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At least 757 records · Page 42Linked to original sources
PubMed1991

Evolution of the rat kallikrein gene family: gene conversion leads to functional diversity.

Kallikrein-like simple serine proteases are encoded by closely related members of a gene family in several mammalian species. Molecular cloning and genomic Southern blot analysis after conventional and pulsed-field gel electrophoresis indicate that the rat kallikrein gene family comprises 15-20 members, probably closely linked at a single locus. Determination of the nucleotide sequences of the rGK-3, -4, and -6 genes here completes sequence data for a total of nine rat kallikrein family members. Comparison of the rat gene sequences to each other and to those of human and mouse kallikrein family genes reveals patterns of relatedness indicative of concerted evolution. Analysis of nucleotide sequence variants in kallikrein family members shows that most sequence variants are shared by multiple family members; the patterns of shared variants are complex and indicate multiple short gene conversions between family members. Sequence exchanges between family members generate novel assortments of variants in amino acid coding regions that may affect substrate specificity and thereby contribute to the diversity of enzyme activity. Furthermore, small sequence exchanges also may play a role in generating the diverse patterns of tissue-specific expression of rat family members. These analyses indicate an important role for gene conversion in the evolution of the functional diversity of these duplicated genes.

Amino Acid Sequence↗
PubMed2005

Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes.

AIMS/HYPOTHESIS: The proinflammatory cytokine TNF-alpha has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-alpha (TNF) has shown inconsistent associations with susceptibility to both conditions. Additionally, the coding non-synonymous variant T60N in the neighbouring LTA gene has been reported to be associated with type 2 diabetes. The present study aimed to obtain a robust assessment of the role of variation in the tightly linked TNF/LTA region in diabetes susceptibility by genotyping TNF and LTA variants in large case-control resources. MATERIALS AND METHODS: The G-308A and G-238A TNF promoter variants and the LTA T60N polymorphism were genotyped in two UK case samples that were ascertained for positive family history and/or early onset of type 2 diabetes (combined n=858) and in 1,257 ethnically matched controls. RESULTS: There were no significant associations between the T60N, G-308A or G-238A genotype and type 2 diabetes in the combined analysis (exact Cochran-Mantel-Haenszel statistic for ordered genotypes for T60N, p=0.69; for G-308A, p=0.51; for G-238A, p=0.16). CONCLUSIONS/INTERPRETATION: The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes. More comprehensive studies of the TNF/LTA locus in substantially larger sample sets are required to establish whether genome sequence variation at this locus truly influences susceptibility to type 2 diabetes.

Adult↗
PubMed1997

Effect of citrate on growth of Lactococcus lactis subsp. lactis in milk.

The effect of citrate on the growth of Lactococcus lactis subsp. lactis var. diacetylactis in milk has been investigated. Five strains of Lactococcus lactis subsp. lactis var. diacetylactis were compared to their citrate-negative variants, which lack the plasmid coding for citrate permease. In most cases, acidification kinetics and the final bacterial concentration of pure cultures of parental and variant strains did not differ significantly. Co-cultures of parental and variant strains, however, systematically tended towards the predominance of parental strains. Citrate metabolism is responsible for this change, since the predominance of citrate-positive strains was not observed in the absence of citrate. Continuous culture in milk enabled the difference in growth rates between the parental strain Lactococcus lactis subsp. lactis var. diacetylactis CDI1 and its citrate-negative variant to be quantified by following changes in the populations of the two co-cultured strains. At 26 degrees C, the growth rate of the parental strain was 7% higher than that of its citrate-negative variant. These results show that citrate metabolism slightly stimulates the growth of lactococci in milk.

Animals↗
PubMed2003

PrP Sc-like prion protein conformer in sudden infant death syndrome brain.

Nothing is known about the pathophysiology of sudden infant death syndrome (SIDS). Here we show the presence of misfolded prion protein (PrP(Sc)-like) in extracts of various sections of the brains of two SIDS victims. DNA sequence information for one of these (death at 12 days) revealed two nucleotide variants in the protein coding region of the PrP gene. This may be a key finding in the understanding of SIDS pathology, and may suggest ways for identifying risk factors for SIDS in newborn infants.

