Abstract:
:The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements (sublimons) has been proposed as a potential contributor to aging, and also to diseases such as cardiomyopathy or coronary heart disease. Tissue-specific sublimons, varying in abundance by three orders of magnitude between individuals, have recently been observed in myocardium of control subjects. To study the relationship between myocardial sublimon levels and various types of cardiac disease and aging, we applied a semi-quantitative fluorescent PCR assay on cellular DNA extracted from left ventricle in a series of 300 well characterized male victims of sudden death up to age 70 (Helsinki Sudden Death Study). The most prevalent classes of sublimons were present at <0.1 to 91 copies per cell, but their abundance did not correlate with any cardiac disease phenotype. In multiple regression analyses age (beta = 0.43, P < 0.0001) and smoking (bet = 0.25, P = 0.012) were the only independent factors found to correlate with sublimon levels. Thus, sublimons are inferred to accumulate with age in myocardium of a subset of individuals, but to levels where they do not appear to have any phenotypic effects during a typical life span. We propose that, instead of being a causal factor in cardiac aging, sublimons co-exist with wild-type mtDNA in an equilibrium which is regulated by as yet unknown mechanisms.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Kajander OA,Karhunen PJ,Jacobs HTdoi
10.1093/hmg/11.3.317subject
Has Abstractpub_date
2002-02-01 00:00:00pages
317-24issue
3eissn
0964-6906issn
1460-2083journal_volume
11pub_type
杂志文章abstract::We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a min...
journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
doi:10.1093/hmg/ddt403
更新日期:2014-01-01 00:00:00
abstract::The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression pro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr328
更新日期:2011-10-15 00:00:00
abstract::Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into saposin B's physiological functions, a specific...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn135
更新日期:2008-08-01 00:00:00
abstract::Poly(ADP-ribose) polymerase 2 (PARP-2) is a newly discovered member of the PARP family. We report the association of PARP-2 with mammalian centromeres in a cell-cycle-dependent manner, accumulating at centromeres during prometaphase and metaphase, disassociating during anaphase, and disappearing from the centromeres b...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.19.2319
更新日期:2002-09-15 00:00:00
abstract::Four naturally occurring sequence variations have been found in the coding region of the DYT1 gene encoding torsinA. One of these, a 3 bp (DeltaGAG) deletion, underlies dominantly inherited cases of early-onset torsion dystonia. Others, including a single nucleotide polymorphism that replaces aspartic acid (D) at resi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl055
更新日期:2006-04-15 00:00:00
abstract::Adolescent idiopathic scoliosis (AIS) is a complex inherited spinal deformity whose etiology has been elusive. While common genetic variants are associated with AIS, they explain only a small portion of disease risk. To explore the role of rare variants in AIS susceptibility, exome sequence data of 391 severe AIS case...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv463
更新日期:2016-01-01 00:00:00
abstract::We describe and functionally characterize six mutations of the acetylcholine receptor (AChR) epsilon subunit gene in three congenital myasthenic syndrome patients. Endplate studies demonstrated severe endplate AChR deficiency, dispersed endplate regions and well preserved junctional folds in all three patients. Electr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.5.753
更新日期:1997-05-01 00:00:00
abstract::Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv183
更新日期:2015-08-15 00:00:00
abstract::We have studied 21 families with Wilson disease (WND), using restriction fragment length polymorphisms (RFLPs) in the 13q14.3 region, to measure linkage of these markers to the disease locus. In addition to previously described markers, we include linkage data for a newly isolated marker (D13S86) and an established ma...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.9.1401
更新日期:1993-09-01 00:00:00
abstract::Single nucleotide polymorphisms (SNPs) that alter exon splicing efficiency are an emerging class of functional genetic variants. Since mutations in low-density lipoprotein receptor (LDLR) are a primary cause of familial hypercholesterolemia, we evaluated whether LDLR SNPs may alter splicing efficiency and cholesterol ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm124
更新日期:2007-07-15 00:00:00
abstract::Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv358
更新日期:2015-11-15 00:00:00
abstract::Synapsin I (SynI) is a synaptic vesicle (SV) phosphoprotein playing multiple roles in synaptic transmission and plasticity by differentially affecting crucial steps of SV trafficking in excitatory and inhibitory synapses. SynI knockout (KO) mice are epileptic, and nonsense and missense mutations in the human SYN1 gene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt071
更新日期:2013-06-01 00:00:00
