Abstract:
:We determined the genomic structure of the human gene encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate and is the rate-limiting and major regulatory enzyme in sterol biosynthesis. The gene is more than 21 kb long, about five times the size of its corresponding cDNA. It consists of 20 exons, ranging in size from 68 to 1809bp. An amino-terminal hydrophobic membrane-bound domain is encoded by exons 2-10, a flexible linker domain by exons 10 and 11, and the catalytic domain by exons 11-20. Exons 3-7 encode a sterol-sensing domain. We compared its genomic structure in this region with the sterol-sensing domains of three related genes, sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP), Niemann-Pick type C1 protein (NPC1), and a morphogen receptor, Patched. Two of the five positions of introns in the sterol-sensing domain of the HMG-CoA reductase gene were identical to the exon/intron organization of this domain in the related human genes, but these positions of introns were not conserved in homologues from lower organisms, except in one instance. The data suggested that exon-shuffling may have occurred during relatively recent evolution: this would account for the structural similarity of this domain in four quite different human proteins.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Nakajima T,Iwaki K,Hamakubo T,Kodama T,Emi Mdoi
10.1007/s100380070017keywords:
subject
Has Abstractpub_date
2000-01-01 00:00:00pages
284-9issue
5eissn
1434-5161issn
1435-232Xjournal_volume
45pub_type
杂志文章abstract::Albright's hereditary osteodystrophy (AHO) is characterized by short stature, round face, calcifications, obesity, brachydactyly and intellectual disability. AHO without hormone resistance is called pseudopseudohypoparathyroidism (PPHP), a rare clinical condition difficult to diagnose with highly variable features. PP...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.1
更新日期:2012-04-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is caused by functional loss of the survival of motor neuron 1 (SMN1) gene. Despite genetic homogeneity, phenotypic variability indicates the involvement of disease modifiers. SMN1 is located in 5q13.2 segmental duplication, enriched in genes and prone to unequal rearrangements, which res...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.104
更新日期:2015-11-01 00:00:00
abstract::alpha-1-Antichymotrypsin (ACT) is a plasma protease inhibitor belonging to the serpine superfamily; it has many functions. and thus qualitative change in ACT is likely to result in specific diseases. We previously reported a variant AACT (ACT Isehara-1, Met389Val, A1252G) in patients with ischemic cerebrovascular dise...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170125
更新日期:2001-01-01 00:00:00
abstract::A full-length cDNA encoding a novel protein was isolated and sequenced from a human placental cDNA library. This cDNA consists of 1,735 base pairs and has a predicted open reading frame (ORF) encoding 354 amino acids. It possesses a putative signal sequence, a long extracellular domain, a transmembrane region, a short...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380070013
更新日期:2000-01-01 00:00:00
abstract::Deletion of exons 45-55 (del45-55) in the Duchenne muscular dystrophy gene (DMD) has gained particular interest in the field of molecular therapy, because it causes a milder phenotype than DMD, and therefore, may represent a good candidate for the goal of a multiple exon-skipping strategy. We have precisely characteri...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2008.8
更新日期:2009-02-01 00:00:00
abstract::Numerous CpG islands containing tissue-specific differentially methylated regions (TDMRs) are potential methylation sites in normal cells and tissues. The VASA (also known as DDX4) gene is believed to be under the control of TDMRs. A total of 131 male patients with idiopathic azoospermia or severe oligospermia were ev...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.59
更新日期:2009-08-01 00:00:00
abstract::The expansion of polyalanine repeats is known to cause at least nine disorders, including congenital central hypoventilation syndrome (CCHS). Unequal crossover has been speculated as the expanding mechanism, in contrast to strand slippage in polyglutamine expansion disorders. We carried out segregation analysis of PHO...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0197-3
更新日期:2007-01-01 00:00:00
abstract::As a result of the combination of great linguistic and cultural diversity, the highland populations of Daghestan present an excellent opportunity to test the hypothesis of language-gene coevolution at a fine geographic scale. However, previous genetic studies generally have been restricted to uniparental markers and h...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.132
更新日期:2016-03-01 00:00:00
abstract::The importance of epigenetic control in the development of the central nervous system has recently been attracting attention. Methylation patterns of lysine 4 and lysine 36 in histone H3 (H3K4 and H3K36) in the central nervous system are highly conserved among species. Numerous complications of body malformations and ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-00889-4
更新日期:2021-01-06 00:00:00
abstract::PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14 (PARK14). In addition, very recently, PLA2G6 mutations have been reported to represent a phenotype of he...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0519-7
更新日期:2019-01-01 00:00:00
abstract::GNE myopathy is a rare autosomal recessive distal myopathy caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the bi-functional enzyme critical for sialic acid biosynthesis. In this study, we summarized the clinical features, pathological characteristics, and genetic profiles ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0525-9
更新日期:2019-01-01 00:00:00
abstract::Familial recurrence of anorectal malformations (ARMs) has been reported in single institution case series and in two population-based studies. Here, we investigate the familial aggregation of ARMs using well-established, unbiased methods in a population genealogy of Utah. Study subjects included 255 ARM cases identifi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0487-y
更新日期:2018-10-01 00:00:00
abstract::There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brai...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.106
更新日期:2009-12-01 00:00:00
abstract::With congenital central hypoventilation syndrome (CCHS), most patients have a de novo 5-13 polyalanine expansion mutation in PHOX2B. We reported previously that de novo polyalanine expansion mutations were of paternal origin and were derived from unequal sister chromatid exchange during spermatogenesis in six and four...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.109
更新日期:2010-01-01 00:00:00
abstract::Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in te...
