Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos.

Abstract:

:Imprinting is an epigenetic mechanism leading to mono-allelic expression of imprinted genes. In order to inherit the differential epigenetic imprints from one generation to the next, these imprints have to be erased in the primordial germ cells and re-established in a sex-specific manner during gametogenesis. The exact timing of the imprint resetting is not yet known and the use of immature gametes in assisted reproductive technologies may therefore lead to abnormal imprinting and related diseases. Imprinting is associated with differential allelic methylation in a CpG-context. We studied the methylation patterns of the imprint control (IC) region of the human SNRPN-gene in human spermatozoa, oocytes in different developmental stages [germinal vesicle (GV), metaphase I and metaphase II oocytes] and in preimplantation embryos using the bisulphite sequencing technique. In the spermatozoa, almost all potential methylation sites were unmethylated whereas mainly methylated patterns were found in the oocytes at different developmental stages. In the embryos, an average methylation pattern of 53% was found indicating that the imprints, which have been set during gametogenesis, are stably maintained in the preimplantation embryo. Our results indicate that the maternal imprints for the IC-region of the human SNRPN-gene are already re-established at the GV stage and that they are not re-established in a late oocyte stage or after fertilization as previously reported. Recent advances in assisted reproductive technologies raise questions concerning safety and the epigenetic risks involved. Our study was the first to check the methylation imprints in human pre-implantation embryos and oocytes at different developmental stages.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Geuns E,De Rycke M,Van Steirteghem A,Liebaers I

doi

10.1093/hmg/ddg315

subject

Has Abstract

pub_date

2003-11-15 00:00:00

pages

2873-9

issue

22

eissn

0964-6906

issn

1460-2083

pii

ddg315

journal_volume

12

pub_type

杂志文章
  • 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders.

    abstract::Human chromosome 15q11-13 is a complex locus containing imprinted genes as well as a cluster of three GABA(A) receptor subunit (GABR) genes-GABRB3, GABRA5 and GABRG3. Deletion or duplication of 15q11-13 GABR genes occurs in multiple human neurodevelopmental disorders including Prader-Willi syndrome (PWS), Angelman syn...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddm014

    authors: Hogart A,Nagarajan RP,Patzel KA,Yasui DH,Lasalle JM

    更新日期:2007-03-15 00:00:00

  • Mouse tissue culture models of unstable triplet repeats: in vitro selection for larger alleles, mutational expansion bias and tissue specificity, but no association with cell division rates.

    abstract::The expansion of CAG.CTG trinucleotide repeats has been associated with an increasing number of human diseases. Once into the expanded disease-associated range, the repeats become dramatically unstable in the germline and also throughout the soma. Instability is expansion-biased, contributing towards the unusual genet...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/10.8.845

    authors: Gomes-Pereira M,Fortune MT,Monckton DG

    更新日期:2001-04-01 00:00:00

  • Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease.

    abstract::Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in one of three genes: PKD1 on chromosome 16 accounts for approximately 85% of cases whereas PKD2 on chromosome 4 accounts for approximately 15%. Mutations in the PKD3 gene are rare. All patients present with similar clinical phenotypes, and t...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/8.3.509

    authors: Koptides M,Hadjimichael C,Koupepidou P,Pierides A,Constantinou Deltas C

    更新日期:1999-03-01 00:00:00

  • Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy.

    abstract::Lafora progressive myoclonus epilepsy, caused by defective laforin or malin, insidiously present in normal teenagers with cognitive decline, followed by rapidly intractable epilepsy, dementia and death. Pathology reveals neurodegeneration with neurofibrillary tangle formation and Lafora bodies (LBs). LBs are deposits ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddi306

    authors: Lohi H,Ianzano L,Zhao XC,Chan EM,Turnbull J,Scherer SW,Ackerley CA,Minassian BA

    更新日期:2005-09-15 00:00:00

  • Cellular stressors may alter islet hormone cell proportions by moderation of alternative splicing patterns.

    abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz094

    authors: Jeffery N,Richardson S,Chambers D,Morgan NG,Harries LW

    更新日期:2019-08-15 00:00:00

  • Allele-specific replication timing in imprinted domains: absence of asynchrony at several loci.

    abstract::Using a bromodeoxyuridine incorporation method to detect replicated DNA, we studied allele-specific replication of several sites within the human Prader-Willi/Angelman and IGF2/H19 imprinted regions. No obvious allele-specific differences in time of replication were detected at most loci previously reported to replica...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/4.12.2287

    authors: Kawame H,Gartler SM,Hansen RS

    更新日期:1995-12-01 00:00:00

  • C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity.

    abstract::P/Q-type voltage-gated calcium channels are regulated, in part, through the cytoplasmic C-terminus of their alpha1A subunit. Genetic absence or alteration of the C-terminus leads to abnormal channel function and neurological disease. Here, we show that the terminal 60-75 kDa of the endogenous alpha1A C-terminus is cle...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl080

    authors: Kordasiewicz HB,Thompson RM,Clark HB,Gomez CM

    更新日期:2006-05-15 00:00:00

  • Biologically active molecules that reduce polyglutamine aggregation and toxicity.

    abstract::Polyglutamine expansion in certain proteins causes neurodegeneration in inherited disorders such as Huntington disease and X-linked spinobulbar muscular atrophy. Polyglutamine tracts promote protein aggregation in vitro and in vivo with a strict length-dependence that strongly implicates alternative protein folding an...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl135

    authors: Desai UA,Pallos J,Ma AA,Stockwell BR,Thompson LM,Marsh JL,Diamond MI

    更新日期:2006-07-01 00:00:00

  • Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome.

    abstract::Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 e...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddt640

    authors: Yasui DH,Gonzales ML,Aflatooni JO,Crary FK,Hu DJ,Gavino BJ,Golub MS,Vincent JB,Carolyn Schanen N,Olson CO,Rastegar M,Lasalle JM

    更新日期:2014-05-01 00:00:00

  • Genotype-phenotype correlation in von Hippel-Lindau syndrome.

    abstract::The von Hippel-Lindau (VHL) syndrome (OMIM 193300) is an autosomal dominant disorder caused by deletions or mutations in a tumor suppressor gene on human chromosome 3p25. It is characterized clinically by vascular tumors including benign hemangioblastomas of the cerebellum, spine, brain stem and retina. Clear-cell ren...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审

    doi:10.1093/hmg/10.7.763

    authors: Friedrich CA

    更新日期:2001-04-01 00:00:00

  • Chemical genetics unveils a key role of mitochondrial dynamics, cytochrome c release and IP3R activity in muscular dystrophy.

    abstract::Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. The subcellular mechanisms of DMD remain poorly understood and there is currently no curative treatment available. Using a Caenorhabditis elegans model for DMD as a pharmacologic and genetic tool, we found that cyc...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddt302

    authors: Giacomotto J,Brouilly N,Walter L,Mariol MC,Berger J,Ségalat L,Becker TS,Currie PD,Gieseler K

    更新日期:2013-11-15 00:00:00

  • FGFR3 is a target of the homeobox transcription factor SHOX in limb development.

    abstract::The short stature homeobox gene SHOX encodes a transcription factor which is important for normal limb development. In humans, SHOX deficiency has been associated with various short stature syndromes including Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia and Turner syndrome as well as non-syndromic i...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr030

    authors: Decker E,Durand C,Bender S,Rödelsperger C,Glaser A,Hecht J,Schneider KU,Rappold G

    更新日期:2011-04-15 00:00:00

  • Protein phosphatase 1 regulates huntingtin exon 1 aggregation and toxicity.

    abstract::Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregati...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddx260

    authors: Branco-Santos J,Herrera F,Poças GM,Pires-Afonso Y,Giorgini F,Domingos PM,Outeiro TF

    更新日期:2017-10-01 00:00:00

  • RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity.