Adult↗
PubMed2002

Genomic structure and eight novel exonic polymorphisms of the human N-cadherin gene.

Analysis of the detailed genomic structure of human N-cadherin revealed that the 16-exon gene is more than 72 kb in length and that it consists of a mosaic of exons. Five repeated cadherin domains, a transmembrane domain, and a cytoplasmic domain are encoded by exons 4 to 13, 13 and 14, and 14 to 16, respectively. A search for molecular variants in the entire coding region in 96 Japanese individuals resulted in the identification of eight sequence polymorphisms including three CCT- or GCC-type trinucleotide repeat polymorphisms adjacent to the initiation codon and five other novel single-nucleoticle polymorphisms (SNPs) in the coding region. Three of the five SNPs accompanied an amino acid substitution: Ala118Thr, Ala826Thr, and Asn845Ser. Knowlege of the fine gene structure and eight novel polymorphisms will be useful for the genetic study of the role of N-cadherin in diseases involving cell adhesion in the brain and in cardiomyocytes.

Brain Neoplasms↗
PubMed2005

Identification of the cytolinker protein plectin in neuronal cells - expression of a rodless isoform in neurons of the rat superior cervical ganglion.

Plectin, a large (> 500 kDa) dumbbell-shaped cytolinker protein plays an important role in the organization of the cytoskeletal network and the maintenance of cell integrity in a wide variety of tissues and cell types. Earlier experiments revealed the presence of plectin in the central nervous system, whereas the expression in the peripheral nervous system remained unclear. Our results obtained with reverse transcriptase-PCR (RT-PCR) provide evidence that plectin is expressed in structures of the rat peripheral nervous system. In addition to well-characterized plectin transcripts we were able to reveal novel splicing variants affecting the region coding for the central rod domain. Previous studies report a high, but tissue-specific variability of the N-terminal domain of plectin due to alternatively spliced first coding exons and the optionally spliced small exons 2 alpha and 3 alpha. We demonstrate for the first time, using single-cell RT-PCR and immunocytochemistry, that plectin is expressed in neurons of the rat superior cervical ganglion (SCG). Plectin transcripts of single SCG neurons, starting with exon 1c as the first coding exon, contain the optionally spliced exon 2 alpha but lack exon 31. These data therefore suggest that plectin is expressed in rat SCG neurons as a rodless isoform with the molecular mass of 390 kDa.

Alternative Splicing↗
PubMed1996

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant.

The presenilin 1 (PS1) gene located on chromosome 14 has been linked with the majority of early-onset FAD. The normal biological role of PS1 as well as the mechanism by which mutations in PS1 cause FAD remains unknown. PS1 expression in platelets and the Dami megakaryocytic cell line was examined by Western blot analysis and RT-PCR. Using an anti-N-terminus PS1 antibody we detected PS1 immunoreactive bands of 44, 32 and 27 kDa in both cell types. After RT-PCR we observed that platelets and megakaryocytes carry at least four different PS1 transcripts. One of them is a novel PS1 splice variant that lacks the coding sequence for exon 10 resulting in a shorter 409 amino acid protein.

Alternative Splicing↗
PubMed1983

Modifications of a Trypanosoma b. brucei antigen gene repertoire by different DNA recombinational mechanisms.

In the Trypanosoma b. brucei AnTat 1.1C clone, the gene coding for the variant-specific surface antigen is telomeric and appears as a hybrid sequence, partially modified by gene conversion. This conversion is very similar to that observed in another AnTat 1.1-expressor clone (AnTat 1.1B). This sequence is not activated by duplicative transposition, although it could be activated by duplication in another clone (AnTat 1.10). Instead activation of the AnTat 1.1C gene seems operated by reciprocal recombination between its own telomere and the telomere carrying the previous (AnTat 1.16) ELC. Indeed, from the switch to AnTat 1.1C onward, the AnTat 1.16 ELC becomes a new silent member of its gene family, whereas in the variant directly derived from AnTat 1.1C (AnTat 1.3B), the AnTat 1.1C-containing telomere is lost, probably replaced by a large duplicate, at least 40 kb long, of the AnTat 1.3 gene-containing telomere. Different DNA rearrangement mechanisms used by the trypanosome to change its antigenic type thus contribute, by gain and loss of genes, to the evolution of the repertoire for surface antigens.

