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Allelic Expression (allelic + expression)

Distribution by Scientific Domains
Medical Sciences60%
Life Sciences40%

Selected Abstracts

Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype,phenotype correlations,

HUMAN MUTATION, Issue 7 2009
Jordan P. Lerner-Ellis
Abstract Methylmalonic aciduria and homocystinuria, cblC type, is a rare disorder of intracellular vitamin B12 (cobalamin [Cbl]) metabolism caused by mutations in the MMACHC gene. MMACHC was sequenced from the gDNA of 118 cblC individuals. Eleven novel mutations were identified, as well as 23 mutations that were observed previously. Six sequence variants capture haplotype diversity in individuals across the MMACHC interval. Genotype,phenotype correlations of common mutations were apparent; individuals with c.394C>T tend to present with late-onset disease whereas patients with c.331C>T and c.271dupA tend to present in infancy. Other missense variants were also associated with late- or early-onset disease. Allelic expression analysis was carried out on human cblC fibroblasts compound heterozygous for different combinations of mutations including c.271dupA, c.331C>T, c.394C>T, and c.482G>A. The early-onset c.271dupA mutation was consistently underexpressed when compared to control alleles and the late-onset c.394C>T and c.482G>A mutations. The early-onset c.331C>T mutation was also underexpressed when compared to control alleles and the c.394C>T mutation. Levels of MMACHC mRNA transcript in cell lines homozygous for c.271dupA, c.331C>T, and c.394C>T were assessed using quantitative real-time RT-PCR. Cell lines homozygous for the late onset c.394C>T mutation had significantly higher levels of transcript when compared to cell lines homozygous for the early-onset mutations. Differential or preferential MMACHC transcript levels may provide a clue as to why individuals carrying c.394C>T generally present later in life. Hum Mutat 30:1,10, 2009. © 2009 Wiley-Liss, Inc. [source]

Sodium channel gene expression in mosquitoes, Aedes albopictus (S.)

INSECT SCIENCE, Issue 6 2006
NANNAN LIU
Abstract A mosquito strain of Aedes albopictus, HAmAalG0, from Huntsville, Alabama, USA, showed a normal susceptibility and low tolerance to permethrin and resmethrin (pyrethroid insecticides) compared to a susceptible Ikaken strain, even though these pyrethroid insecticides have been used in the field for a long period of time in Alabama. Recently, we treated HAmAalG0 in the laboratory with permethrin for five generations and detected no significant change in the level of resistance to permethrin in the selected mosquitoes, HAmAalG5, compared with the parental strain HAmAalG0. We then examined the allelic expression at the L-to-F kdr site of the sodium channel gene in the Aedes mosquitoes to address our hypothesis that the L-to-F kdr mutation was not present in HAmAalG0 and HAmAalG5 mosquitoes. We found that every tested individual in Ikaken, HAmAalG0, and HAmAalG5 populations expressed a codon of CTA at the L-to-F kdr site encoding Leu, strongly corresponding to their susceptibility to insecticides. [source]

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]

Functional analysis of the osteoarthritis susceptibility,associated GDF5 regulatory polymorphism

ARTHRITIS & RHEUMATISM, Issue 7 2009
Rainer J. Egli
Objective Single-nucleotide polymorphism (SNP) rs143383 (T to C) in the 5,-untranslated region (5,-UTR) of GDF5 has recently been reported to be associated with osteoarthritis (OA) susceptibility, with lower expression of the risk-associated T allele observed in vitro and in vivo. The in vivo studies were performed on cartilage tissue from OA patients. The present study was undertaken to expand the analysis of the effect of this SNP on GDF5 allelic expression to more joint tissue types, to investigate for cis and trans factors that interact with the SNP, and to examine novel cis -acting GDF5 regulatory polymorphisms. Methods Tissue samples were collected from OA patients undergoing joint replacement of the hip or knee. Nucleic acid was extracted, and, using rs143383 and an assay that discriminates and quantifies allelic expression, the relative amount of GDF5 expression from the T and C alleles was measured. Additional common variants in the GDF5 transcript sequence were interrogated as potential regulatory elements using allelic expression and luciferase reporter assays, and electrophoretic mobility shift assays were used to search for trans factors binding to rs143383. Results We observed a consistent allelic expression imbalance of GDF5 in all tissues tested, implying that the functional effect mediated by rs143383 on GDF5 expression is joint-wide. We identified a second polymorphism, located in the 3,-UTR of GDF5, that influenced allelic expression of the gene independent of rs143383. Finally, we observed differential binding of deformed epidermal autoregulatory factor 1 (DEAF-1) to the 2 alleles of rs143383. Conclusion These findings show that the OA susceptibility mediated by polymorphism in GDF5 is not restricted to cartilage, emphasizing the need to consider the disease as involving the whole joint. The existence of an additional cis -acting regulatory polymorphism highlights the complexity of the regulation of expression of this important OA susceptibility locus. DEAF-1 is a trans -acting factor that merits further investigation as a potential tool for modulating GDF5 expression. [source]