    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

    authors: Lipska BK,Mitkus S,Caruso M,Hyde TM,Chen J,Vakkalanka R,Straub RE,Weinberger DR,Kleinman JE

    更新日期:2006-09-15 00:00:00

  • Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.

    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

    authors: Zhang L,Cui X,Han Y,Park KS,Gao X,Zhang X,Yuan Z,Hu Y,Hsu CW,Li X,Bassuk AG,Mahajan VB,Wang NK,Tsang SH

    更新日期:2019-10-15 00:00:00

  • Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility.

    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

    authors: Foresta C,Ferlin A,Moro E

    更新日期:2000-05-01 00:00:00

  • Structural features of normal and mutant human lysosomal glycoside hydrolases deduced from bioinformatics analysis.

    abstract::Lysosomal storage diseases are due to inherited deficiencies in various enzymes involved in basic metabolic processes. As with other genetic diseases, accurate structure data for these enzymatic proteins should help in better understanding the molecular effects of mutations identified in patients with the correspondin...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审

    doi:10.1093/hmg/9.6.967

    authors: Durand P,Fabrega S,Henrissat B,Mornon JP,Lehn P

    更新日期:2000-04-12 00:00:00

  • Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer.

    abstract::Lung cancer demonstrates the highest mortality in the UK. Previous studies have implicated allelic loss at chromosome 17q in the development of non-small cell lung carcinoma (NSCLC), and a number of known and putative tumour-suppressor genes reside within this region. One candidate tumour-suppressor gene is cytoglobin...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl128

    authors: Xinarianos G,McRonald FE,Risk JM,Bowers NL,Nikolaidis G,Field JK,Liloglou T

    更新日期:2006-07-01 00:00:00

  • Missense mutations in β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) cause Walker-Warburg syndrome.

    abstract::Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result in defective αDG glycosylation and reduced ligand binding by α...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddt021

    authors: Buysse K,Riemersma M,Powell G,van Reeuwijk J,Chitayat D,Roscioli T,Kamsteeg EJ,van den Elzen C,van Beusekom E,Blaser S,Babul-Hirji R,Halliday W,Wright GJ,Stemple DL,Lin YY,Lefeber DJ,van Bokhoven H

    更新日期:2013-05-01 00:00:00

  • Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.

    abstract::Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage me...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,meta分析

    doi:10.1093/hmg/ddw181

    authors: Hou L,Bergen SE,Akula N,Song J,Hultman CM,Landén M,Adli M,Alda M,Ardau R,Arias B,Aubry JM,Backlund L,Badner JA,Barrett TB,Bauer M,Baune BT,Bellivier F,Benabarre A,Bengesser S,Berrettini WH,Bhattacharjee AK,Biern

    更新日期:2016-08-01 00:00:00

  • Expression of the PTEN tumour suppressor protein during human development.

    abstract::The tumour suppressor gene PTEN, localized to 10q23.3, is the susceptibility gene for Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba (BRR) syndrome, two hamartoma syndromes with an increased risk of breast and thyroid tumours. Somatic mutations have been found in a variety of human tumours. Functional studies have ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/9.11.1633

    authors: Gimm O,Attié-Bitach T,Lees JA,Vekemans M,Eng C

    更新日期:2000-07-01 00:00:00

  • Glutaredoxin deficiency exacerbates neurodegeneration in C. elegans models of Parkinson's disease.

    abstract::Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic neurons. Although the etiology of PD remains incompletely understood, oxidative stress has been implicated as an important contributor in the development of PD. Oxidative stress can lead to oxidation and functional perturbation of prot...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddu542

    authors: Johnson WM,Yao C,Siedlak SL,Wang W,Zhu X,Caldwell GA,Wilson-Delfosse AL,Mieyal JJ,Chen SG

    更新日期:2015-03-01 00:00:00

  • Over-expression of alpha-synuclein in human neural progenitors leads to specific changes in fate and differentiation.

