当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > A non-coding genetic variant associated with abdominal aortic aneurysm alters ERG gene regulation.

A non-coding genetic variant associated with abdominal aortic aneurysm alters ERG gene regulation.

Abstract：

:Abdominal aortic aneurysm (AAA) is a major cause of sudden death in the elderly. While AAA has some overlapping genetic and environmental risk factors with atherosclerosis, there are substantial differences, and AAA-specific medication is lacking. A recent meta-analysis of genome-wide association studies has identified four novel single-nucleotide polymorphisms (SNPs) specifically associated with AAA. Here, we investigated the gene regulatory function for one of four non-coding SNPs associated with AAA, rs2836411, which is located in an intron of the ERG gene. Rs2836411 resides within a >70 kb super-enhancer that has high levels of H3K27ac and H3K4me1 in vascular endothelial and haematopoietic cell types. Enhancer luciferase assays in cell lines showed that the risk allele significantly alters enhancer activity. The risk allele also correlates with reduced ERG expression in aortic and other vascular tissues. To identify whether rs2836411 directly contacts the promoters of ERG and/or of genes further away, we performed allele-specific circular chromosome conformation capture sequencing. In vascular endothelial cells, which express ERG, the SNP region interacts highly within the super-enhancer, while in vascular smooth muscle cells, which do not express ERG, the interactions are distributed across a wider region that includes neighbouring genes. Furthermore, the risk allele has fewer interactions within the super-enhancer compared to the protective allele. In conclusion, our results indicate that rs2836411 likely affects ERG expression by altering enhancer activity and changing local chromatin interactions. ERG is involved in vascular development, angiogenesis, and inflammation in atherosclerosis; therefore mechanistically, rs2836411 could contribute to AAA by modulating ERG levels.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Marsman J,Gimenez G,Day RC,Horsfield JA,Jones GT

doi

10.1093/hmg/ddz256

subject

Has Abstract

pub_date

2020-03-13 00:00:00

pages

554-565

issue

4

eissn

0964-6906

issn

1460-2083

pii

5613693

journal_volume

29

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Lambda CM8, a human sequence with putative centromeric function, does not map to the centromere but is present in one to two copies at 9qter.

    abstract：:A DNA fragment isolated from a human genomic library, was reported to be present at all human centromeres and present at 16-32 copies per genome. Reintroduction of this DNA into mammalian cells as a concatenated phage clone gave rise to dicentric chromosomes which gave rise to a new, stable, chromosome. Taken together...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/1.9.749

    authors： McGill NI,Fantes J,Cooke H

    更新日期：1992-12-01 00:00:00

  • Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model.

    abstract：:Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile m...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv336

    authors： Cook C,Kang SS,Carlomagno Y,Lin WL,Yue M,Kurti A,Shinohara M,Jansen-West K,Perkerson E,Castanedes-Casey M,Rousseau L,Phillips V,Bu G,Dickson DW,Petrucelli L,Fryer JD

    更新日期：2015-11-01 00:00:00

  • Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia.

    abstract：:Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.5.669

    authors： Pulkkinen L,Kimonis VE,Xu Y,Spanou EN,McLean WH,Uitto J

    更新日期：1997-05-01 00:00:00

  • A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations.

    abstract：:Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 5-10% of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vacc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt586

    authors： Pan L,Zhang L,Zhang W,Wu X,Li Y,Yan B,Zhu X,Liu X,Yang C,Xu J,Zhou G,Xu A,Li H,Liu Y

    更新日期：2014-04-15 00:00:00

  • Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH.

    abstract：:Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair and also associated with various systemic symptoms. Approximately half of TTD patients exhibit photosensitivity, resulting from the defect in the nucleotide excision repair. Photosensitive TTD is due to mutations in three ge...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddp390

    authors： Hashimoto S,Egly JM

    更新日期：2009-10-15 00:00:00

  • Reduced protein turnover mediates functional deficits in transgenic mice expressing the 25 kDa C-terminal fragment of TDP-43.

