Abstract:
:Human cytidine deaminase APOBEC3G and the virion infectivity factor (vif) of the human immunodeficiency virus (HIV) are a pair of antagonistic molecules. In the absence of vif, APOBEC3G induces a high rate of dC to dU mutations in the nascent reverse transcripts of HIV that leads to the degradation of the HIV genome. HIV vif, on the other hand, can suppress the translation and trigger the degradation of human APOBEC3G. Here, we studied the rate of APOBEC3G gene evolution from five hominoids and two Old World monkeys. Averaged across the entire coding region, the rate of non-synonymous nucleotide substitutions is approximately 1.4 times the rate of synonymous substitutions, strongly suggesting that APOBEC3G has been under positive Darwinian selection. A comparison between the nucleotide polymorphisms within humans and the substitutions among the seven primates reveals a significant excess of non-synonymous substitutions. Furthermore, the rate of charge-altering non-synonymous substitution is approximately 1.8 times that of charge-conserving substitution, indicating that the selection is promoting the diversity of the protein charge profile. However, no difference in selective pressure on APOBEC3G is detected between hosts and non-hosts of HIV or simian immunodeficiency virus (SIV). These results, together with recent findings that the antiviral activity of APOBEC3G is not limited to HIV/SIV, suggest that the selective pressure on APOBEC3G is not solely from HIV/SIV and that APOBEC3G is a broad antiviral enzyme. The identification of pervasive positive selection for charge-altering amino acid substitutions supports the hypothesis of electrostatic interactions between APOBEC3G and vif or its functional equivalents.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Zhang J,Webb DMdoi
10.1093/hmg/ddh183subject
Has Abstractpub_date
2004-08-15 00:00:00pages
1785-91issue
16eissn
0964-6906issn
1460-2083pii
ddh183journal_volume
13pub_type
杂志文章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::Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in Lesch-Nyhan disease (LND), where affected individuals exhibit a characteristic neurobehavioral disorder that has been linked with dysfunction of dopaminergic pathways of the basal ganglia. Since the functions of HPRT, a housekeeping enzyme res...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp164
更新日期:2009-07-01 00:00:00
abstract::A family of growth arrest specific (Gas) genes was operationally defined on the basis of the strategy utilized to isolate them e.g. differential expression in quiescent and growing cells. Our interest in the Gas-3 gene was prompted by our previously reported localization of the gene on the mouse chromosome 11.44 +/- 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.5.331
更新日期:1992-08-01 00:00:00
abstract::Circletail is one of only two mouse mutants that exhibit the most severe form of neural tube defect (NTD), termed craniorachischisis. In this disorder, almost the entire brain and spinal cord is affected, owing to a failure to initiate neural tube closure. Craniorachischisis is a significant cause of lethality in huma...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg014
更新日期:2003-01-15 00:00:00
abstract::Heterozygosity for mutations (N88S and P90L) in the N-glycosylation site of seipin/BSCL2 is associated with the autosomal dominant motor neuron diseases, spastic paraplegia 17 and distal hereditary motor neuropathy type V, referred to as 'seipinopathies'. Previous in vitro studies have shown that seipinopathy-linked m...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr304
更新日期:2011-10-01 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::Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ∼40% of patients. We hypothesized that unexplained IS cases represent a large collection of rare single-gene disorders. We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n = 44) ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu199
更新日期:2014-09-15 00:00:00
abstract::Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal reces...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr063
更新日期:2011-05-01 00:00:00
abstract::Junctional epidermolysis bullosa inversa is an autosomal recessive blistering skin disease with an ultrastructural hemidesmosome defect similar to that of the Herlitz disease, yet with a non-lethal and different course of the disease. Its delineation is based on five geographically associated Norwegian families where ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.8.1387
更新日期:1994-08-01 00:00:00
abstract::The genomic instability of persons with Bloom's syndrome (BS) features particularly an increased number of sister-chromatid exchanges (SCEs). The primary cause of the genomic instability is mutation at BLM, which encodes a DNA helicase of the RecQ family. BLM interacts with Topoisomerase IIIalpha (Topo IIIalpha), and ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.12.1287
更新日期:2001-06-01 00:00:00