abstract::What would define real progress in the field of deafness research in fundamental and medical terms? In fundamental terms, progress would be measured by an improvement in our knowledge of the development and physiology of the ear. In medical terms, progress would lead to the division of the broad category of hearing de...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/7.10.1589
更新日期:1998-01-01 00:00:00
abstract::Autosomal nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by mutations in the Aquaporin-2 (AQP2) gene. Analysis of a new family with dominant NDI revealed a single nucleotide deletion (727deltaG) in one AQP2 allele, which encoded ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.7.779
更新日期:2002-04-01 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::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::Three distinct regions, designated AZFa, b and c from proximal to distal Yq, are required for normal spermato-genesis in humans. Deletions involving AZFa (deletion interval 5C/D) seem to occur less frequently in infertile men and to be associated with a more severe testicular phenotype, with almost complete absence of...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.8.1161
更新日期:2000-05-01 00:00:00
abstract::DNA methylation (DNAm) has been linked to changes in chromatin structure, gene expression and disease. The DNAm level can be affected by genetic variation; although, how this differs by CpG dinucleotide density and genic location of the DNAm site is not well understood. Moreover, the effect of disease causing variants...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw072
更新日期:2016-06-15 00:00:00
abstract::Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx239
更新日期:2017-09-15 00:00:00
abstract::First- and second-generation sequencing technologies have led the way in revolutionizing the field of genomics and beyond, motivating an astonishing number of scientific advances, including enabling a more complete understanding of whole genome sequences and the information encoded therein, a more complete characteriz...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddq416
更新日期:2010-10-15 00:00:00
abstract::Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq506
更新日期:2011-02-01 00:00:00
abstract::Apolipoprotein-E (apoE) protects against coronary artery disease via hepatic removal of atherogenic remnant lipoproteins, sequestration of cholesterol from vessel walls and local anti-oxidant, anti-platelet and anti-inflammatory actions. ApoE gene transfer may thus ameliorate a hyperlipidaemic profile and have benefic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.17.2545
更新日期:2000-10-12 00:00:00
abstract::Mutations in the human RPGR gene cause one of the most common and severe forms of inherited retinal dystrophy, but the function of its protein product remains unclear. We have identified two genes resembling human RPGR (ZFRPGR1, ZFRPGR2) in zebrafish (Danio rerio), both of which are expressed within the nascent and ad...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp533
更新日期:2010-02-15 00:00:00
abstract::Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn106
更新日期:2008-07-15 00:00:00
abstract::X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency resulting from mutations in the gene for a cytoplasmic protein tyrosine kinase (Btk). We have utilised reverse-transcription-based PCR in combination with the chemical cleavage and mismatch technique (CCM) to screen for Btk mutations in 42 unrelated p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.693
更新日期:1995-04-01 00:00:00
abstract::Although the varepsilon4 allele of the apolipoprotein E gene appears as an important biological marker for Alzheimer's disease (AD) susceptibility, other genetic determinants are clearly implicated in the AD process. Here, we propose that a genetic variation in the transcriptional factor LBP-1c/CP2/LSF gene, located c...
journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
doi:10.1093/oxfordjournals.hmg.a018918
更新日期:2000-09-22 00:00:00
abstract::Uterine leiomyomata (UL), also known as fibroids, are the most common pelvic tumors in women of reproductive age and are the primary indication for hysterectomy in the USA. Many lines of evidence indicate a strong genetic component to the development of these tumors. In fact, approximately 40% of UL have non-random, t...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm043
更新日期:2007-04-15 00:00:00
abstract::Chediak-Higashi syndrome is an autosomal recessive, immune deficiency disorder of human (CHS) and mouse (beige, bg) that is characterized by abnormal intracellular protein transport to, and from, the lysosome. Recent reports have described the identification of homologous genes that are mutated in human CHS and bg mic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1091
更新日期:1997-07-01 00:00:00
abstract::The striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin, a giant molecule that contains several immunoglobulin (Ig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.7.1329
更新日期:1999-07-01 00:00:00
abstract::The transcription factor SOX10 is mutated in the human neurocristopathy Waardenburg-Shah syndrome (WS4), which is characterized by enteric aganglionosis and pigmentation defects. SOX10 directly regulates genes expressed in neural crest lineages, including the enteric ganglia and melanocytes. Although some SOX10 target...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi442
更新日期:2006-01-15 00:00:00