    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

    authors： Caccamo A,Shaw DM,Guarino F,Messina A,Walker AW,Oddo S

    更新日期：2015-08-15 00:00:00

  • Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families.

    abstract：:Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg270

    authors： Pankratz N,Nichols WC,Uniacke SK,Halter C,Murrell J,Rudolph A,Shults CW,Conneally PM,Foroud T,Parkinson Study Group.

    更新日期：2003-10-15 00:00:00

  • Calcium dynamics change in degenerating cone photoreceptors.

    abstract：:Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies sugg...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw219

    authors： Kulkarni M,Trifunović D,Schubert T,Euler T,Paquet-Durand F

    更新日期：2016-09-01 00:00:00

  • An evolutionarily conserved germ cell-specific hnRNP is encoded by a retrotransposed gene.

    abstract：:The gene encoding heterogeneous ribonucleoprotein (hnRNP) G recently has been mapped to the X chromosome. All mammals have a Y chromosome-encoded homologue of HNRNP G called RBMY, which is implicated with a role in male fertility and is a candidate for the azoospermia factor gene. We have identified a new member of th...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.14.2117

    authors： Elliott DJ,Venables JP,Newton CS,Lawson D,Boyle S,Eperon IC,Cooke HJ

    更新日期：2000-09-01 00:00:00

  • Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL.

    abstract：:The infantile neuronal ceroid lipofuscinosis (INCL), a rare (one in 100 000 births) but one of the most lethal inherited neurodegenerative storage disorders of childhood, is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in s-acylated (palmitoylate...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl078

    authors： Kim SJ,Zhang Z,Lee YC,Mukherjee AB

    更新日期：2006-05-15 00:00:00

  • Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy.

    abstract：:Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. SPTLC1 encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in SPTLC1 cause...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi380

    authors： McCampbell A,Truong D,Broom DC,Allchorne A,Gable K,Cutler RG,Mattson MP,Woolf CJ,Frosch MP,Harmon JM,Dunn TM,Brown RH Jr

    更新日期：2005-11-15 00:00:00

  • Identification of consensus motifs associated with mitotic recombination and clinical characteristics in patients with paternal uniparental isodisomy of chromosome 11.

    abstract：:Uniparental disomy (UPD) is defined as the inheritance of both homologs of a given genomic region from only one parent. The majority of UPD includes an entire chromosome. However, the extent of UPD is sometimes limited to a subchromosomal region (segmental UPD). Mosaic paternal UPD (pUPD) of chromosome 11 is found in ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw023

    authors： Ohtsuka Y,Higashimoto K,Oka T,Yatsuki H,Jozaki K,Maeda T,Kawahara K,Hamasaki Y,Matsuo M,Nishioka K,Joh K,Mukai T,Soejima H

    更新日期：2016-04-01 00:00:00

  • Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.

    abstract：:Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common form of genetic hearing loss. Previous studies defined at least 15 human NSRD loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome 13, accounts for approximately 80% of cases in the Mediterranean area. Further...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.9.1605

    authors： Zelante L,Gasparini P,Estivill X,Melchionda S,D'Agruma L,Govea N,Milá M,Monica MD,Lutfi J,Shohat M,Mansfield E,Delgrosso K,Rappaport E,Surrey S,Fortina P

    更新日期：1997-09-01 00:00:00

  • Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

    abstract：:Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.9.1283

    authors： Sukegawa K,Nakamura H,Kato Z,Tomatsu S,Montaño AM,Fukao T,Toietta G,Tortora P,Orii T,Kondo N

    更新日期：2000-05-22 00:00:00

  • Defective glucocorticoid hormone receptor signaling leads to increased stress and anxiety in a mouse model of Angelman syndrome.