abstract::Amelogenesis imperfecta (AI), is an inherited odontological disease which affects the formation of enamel. We report a linkage analysis study performed on three Swedish families, where the affected members had an autosomal dominant variant of AI (ADAI) clinically characterized as local hypoplastic. Significant linkage...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.9.1621
更新日期:1994-09-01 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::To elucidate the molecular mechanisms of impaired elastic fiber formation in recessive cutis laxa, we have investigated two disease-causing missense substitutions in fibulin-5, C217R and S227P. Pulse-chase immunoprecipitation experiments indicated that S227P mutant fibulin-5 was synthesized and secreted by skin fibrob...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl414
更新日期:2006-12-01 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of ...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddi230
更新日期:2005-08-01 00:00:00
abstract::Galphaq, encoded by the human GNAQ gene, is an effector subunit of the Gq heterotrimeric G-protein and the convergence point for signaling of multiple Gq-coupled neurohormonal receptors. To identify naturally occurring mutations that could modify GNAQ transcription, we examined genomic DNA isolated from 355 normal sub...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm229
更新日期:2007-11-15 00:00:00
abstract::Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive deaf-blinding disorders. Pathophysiology leading to the blinding retinal degeneration in USH is uncertain. There is evidence for involvement of the photoreceptor cilium, photoreceptor synapse, the adjacent retinal pigment epithelium (RPE)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn140
更新日期:2008-08-01 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::Subcortical band heterotopia (SBH) are bilateral and symmetric ribbons of gray matter found in the central white matter between the cortex and the ventricular surface, which comprises the less severe end of the lissencephaly (agyria-pachygyria-band) spectrum of malformations. Mutations in DCX (also known as XLIS ) hav...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.9.1757
更新日期:1999-09-01 00:00:00
abstract::We report identification of a novel genetic locus (GLC1P) for normal tension glaucoma (NTG) on chromosome 12q14 using linkage studies of an African-American pedigree (maximum non-parametric linkage score = 19.7, max LOD score = 2.7). Subsequent comparative genomic hybridization and quantitative polymerase chain reacti...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr123
更新日期:2011-06-15 00:00:00
abstract::Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially tre...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw361
更新日期:2016-12-15 00:00:00
abstract::Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of mi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy008
更新日期:2018-03-01 00:00:00
abstract::F1Fo-ATP synthase is a key enzyme of mitochondrial energy provision producing most of cellular ATP. So far, mitochondrial diseases caused by isolated disorders of the ATP synthase have been shown to result from mutations in mtDNA genes for the subunits ATP6 and ATP8 or in nuclear genes encoding the biogenesis factors ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq254
更新日期:2010-09-01 00:00:00
abstract::NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr214
更新日期:2011-08-15 00:00:00
abstract::Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl439
更新日期:2007-01-01 00:00:00
abstract::Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among the most common motor neuron diseases to afflict the human population. A deficiency of the survival of motor neuron (SMN) protein causes SMA and is also reported to be an exacerbating factor in the development of ALS. However, pathways lin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds174
更新日期:2012-08-01 00:00:00
abstract::The Smith-Lemli-Opitz syndrome (SLOS; also known as the RSH syndrome) is an autosomal recessive genetic disorder, leading to characteristic multi-organ developmental abnormalities, dysmorphic facies, limb malformations and mental retardation. Mutations in the gene for Delta(7)-dehydrocholesterol reductase (Delta(7)-re...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.9.1385
更新日期:2000-05-22 00:00:00
abstract::It is now well established that the genomic landscape of DNA methylation (DNAm) gets altered as a function of age, a process we here call 'epigenetic drift'. The biological, functional, clinical and evolutionary significance of this epigenetic drift, however, remains unclear. We here provide a brief review of epigenet...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt375
更新日期:2013-10-15 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::Migraine is a prevalent, debilitating and costly disorder with an ongoing unmet medical need. Human genetic studies have provided considerable insights into the molecular underpinnings of this complex brain disorder. Classical linkage studies have revealed the causes of familial hemiplegic migraine, while more recentl...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt364
更新日期:2013-10-15 00:00:00