT), indicating that GDAP1 is essential for the viability of cells in the peripheral nervous system. GDAP1 contains domains characteristic of glutathione-S-transferases (GSTs), is located in the outer ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr450
更新日期:2012-01-01 00:00:00
abstract::Craniosynostosis, the abnormal development of the calvarial sutures, occurs as an autosomal dominant trait in many clinically distinct syndromes. We performed linkage analysis of a provisionally novel type of autosomal dominant craniosynostosis in a large three generational family. Linkage was established between the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.2.119
更新日期:1993-02-01 00:00:00
abstract::A long-standing question concerning X-chromosome inactivation (XCI) has been how some genes avoid the otherwise stable chromosome-wide heterochromatinization of the inactive X chromosome. As 20% or more of human X-linked genes escape from inactivation, such genes are an important contributor to sex differences in gene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy039
更新日期:2018-04-01 00:00:00
abstract::Many congenital myasthenic syndromes (CMS) are associated with mutations in the genes encoding the acetylcholine receptor (AChR), an oligomeric protein with the structure alpha(2)betadelta epsilon. AChR deficiency is frequently due to homozygous or heteroallelic mutations in the AChR epsilon subunit, most of which cau...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.24.3087
更新日期:2002-11-15 00:00:00
abstract::The breast cancer gene, BRCA2, is essential for viability, yet patients with Fanconi anemia-D1 subtype are born alive with biallelic mutations in this gene. The hypomorphic nature of the mutations is believed to support viability, but this is not always apparent. One such mutation is IVS7+2T>G, which causes premature ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw066
更新日期:2016-05-15 00:00:00
abstract::Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv637
更新日期:2016-03-01 00:00:00
abstract::Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu511
更新日期:2015-02-15 00:00:00
abstract::NSDHL, for NAD(P)H steroid dehydrogenase-like, encodes a sterol dehydrogenase or decarboxylase involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis. Mutations in this gene are associated with human CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and li...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg321
更新日期:2003-11-15 00:00:00
abstract::The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw383
更新日期:2017-01-15 00:00:00
abstract::Somatic and germline mutations in PTEN (phosphatase and tensin homolog deleted on chromosome 10) are found in sporadic cancers and Cowden syndrome patients, respectively. Recent identification of naturally occurring cancer and germline mutations within the ATP-binding motifs of PTEN (heretofore referred to as PTEN ATP...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq434
更新日期:2011-01-01 00:00:00
abstract::Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw233
更新日期:2016-09-15 00:00:00
abstract::Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Different hypotheses exist about the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy083
更新日期:2018-05-15 00:00:00
abstract::Imputation is commonly used in genome-wide association studies to expand the set of genetic variants available for analysis. Larger and more diverse reference panels, such as the final Phase 3 of the 1000 Genomes Project, hold promise for improving imputation accuracy in genetically diverse populations such as Hispani...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw174
更新日期:2016-08-01 00:00:00
abstract::Peroxisome proliferator-activated receptors (PPARs) are ligand-mediated transcription factors, which control both lipid and energy metabolism and inflammation pathways. PPARγ agonists are effective in the treatment of metabolic diseases and, more recently, neurodegenerative diseases, in which they show promising neuro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds355
更新日期:2012-12-01 00:00:00
abstract::Monozygotic twin and other epidemiologic studies indicate that epigenetic processes may play an important role in the pathogenesis of inflammatory bowel diseases that commonly affect the colonic mucosa. The peak onset of these disorders in young adulthood suggests that epigenetic changes normally occurring in the colo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq095
更新日期:2010-06-01 00:00:00
abstract::The X-linked reproductive homeobox (RHOX) gene cluster encodes transcription factors preferentially expressed in reproductive tissues. This gene cluster has important roles in male fertility based on phenotypic defects of Rhox-mutant mice and the finding that aberrant RHOX promoter methylation is strongly associated w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw313
更新日期:2016-11-15 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) are two neurodegenerative disorders characterized by the accumulation of TDP-43. TDP-43 is proteolitically cleaved to generate two major C-terminal fragments of 35 and 25 kDa. The latter, known as TDP-25, is a consistent feature of FT...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv193
更新日期:2015-08-15 00:00:00
abstract::The apolipoprotein A5 gene (APOA5 ) has been shown to play an important role in determining plasma triglyceride concentrations in humans. We describe here a novel variant, c.553G>T, in the apolipoprotein A5 gene that is associated with hypertriglyceridemia. In contrast to some other polymorphisms, which occur in non-c...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg255
更新日期:2003-10-01 00:00:00
abstract::Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor homology domain repeat A of the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts recycling of the internalized LDLR. As a consequence, the LDLR is rerouted to the lysosomes for degradation. Although PCSK9...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr578
更新日期:2012-03-15 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::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
abstract::Linkage, association and postmortem studies have implicated regulator of G-protein signaling 4 (RGS4), which negatively modulates signal transduction at G-protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC), between...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl222
更新日期:2006-09-15 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::Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA repair pathway. To understand the role of this ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds211
更新日期:2012-09-01 00:00:00