Animals↗
PubMed1988

Novel strand exchanges in V(D)J recombination.

We describe novel products of V(D)J recombination in which signal sequences become joined to coding elements, in contrast to the standard reaction whose products are junctions of two signal sequences or two coding elements. In this variant reaction, the recombination machinery evidently recognizes signal sequences and introduces strand breaks at the normal positions, but then connects the elements in unusual combinations. The lack of fixed directionality indicates that recombination sites are not uniquely aligned when strand exchange occurs. The discovery of these variant junctions suggests a model for the evolution of the antigen receptor loci.

Animals↗
PubMed1993

Amyloid precursor protein mRNA levels in the mononuclear blood cells of Alzheimer's and Down's patients.

Amyloid precursor protein (APP) is expressed by many non-neural tissues and it is possible that over-expression of the APP gene in non-neural tissue is responsible for the deposition of amyloid beta-protein in the brain and elsewhere. One possible source of beta-protein is circulating mononuclear blood cells which have previously been shown to express APP. To test this hypothesis, RNA was isolated from the mononuclear blood cells of patients suffering from Alzheimer's disease (n = 27), Down's syndrome (n = 13), senile dementia non-Alzheimer type (n = 14) and from normal individuals (n = 48). The relative abundance of mRNA coding for different splicing variants of the amyloid precursor protein (APP) mRNA was measured using multiprobe oligonucleotide solution hybridisation (MOSH). There was no significant difference in APP mRNA levels between any of the groups. This indicates that Alzheimer's disease is not characterised by an increase in production of APP in circulating mononuclear blood cells.

Adult↗
PubMed2006

Comparative genomics as a tool for gene discovery.

With the increasing availability of data from multiple eukaryotic genome sequencing projects, attention has focused on interspecific comparisons to discover novel genes and transcribed genomic sequences. Generally, these extrinsic strategies combine ab initio gene prediction with expression and/or homology data to identify conserved gene candidates between two or more genomes. Interspecific sequence analyses have proven invaluable for the improvement of existing annotations, automation of annotation, and identification of novel coding regions and splice variants. Further, comparative genomic approaches hold the promise of improved prediction of terminal or small exons, microRNA precursors, and small peptide-encoding open reading frames--sequence elements that are difficult to identify through purely intrinsic methodologies in the absence of experimental data.

Computational Biology↗
PubMed2006

Molecular cloning characterization and expression of porcine immunoreceptor SIRPalpha.

SWC3 is a porcine CD that has been the reference marker of myeloid lineage. It is expressed in every myelomonocytic cell from early bone marrow precursors. We have identified the molecule recognized by anti-SWC3 antibodies as a member of the signal-regulatory proteins (SIRPs)alpha family. Here, we describe the cloning of a cDNA coding for a porcine SIRPalpha protein. The sequence is 2470 nucleotides long and contains an open reading frame encoding a 507 amino acid sequence. The predicted polypeptide was composed of a 30 amino acids putative signal peptide, a 342 amino acid extracellular region, a 23 amino acid transmembrane segment and a 112 amino acid cytoplasmic domain. Analysis of the sequence reveals a high degree of homology with known SIRPs in other species, being easily identified the three extracellular Ig type domains and two cytoplasmic ITIM motifs characteristic of this molecule. The gene coding for porcine SIRPalpha has been mapped to porcine chromosome 17, in a region syntenic to the human chromosome 20 where SIRP genes have been mapped. During the analysis of SIRP gene expression in tissues by RT-PCR, we noticed the existence of a shorter mRNA, and cloned the corresponding cDNA. This coded for a splicing variant of SIRPalpha that lacked the two membrane proximal Ig domains. In transfection experiments, we have been able to show that anti-SWC3 antibodies recognize both forms of the molecule, mapping the SWC3 epitopes to the N-terminal IgV type domain.