journal_title:Journal of human genetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/s10038-018-0518-8
更新日期:2018-12-01 00:00:00
abstract::Bivariate survival models with discretely distributed frailty based on the major gene concept and applied to the data on related individuals such as twins and sibs can be used to estimate the underlying hazard, the relative risk and the frequency of the longevity allele. To determine the position of the longevity gene...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.80
更新日期:2013-10-01 00:00:00
abstract::Glutathione synthetase deficiency is a rare autosomal recessive disorder resulting in low levels of glutathione and an increased susceptibility to oxidative stress. Patients with glutathione synthetase deficiency typically present in the neonatal period with hemolytic anemia, metabolic acidosis and neurological impair...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.20
更新日期:2016-07-01 00:00:00
abstract::Behçet disease (BD) is an immune-mediated disease. The cause of BD remains unknown, but the existence of multiple pathological pathways is suspected, including different genetic factors. Polymorphisms in ERAP1 gene have been associated with an increased risk of BD. However, while current BD-associated ERAP1 variants a...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0709-y
更新日期:2020-03-01 00:00:00
abstract::The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian po...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.99
更新日期:2010-11-01 00:00:00
abstract::Congenital scoliosis (CS) is a form of scoliosis caused by congenital vertebral malformations. Genetic predisposition has been demonstrated in CS. We previously reported that TBX6 loss-of-function causes CS in a compound heterozygous model; however, this model can explain only 10% of CS. Many monogenic and polygenic C...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0698-x
更新日期:2020-03-01 00:00:00
abstract::Genomic diversity based on 13 short tandem repeat (STR) loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, TH01, TPOX, and CSF1PO) is reported for the first time in Basques from the provinces of Guipúzcoa and Navarre (Spain). STR data from previous studies on Basques from Alava and Viz...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0268-2
更新日期:2005-01-01 00:00:00
abstract::Spondylo-epi-metaphyseal dysplasia (SEMD) is a group of inherited skeletal diseases characterized by the anomalies in spine, epiphyses and metaphyses. SEMD is highly heterogeneous and >20 distinct entities have been identified. Here we describe a novel type of SEMD in two unrelated Turkish patients who presented with ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2017.38
更新日期:2017-08-01 00:00:00
abstract::Ectodermal-dysplasia-syndactyly syndrome (EDSS1) is a rare form of ectodermal dysplasia (ED), affecting skin and its appendages mainly hair, teeth and nails. In the present study, we have investigated a large consanguineous Pakistani family with 10 individuals showing features of EDSS1. Human genome was screened using...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.18
更新日期:2011-05-01 00:00:00
abstract::Factors predisposing to the phenotypic features of familial combined hyperlipidemia have not been clearly defined. In the course of investigating familial coronary artery disease in Utah, we identified a three-generation family in which multiple members were affected with type IIa hyperlipoproteinemia (HLP IIa), type ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050202
更新日期:2000-01-01 00:00:00
abstract::PlexinA is a neuronal receptor protein that facilitates axon guidance during embryogenesis. This gene is associated with several neurological disorders including Alzheimer's disease, Parkinson's disease and autism. However, the effect of variants of PlexinA on brain structure remains unclear. We demonstrate that singl...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2014.107
更新日期:2015-03-01 00:00:00
abstract::Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0399-0
更新日期:2006-01-01 00:00:00
abstract::Heterozygous disruptions in FOXP1 are responsible for developmental delay, intellectual disability and speech deficit. Heterozygous germline PTCH1 disease-causing variants cause Gorlin syndrome. We describe a girl with extreme megalencephaly, developmental delay and severe intellectual disability. Dysmorphic features ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0508-x
更新日期:2018-11-01 00:00:00
abstract::To elucidate possible physiological functions of human endogenous retroviruses (HERVs) and their role in the pathogenesis of human diseases, we have developed a strategy to identify transcriptionally active HERV genes. By this approach, we have identified and isolated an active HERV-E gene that was mapped to 17q11. Al...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170012
更新日期:2001-01-01 00:00:00
abstract::Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0765-3
更新日期:2020-09-01 00:00:00
abstract::Hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) is an adult-onset peripheral neurodegenerative disorder which has been reported only in the Okinawa Islands, Japan. The disease locus of "Okinawa-type" HMSN-P has been previously mapped to 3q13.1, with all affected individuals sharing an identica...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0193-7
更新日期:2007-01-01 00:00:00