    abstract：:Angelman syndrome (AS) is a neurodevelopmental disorder caused due to deletions or loss-of-function mutations in maternally inherited UBE3A. Ube3a functions as an ubiquitin ligase as well as a transcriptional coactivator of steroid hormone receptors. However, the mechanisms by which maternal Ube3a deficiency gives ris...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr614

    authors： Godavarthi SK,Dey P,Maheshwari M,Jana NR

    更新日期：2012-04-15 00:00:00

  • Protein kinase C gamma, a protein causative for dominant ataxia, negatively regulates nuclear import of recessive-ataxia-related aprataxin.

    abstract：:Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disease caused by mutations in the gene encoding protein kinase C gamma (PKC gamma). We report an SCA14 family with a novel deletion of a termination-codon-containing region, resulting in a missense change and a C-terminal 13-amino-acid extension with inc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp298

    authors： Asai H,Hirano M,Shimada K,Kiriyama T,Furiya Y,Ikeda M,Iwamoto T,Mori T,Nishinaka K,Konishi N,Udaka F,Ueno S

    更新日期：2009-10-01 00:00:00

  • Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease.

    abstract：:Hirschsprung disease (HSCR) is a frequent neurocristopathy characterized by the absence of submucosal and myenteric plexuses in a variable length of the gastrointestinal tract. Pedigrees and segregation analyses suggested the involvement of one or several dominant genes with low penetrance in HSCR. Considering that RE...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.9.1449

    authors： Doray B,Salomon R,Amiel J,Pelet A,Touraine R,Billaud M,Attié T,Bachy B,Munnich A,Lyonnet S

    更新日期：1998-09-01 00:00:00

  • Low-frequency germline variants across 6p22.2-6p21.33 are associated with non-obstructive azoospermia in Han Chinese men.

    abstract：:Genome-wide association studies (GWAS) have identified several common loci contributing to non-obstructive azoospermia (NOA). However, a substantial fraction of NOA heritability remains undefined, especially those low-frequency [defined here as having a minor allele frequency (MAF) between 0.5 and 5%] and rare (MAF be...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv257

    authors： Ni B,Lin Y,Sun L,Zhu M,Li Z,Wang H,Yu J,Guo X,Zuo X,Dong J,Xia Y,Wen Y,Wu H,Li H,Zhu Y,Ping P,Chen X,Dai J,Jiang Y,Xu P,Du Q,Yao B,Weng N,Lu H,Wang Z,Zhu X,Yang X,Xiong C,Ma H,Jin G,Xu J,Wang

    更新日期：2015-10-01 00:00:00

  • The fundamental and medical impacts of recent progress in research on hereditary hearing loss.

    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

    authors： Kalatzis V,Petit C

    更新日期：1998-01-01 00:00:00

  • PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations.

    abstract：:We have studied the functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. Surprisingly, these cells had an efficient oxidative phosphorylation (OXPHOS); however, when mitochondria from these cells were transferred to an osteosarcoma nuclear backgr...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm045

    authors： Srivastava S,Barrett JN,Moraes CT

    更新日期：2007-04-15 00:00:00

  • Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene.

    abstract：:Psoriasis is an immune-mediated skin disorder that is inherited as a multifactorial trait. Linkage studies have clearly identified a primary disease susceptibility locus lying within the major histocompatibility complex (MHC), but have generated conflicting results for other genomic regions. To overcome this difficult...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddn091

    authors： Capon F,Bijlmakers MJ,Wolf N,Quaranta M,Huffmeier U,Allen M,Timms K,Abkevich V,Gutin A,Smith R,Warren RB,Young HS,Worthington J,Burden AD,Griffiths CE,Hayday A,Nestle FO,Reis A,Lanchbury J,Barker JN,Trembath RC

    更新日期：2008-07-01 00:00:00

  • Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity.

    abstract：:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mou...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.13.2009

    authors： Jana NR,Tanaka M,Wang Gh,Nukina N

    更新日期：2000-08-12 00:00:00

  • A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis.