Animals↗
PubMed2004

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression.

A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signalling pathways in a manner similar to that of oncoproteins of small DNA tumor viruses such as human papilloma virus or adenoviruses. However, in contrast to these DNA tumor viruses, HCMV infection fails to transform susceptible normal human cells. There is now growing evidence that tumor cells with disrupted regulatory and signalling pathways enable HCMV to modulate their properties including stimulation of cell proliferation, survival, invasion, production of angiogenic factors, and immunogenic properties. In contrast to previously suggested "hit and run" transformation we suggest that persistence in tumor cells is essential for HCMV to fully express its oncomodulatory effects. These effects are observed particularly in persistent HCMV infection and are mediated mainly by activity of HCMV regulatory proteins. In persistently HCMV-infected tumor cell lines - a selection of novel, slowly growing virus variants with changes in coding sequences for virus regulatory proteins takes place. As a result, oncomodulatory effects of HCMV infection may lead to a shift to more malignant phenotype of tumor cells contributing to tumor progression.

Cell Cycle↗
PubMed2006

FOXE1 gene mutation screening by multiplex PCR/DHPLC in CHARGE syndrome and syndromic and non-syndromic cleft palate.

Denaturing high-performance liquid chromatography (DHPLC) has established itself as one of the most powerful tools for DNA variation screening. FOXE1, a highly GC-rich gene involved in syndromic cleft palate, is under investigation in thyroid dysgenesis, nonsyndromic cleft palate and squamous cell carcinoma. A technique for fast and simultaneous detection of sequence variants in the entire coding region of the FOXEl gene based on multiplex PCR/DHPLC is presented here. Given its characteristics of high sensitivity and rapidity, the testing strategy developed by us appears to be a reliable approach for FOXE1 analysis in the screening of a large population at risk.

Base Sequence↗
PubMed2026

Uncovering hidden complexity in the Apis mellifera mitotranscriptome: a polyadenylation-centered perspective.

Mitochondrial transcription is gaining increasing attention as researchers seek to better understand the full coding potential of mitochondrial DNA (mtDNA). Emerging evidence suggests that mtDNA may encode additional elements beyond classical oxidative phosphorylation genes, pointing to a more complex transcriptional architecture than previously recognized. In this study, we explored the mitochondrial transcriptome of Apis mellifera (Insecta: Hymenoptera), with a particular focus on polyadenylation-associated features. Our analysis revealed that both sense and antisense transcripts undergo polyadenylation, although transcript abundance and poly(A) tail lengths varied markedly across mitochondrial genes. Several transcripts exhibited alternative isoforms, either extended or truncated, frequently including intergenic regions. These regions may represent functional non-coding elements or structural variants rather than conventional untranslated regions (UTRs). Interestingly, some transcripts also contained non-templated nucleotide additions particularly cytosine residues immediately upstream of the poly(A) tails. Monocistronic units that included portions of downstream intergenic regions were among the most abundantly represented, suggesting a possible regulatory role for these sequences. To experimentally validate our in silico findings, we performed RT-qPCR to assess relative gene expression and applied 3' RACE-PCR to define transcript boundaries. These approaches confirmed the presence of multiple transcript isoforms and supported the involvement of polyadenylation in shaping mitochondrial RNA diversity. Together, our findings reveal a previously underappreciated level of complexity in the A. mellifera mitochondrial transcriptome and highlight the potential regulatory significance of polyadenylation dynamics and intergenic region transcription.

Animals↗
PubMed2004

[Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients].