    abstract::Missense mutations and extra copies of the alpha-Synuclein gene result in Parkinson disease (PD). Human stem and progenitor cells can be expanded from embryonic tissues and provide a source of non-transformed neural cells to explore the effects of these pathogenic mutations specifically in human nervous tissue. We ove...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddm008

    authors: Schneider BL,Seehus CR,Capowski EE,Aebischer P,Zhang SC,Svendsen CN

    更新日期:2007-03-15 00:00:00

  • The selective footprints of viral pressures at the human RIG-I-like receptor family.

    abstract::The RIG-I-like receptors (RLRs)--RIG-I, IFIH1 (or MDA5) and LGP2--are thought to be key actors in the innate immune system, as they play a major role in sensing RNA viruses in the cytosol of host cells. Despite the increasingly recognized importance of the RLR family in antiviral immunity, no population genetic studie...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr377

    authors: Vasseur E,Patin E,Laval G,Pajon S,Fornarino S,Crouau-Roy B,Quintana-Murci L

    更新日期:2011-11-15 00:00:00

  • Naturally occurring germline and tumor-associated mutations within the ATP-binding motifs of PTEN lead to oxidative damage of DNA associated with decreased nuclear p53.

    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

    authors: He X,Ni Y,Wang Y,Romigh T,Eng C

    更新日期:2011-01-01 00:00:00

  • Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy.

    abstract::X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) an...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr536

    authors: Schlüter A,Espinosa L,Fourcade S,Galino J,López E,Ilieva E,Morató L,Asheuer M,Cook T,McLaren A,Reid J,Kelly F,Bates S,Aubourg P,Galea E,Pujol A

    更新日期:2012-03-01 00:00:00

  • Variegated yet non-random rod and cone photoreceptor disease patterns in RPGR-ORF15-associated retinal degeneration.

    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

    authors: Charng J,Cideciyan AV,Jacobson SG,Sumaroka A,Schwartz SB,Swider M,Roman AJ,Sheplock R,Anand M,Peden MC,Khanna H,Heon E,Wright AF,Swaroop A

    更新日期:2016-12-15 00:00:00

  • Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia.

    abstract::Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotid...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddt460

    authors: Dols-Icardo O,García-Redondo A,Rojas-García R,Sánchez-Valle R,Noguera A,Gómez-Tortosa E,Pastor P,Hernández I,Esteban-Pérez J,Suárez-Calvet M,Antón-Aguirre S,Amer G,Ortega-Cubero S,Blesa R,Fortea J,Alcolea D,Capdevila A,

    更新日期:2014-02-01 00:00:00

  • Kidins220 accumulates with tau in human Alzheimer's disease and related models: modulation of its calpain-processing by GSK3β/PP1 imbalance.

    abstract::Failures in neurotrophic support and signalling play key roles in Alzheimer's disease (AD) pathogenesis. We previously demonstrated that downregulation of the neurotrophin effector Kinase D interacting substrate (Kidins220) by excitotoxicity and cerebral ischaemia contributed to neuronal death. This downregulation, tr...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/dds446

    authors: López-Menéndez C,Gamir-Morralla A,Jurado-Arjona J,Higuero AM,Campanero MR,Ferrer I,Hernández F,Ávila J,Díaz-Guerra M,Iglesias T

    更新日期:2013-02-01 00:00:00

  • Somatic sequence variation at the Friedreich ataxia locus includes complete contraction of the expanded GAA triplet repeat, significant length variation in serially passaged lymphoblasts and enhanced mutagenesis in the flanking sequence.

    abstract::The vast majority of Friedreich ataxia patients are homozygous for large GAA triplet repeat expansions in intron 1 of the X25 gene. Instability of the expanded GAA repeat was examined in 23 chromosomes bearing 97-1250 triplets in lymphoblastoid cell lines passaged 20-39 times. Southern analyses revealed 18 events of s...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/8.13.2425

    authors: Bidichandani SI,Purandare SM,Taylor EE,Gumin G,Machkhas H,Harati Y,Gibbs RA,Ashizawa T,Patel PI

    更新日期:1999-12-01 00:00:00