    abstract：:Epidermolytic hyperkeratosis (EHK) is a blistering skin disease inherited as an autosomal-dominant trait. The disease is caused by genetic defects of the epidermal keratin K1 or K10, leading to an impaired tonofilament network of differentiating epidermal cells. Here, we describe for the first time a kindred with rece...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl028

    authors： Müller FB,Huber M,Kinaciyan T,Hausser I,Schaffrath C,Krieg T,Hohl D,Korge BP,Arin MJ

    更新日期：2006-04-01 00:00:00

  • Systematic analysis of the gerontome reveals links between aging and age-related diseases.

    abstract：:In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the ‘gerontome’. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pa...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw307

    authors： Fernandes M,Wan C,Tacutu R,Barardo D,Rajput A,Wang J,Thoppil H,Thornton D,Yang C,Freitas A,de Magalhães JP

    更新日期：2016-11-01 00:00:00

  • Long, abundantly expressed non-coding transcripts are altered in cancer.

    abstract：:Recent studies with tiling arrays have revealed more genomic transcription than previously anticipated. Whole new groups of non-coding transcripts (NCTs) have been detected. Some of these NCTs, including miRNAs, can regulate gene expression. To date, most known NCTs studied have been relatively short, but several impo...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm336

    authors： Perez DS,Hoage TR,Pritchett JR,Ducharme-Smith AL,Halling ML,Ganapathiraju SC,Streng PS,Smith DI

    更新日期：2008-03-01 00:00:00

  • The autoimmunity-associated BLK haplotype exhibits cis-regulatory effects on mRNA and protein expression that are prominently observed in B cells early in development.

    abstract：:The gene B lymphocyte kinase (BLK) is associated with rheumatoid arthritis, systemic lupus erythematosus and several other autoimmune disorders. The disease risk haplotype is known to be associated with reduced expression of BLK mRNA transcript in human B cell lines; however, little is known about cis-regulation of BL...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds220

    authors： Simpfendorfer KR,Olsson LM,Manjarrez Orduño N,Khalili H,Simeone AM,Katz MS,Lee AT,Diamond B,Gregersen PK

    更新日期：2012-09-01 00:00:00

  • Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteins.

    abstract：:X-Linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by reduced peroxisomal very long chain fatty acid (VLCFA) beta-oxidation. The X - ALD gene product (ALDP) is a peroxisomal transmembrane protein with an ATP binding cassette (ABC). ALDP and three other ABC proteins (PMP70, ALDR, P70R) ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.2.239

    authors： Braiterman LT,Zheng S,Watkins PA,Geraghty MT,Johnson G,McGuinness MC,Moser AB,Smith KD

    更新日期：1998-02-01 00:00:00

  • Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation.

    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

    authors： Krushkal J,Xiong M,Ferrell R,Sing CF,Turner ST,Boerwinkle E

    更新日期：1998-09-01 00:00:00

  • BLM helicase facilitates RNA polymerase I-mediated ribosomal RNA transcription.

    abstract：:Bloom's syndrome (BS) is an autosomal recessive disorder that is invariably characterized by severe growth retardation and cancer predisposition. The Bloom's syndrome helicase (BLM), mutations of which lead to BS, localizes to promyelocytic leukemia protein bodies and to the nucleolus of the cell, the site of RNA poly...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr545

    authors： Grierson PM,Lillard K,Behbehani GK,Combs KA,Bhattacharyya S,Acharya S,Groden J

    更新日期：2012-03-01 00:00:00

  • Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians.

    abstract：:The electrocardiogram has several advantages in detecting cardiac arrhythmia-it is readily available, noninvasive and cost-efficient. Recent genome-wide association studies have identified single-nucleotide polymorphisms that are associated with electrocardiogram measures. We performed a genome-wide association study ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu374

    authors： Hong KW,Lim JE,Kim JW,Tabara Y,Ueshima H,Miki T,Matsuda F,Cho YS,Kim Y,Oh B

    更新日期：2014-12-15 00:00:00