Protein Coding Region (protein + coding_region)

Distribution by Scientific Domains


Selected Abstracts


Human alcoholism studies of genes identified through mouse quantitative trait locus analysis

ADDICTION BIOLOGY, Issue 4 2002
Marissa A. Ehringer
Coding region DNA sequence variants have been recently identified in several QTL candidate genes in a mouse model of differential sensitivity to alcohol [inbred long-sleep (ILS) and inbred short-sleep (ISS)]. This work has been extended into a human population characterized for their initial level of response to alcohol (LR). The coding region of one of the most promising of these candidate genes, zinc finger 133 (Znf133), has been sequenced completely in 50 individuals who participated in alcohol challenges at approximately age 20 and have been followed subsequently for the last 15 years. PCR products were obtained for the protein coding region of ZNF133 using human genomic DNA and directly sequenced using automated sequencers. Novel single nucleotide polymorphisms (SNPs) were detected by analyzing the sequence data using a suite of bioinformatics programs including Consed, Phred, Phrap and Polyphred. Five human SNPs were detected, two that correspond to amino acid changes in the protein, two that are silent DNA changes and one located in an intron. In this small sample, no significant association between any of the SNPs and alcohol diagnosis was detected. A follow-up of these SNPs in a larger sample should allow a more definitive conclusion to be reached. Significantly, the data presented here demonstrate the feasibility of directly testing genes in human alcoholic populations that had been identified first by comparative DNA sequencing of candidate genes located within mouse alcohol-related QTLs, even without detailed knowledge of the gene's function. [source]


Functional analysis of polyomavirus BK non-coding control region quasispecies from kidney transplant recipients

JOURNAL OF MEDICAL VIROLOGY, Issue 11 2009
Gunn-Hege Olsen
Abstract Replication of the human polyomavirus BK (BKV) in renal tubular epithelial cells causes viruria and BKV-nephropathy in kidney transplant recipients. Following prolonged high-level BKV replication, rearrangement of the archetype non-coding control region (NCCR) leads to a mixture of BKV variants. The aim of this study was to compare potential functional differences of 12 rearranged (rr)-NCCR variants with the archetype (ww)-NCCR (WWT) found in allograft biopsies or urine from three kidney transplant recipients including two with BKV-nephropathy. Twelve different rr-NCCRs and one archetype ww-NCCR were inserted between the early and late protein coding region of BKV(Dunlop) to make recombinant BKV genomes for transfection into Vero cells. Immunoblotting, immunofluorescence staining, and quantitative PCR demonstrated that viral protein expression and extracellular BKV loads of 10 rr-NCCR variants were similar or higher than observed for the ww-NCCR BKV. Two rr-NCCR variants (RH-2 and RH-19) were non-functional. The functional rr-NCCRs produced infectious progeny successfully infecting primary renal proximal tubular epithelial cells. The number of infected cells and extracellular BKV loads corresponded to the activity seen in Vero cells. Three rr-NCCR variants (RH-1, RH-10, RH-13) only gave rise to a few infected cells similar to ww-NCCR, whereas seven variants had intermediate activity (RH-5, RH-6, RH-8, RH-9, RH-11) or high replication activity (RH-7 and RH-18) with several hundred infected cells per well. The results indicate that both functional and non-functional BKV rr-NCCR variants arise during BKV replication in kidney transplant recipients and that most functional rr-NCCR variants confer a higher replication capacity than archetype ww-NCCR. J. Med. Virol. 81:1959,1967, 2009. © 2009 Wiley-Liss, Inc. [source]


Genetic and phenotypic diversity of echovirus 30 strains and pathogenesis of type 1 diabetes

JOURNAL OF MEDICAL VIROLOGY, Issue 7 2007
A. Paananen
Abstract Several enterovirus serotypes should be considered as potentially diabetogenic. The capacity of an enterovirus to kill or impair the functions of human ,-cells can vary among the strains within a given serotype as shown previously for echovirus 9 and 30 (E-30). The evolution of E-30 has also shown patterns correlating with the global increase of type 1 diabetes incidence. In the present study, antigenic properties of a set of E-30 isolates were investigated and the results correlated with the previously documented ,-cell destructive phenotype of the strains, or to genetic clustering of the strains. No simple correlation between the three properties was observed. A full-length infectious clone was constructed and sequenced from one of the isolates found to be most destructive to ,-cells (E-30/14916net87). Phylogenetic analyses demonstrated that this strain was closely related to the E-30 prototype strain at the capsid coding region while outside the capsid region prototype strains of several other human enterovirus B serotypes clustered more closely. This suggests that the relatively greater pathogenicity of the strain might be based on properties of the genome outside of the structural protein coding region. Neutralizing antibody assays on sera from 100 type 1 diabetic patients and 100 controls using three different E-30 strains did not reveal differences between the groups. This finding does not support a previous proposition of aberrant antibody responses to E-30 in diabetic patients. It is concluded that identification of the genetic counterparts of pathogenicity of E-30 strains requires further studies. J. Med. Virol. 79:945-955, 2007. © 2007 Wiley-Liss, Inc. [source]


Molecular Analysis of Zucchini yellow mosaic virus Isolates from Hangzhou, China

JOURNAL OF PHYTOPATHOLOGY, Issue 6 2003
M.-F. Zhao
Abstract Isolates of Zucchini yellow mosaic virus were obtained from different cucurbit crops in Hangzhou city, China. The complete nucleotide sequences of four isolates and the 3,-terminal sequences, including the coat protein coding region, of four others were determined and then compared with other available sequences. Phylogenetic analysis of the coat protein nucleotide sequences showed that these isolates fell into three significant groups, one of which (designated group III) consisted exclusively of Chinese isolates and is reported for the first time. Comparisons over the completely sequenced genomes showed that, typically for potyviruses, the 5,-end of the genome was usually the most variable but that the group III isolate differed from the others most significantly in the N-terminal part of the coat protein. Partially sequenced group III isolates also varied from other isolates in this region. Group III isolates appear to differ biologically from the other isolates because they do not cause symptoms in watermelon fruit but induce more severe symptoms on the watermelon leaves. [source]