PURPOSE: Allelic variants of the gene coding for cytochrome P450 isoform 2C9 (CYP2C9), 2C9*2 and 2C9*3, were shown to increase sensitivity to warfarin in adults. In the elderly, the maintenance dose is influenced by acquired factors including comorbidities and polymedication. The aim of our purpose was to investigate whether a genetic factor, such as cyp2c9 genotype, does influence the warfarin maintenance dose in very elderly patients. METHODS: In-patients treated with warfarin were recruited with the following inclusion criteria: i/ 75 years-old or over; ii/ a stable INR within the therapeutic range (INR 2.0-3.0). Genotypes were coded as numbers of alleles for each of the three polymorphisms, namely 2C9*1 (wild-type), 2C9*2, and 2C9*3. RESULTS: CYP2C9 genotype was performed in 126 patients, mean age 87 +/-6 years (75-103), 29 males-97 females. The mean daily dose of warfarin was 3.0 +/-1.4 mg, with 3.1 mg in patients with the wild-type *1/*1 genotype (n =80), 2.7 mg in *1/*2 heterozygotes (n =20), 2.9 mg in *1/*3 heterozygotes (n =18), 1.2 mg in *2/*2 homozygotes (n =2), 2.3 mg in compound heterozygotes *2/*3 (n =6). The relationships between dose and potential factors were assessed using the correlation coefficient test for age and Fischer exact tests for the categorical variables. The only factors significantly linked to the dose were the numbers of 2C9*1 and 2C9*2 alleles. CONCLUSION: In elderly patients, a genetic influence on response to warfarin does exist as in younger patients.

Age Factors↗
PubMed2026

Unraveling the genomic blueprint of the Indian black soldier fly: From genome assembly to evolutionary insights.

The black soldier fly (BSF) (Hermetia illucens) has been renowned for its sustainable bioconversion capabilities, resulting in smart protein production with wide applications in animal feed, bioenergy, and biofertilizer. However, the genetic mechanisms underlying efficient bioconversion and productivity remain poorly understood. To advance strain-specific applications and strengthen genetic resource availability, we present the whole genome sequencing (WGS) data for an Indian isolate of black soldier fly. The assembled genome was 1.46 Gb with a scaffold N50 of 172.7 Mb, and a GC content of 42.6%. Furthermore, 64.17% of genomic sequences were masked as repeated, and 14,317 protein-coding sequences were identified. Variant analysis against the reference genome identified 34.44 million variants (∼33.25 million SNPs and ∼ 1.18 million INDELs), with the majority (99.3%) classified as MODIFIER, 0.54% as LOW impact, 0.14% as MODERATE, and only 0.003% as HIGH impact. Comparative genomic analysis with other related species revealed expansions of gene families in BSF associated with Immune effector (Antimicrobial peptides (AMPs), Lysozymes, and Peptidoglycan Recognition Protein (PGRP) and Detoxification (cytochrome P450 enzymes). Notably, AMPs in the Indian isolate showed enhanced copy number variation in defensin (27) and PGRP (40) compared to reference BSF, suggesting potential regional adaptations to pathogen exposure. Collectively, this genomic data provides an improved resource for evolutionary studies, functional genomics, and targeted genetic improvement of BSF for sustainable bioconversion applications.

Comparative genomics↗
PubMed2000

The human growth hormone receptor gene - characterisation of the liver-specific promoter.

Several variants (V1-V8) have been described for the 5' untranslated region of human growth hormone receptor cDNA (Pekhletsky, R.I., Chernov B.K., Rubtsov, P.M., 1992. Variants of the 5'-untranslated sequence of human growth hormone receptor mRNA. Mol. Cell. Endocrinol. 90, 103-109). Transcription of one of these, variant V1, is under the control of a liver-specific promoter (Zou, L., Burmeister L.A., Sperling, M.A., 1997. Isolation of a liver-specific promoter for human growth hormone receptor gene. Endocrinology 138, 1771-1774). Further characterisation of this promoter shows that: (1) a cluster of exon 1 variants, which includes that coding for V1, is located about 13 kb upstream of the first coding exon; (2) the human V1 promoter (and not V7, as previously suggested) is homologous to liver-specific regulatory regions of rat and mouse GH receptor genes; (3) the transcription start site for V1 is 27 bp further upstream than previously reported; (4) a 158-bp sequence is sufficient for basal promoter activity, while larger constructs provide evidence for negative elements further upstream; and (5) nuclear proteins from HepG2 hepatoma cells protect regions of the V1 promoter from DNase digestion, revealing putative regulatory sites.

5' Untranslated Regions↗