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 Genetjournal_title
Human molecular geneticsauthors
Geuns E,De Rycke M,Van Steirteghem A,Liebaers Idoi
10.1093/hmg/ddg315subject
Has Abstractpub_date
2003-11-15 00:00:00pages
2873-9issue
22eissn
0964-6906issn
1460-2083pii
ddg315journal_volume
12pub_type
杂志文章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
更新日期:2007-03-15 00:00:00
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
更新日期:2001-04-01 00:00:00
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
更新日期:1999-03-01 00:00:00
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
更新日期:2005-09-15 00:00:00
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
更新日期:2019-08-15 00:00:00
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
更新日期:1995-12-01 00:00:00
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
更新日期:2006-05-15 00:00:00
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
更新日期:2006-07-01 00:00:00
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
更新日期:2014-05-01 00:00:00
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
更新日期:2001-04-01 00:00:00
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
更新日期:2013-11-15 00:00:00
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
更新日期:2011-04-15 00:00:00
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
更新日期:2017-10-01 00:00:00
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
更新日期:2006-09-15 00:00:00
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
更新日期:2019-10-15 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::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
更新日期:2000-04-12 00:00:00
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
更新日期:2006-07-01 00:00:00
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
更新日期:2013-05-01 00:00:00
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
更新日期:2016-08-01 00:00:00
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
更新日期:2000-07-01 00:00:00
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
更新日期:2015-03-01 00:00:00
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
更新日期:2007-03-15 00:00:00
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
更新日期:2011-11-15 00:00:00
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
更新日期:2011-01-01 00:00:00
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
更新日期:2012-03-01 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::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
更新日期:2014-02-01 00:00:00
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
更新日期:2013-02-01 00:00:00
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
更新日期:1999-12-01 00:00:00