			Home About us Contact

Monoallelic Expression (monoallelic + expression)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma

MOLECULAR CARCINOGENESIS, Issue 4 2001
Masakazu Kohda
Abstract Genomic imprinting is a parental origin,specific chromosomal modification that causes differential expression of maternal and paternal alleles of a gene. Accumulating evidence suggests that deregulation of imprinted genes, including loss of imprinting (LOI), plays a role in oncogenesis. In the present study, we investigated allelic expression of six imprinted genes in human lung adenocarcinomas as well as in matched normal lung tissue. Informative cases showing heterozygosity for the gene of interest were selected from 35 patients. LOI of the insulin-like growth factor 2 gene (IGF2) and mesoderm-specific transcript (MEST, also known as paternally expressed gene 1) was noted in 47% (seven of 15) and 85% (11 of 13) of informative cases, respectively. Monoallelic expression was maintained in all the matched normal tissues examined. LOI of IGF2 was seen more frequently in moderately to poorly differentiated adenocarcinomas. In contrast, H19, small nuclear ribonucleoprotein,associated polypeptide N gene (SNRPN), necdin gene (NDN), and long QT intronic transcript 1 (LIT1) exhibited consistent monoallelic expression in all the informative samples. These findings indicated that independent deregulation took place in imprinted genes and suggested that aberrant imprinting of IGF2 and MEST was involved in the development of lung adenocarcinoma. © 2001 Wiley-Liss, Inc. [source]

Analysis of allelic expression patterns of IL-2, IL-3, IL-4, and IL-13 in human CD4+ T,cell clones

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2003
Jean-Pierre Bayley
Abstract The occurrence of monoallelic expression of cytokine genes in single cells has been convincingly demonstrated, but there have been few reports of this phenomenon in T,cell clones. Here we describe studies on the expression of alleles of the human genes encoding IL-2, IL-3, IL-4, and IL-13 in human CD4+ T,cell clones. In contrast to the results reported in mouse T,cell clones andsingle human T,cells, we found no evidence for the monoallelic expression of the IL-2, IL-3, and IL-13 genes. The gene for IL-4 showed an imbalance in expression from each allele, indicating differential expression of IL-4 alleles within or between IL-4-expressing cells. [source]

SELF-IMPOSED SILENCE: PARENTAL ANTAGONISM AND THE EVOLUTION OF X-CHROMOSOME INACTIVATION

EVOLUTION, Issue 3 2006
David Haig
Abstract A model is proposed for the evolution of X-chromosome inactivation (XCI) in which natural selection initially favors the silencing of paternally derived alleles of X-linked demand inhibitors. The compensatory upregulation of maternally derived alleles establishes a requirement for monoallelic expression in females. For this reason, XCI is self-reinforcing once established. However, inactivation of a particular X chromosome is not. Random XCI (rXCI) is favored over paternal XCI because rXCI reduces the costs of functional hemizygosity in females. Once present, rXCI favors the evolution of locus-by-locus imprinting of X-linked loci, which creates an evolutionary dynamic in which different chromosomes compete to remain active. [source]

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease,

HUMAN MUTATION, Issue 6 2010
Gerassimos E. Voutsinas
Abstract Genetic alterations in the alpha-synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady-state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild-type-allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis. Hum Mutat 31:1,7, 2010. © 2010 Wiley-Liss, Inc. [source]

Physiological functions of imprinted genes

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2002
Benjamin Tycko
Genomic imprinting in gametogenesis marks a subset of mammalian genes for parent-of-origin-dependent monoallelic expression in the offspring. Embryological and classical genetic experiments in mice that uncovered the existence of genomic imprinting nearly two decades ago produced abnormalities of growth or behavior, without severe developmental malformations. Since then, the identification and manipulation of individual imprinted genes has continued to suggest that the diverse products of these genes are largely devoted to controlling pre- and post-natal growth, as well as brain function and behavior. Here, we review this evidence, and link our discussion to a website (http://www.otago.ac.nz/IGC) containing a comprehensive database of imprinted genes. Ultimately, these data will answer the long-debated question of whether there is a coherent biological rationale for imprinting. © 2002 Wiley-Liss, Inc. [source]

Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma

Imprinting on chromosome 20: Tissue-specific imprinting and imprinting mutations in the GNAS locus,

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010
Gavin Kelsey
Abstract The GNAS locus on chromosome 20q13.11 is the archetypal complex imprinted locus. It comprises a bewildering array of alternative transcripts determined by differentially imprinted promoters which encode distinct proteins. It also provides the classic example of tissue-specific imprinted gene expression, in which the canonical GNAS transcript coding for Gs, is expressed predominantly from the maternal allele in a set of seemingly unrelated tissues. Functionally, this rather obscure imprinting is nevertheless of considerable clinical significance, as it dictates the nature of the disease caused by inactivating mutations in Gs,, with end organ hormone resistance specifically on maternal transmission (pseudohypoparathyroidism type 1a, PHP1a). In addition, there is a bona fide imprinting disorder, PHP1b, which is caused specifically by DNA methylation defects in the differentially methylated regions (DMRs) that determine tissue-specific monoallelic expression of GNAS. Although the genetic defect in PHP1a and the disrupted imprinting in PHP1b both essentially result in profound reduction of Gs, activity in tissues with monoallelic GNAS expression, and despite a growing awareness of the overlap in these two conditions, there are important pathophysiological differences between the two whose basis is not fully understood. PHP1b is one of the only imprinted gene syndromes in which cis -acting mutations have been discovered that disrupt methylation of germline-derived imprint marks; such imprinting mutations in GNAS are helping to provide important new insights into the mechanisms of imprinting establishment generally. © 2010 Wiley-Liss, Inc. [source]

Evidence for cis -acting regulation of ANK3 and CACNA1C gene expression

BIPOLAR DISORDERS, Issue 4 2010
Emma M Quinn
Quinn EM, Hill M, Anney R, Gill M, Corvin AP, Morris DW. Evidence for cis -acting regulation of ANK3 and CACNA1C gene expression. Bipolar Disord 2010: 12: 440,445. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives:, Genome-wide association studies (GWAS) have identified Ankyrin-G (ANK3) and the ,-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) as susceptibility genes for bipolar disorder. Available biological information on these genes suggests a potential molecular mechanism involving ion channel dysfunction. The associated single nucleotide polymorphisms (SNPs) at ANK3 (rs10994336) and CACNA1C (rs1006737) are both intronic with no obvious impact on gene function. We investigated whether, instead of affecting protein function, these risk variants might impact on gene regulation affecting expression. Methods:, We have done this by testing for allelic expression imbalance (AEI) to identify cis -acting regulatory polymorphisms. Results:, We identified evidence of cis -acting variation at both loci in HapMap Caucasian Europeans from Utah (CEU) lymphoblastoid cell lines. There was considerable evidence of AEI at ANK3 with more than half of all heterozygous samples (21 out of 34) for marker SNP rs3750800 showing AEI and a small number of samples showing near monoallelic expression. The AEI at either gene could not be attributed to the GWAS-associated SNPs. Conclusions:, These data indicate that there is genetic variation local to both genes affecting their expression, but that this variation is not responsible for increasing risk of bipolar disorder. [source]