Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “coding variants”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed1985

Trypanosoma brucei: the extent of conversion in antigen genes may be related to the DNA coding specificity.

The boundaries of gene conversion in variant-specific antigen genes have been determined in six clones of Trypanosoma brucei. In each clone, antigenic switching involved interaction between two telomeric members of the AnTat 1.1 multigene family, which share extensive homology throughout their coding regions. All conversion events occurred by substitution of faithful copies of donor sequences. Conversion endpoints were nonrandomly distributed. In four clones, the 5' conversion limit was near the antigen translation initiation codon, while in three clones, the 3' conversion limit was located at the "hinge" between the two major antigen domains. In one case, two segmental conversions were involved in antigen switching. These observations reveal that antigen gene conversion can occur without generating point mutations, and suggest that postrecombinational selection may impose a limit on the number of possible rearrangements within antigen genes.

Amino Acid Sequence↗
PubMed1980

Cloning and characterization of DNA sequences complementary to messenger ribonucleic acids coding for the synthesis of two surface antigens of Trypanosoma brucei.

Full length double-stranded complementary DNAs (ds cDNAs) could be synthesized on mRNAs enriched in sequences coding for the synthesis of the variant specific antigens (VSAs) AnTat 1.1 and AnTat 1.8 from Trypanosoma brucei brucei. The size of these ds cDNAs is about 1700 and 1850 base pairs for AnTat 1.1 and AnTat 1.8 respectively. The ds cDNAs were cloned in the plasmid pBR322; two clones harboring a copy of each coding sequence were selected. Both the hybrid-arrested translation and the positive hybridization elution methods confirmed that these recombinants contain VSA-specific inserts. A restriction map was constructed in each case. The two sequences seem to be inserted in a reversed 3'--5' orientation, respective to the plasmid polarity. The AnTat 1.8 cloned sequence is a palindrome probably due to a cloning artefact. Hybridization of the cloned DNAs with "Northern" blots of total or poly(A)+ RNA revealed in each case a single, specific band. The expression of these VSA genes appears thus to be regulated at the transcriptional level.

Antigens, Surface↗
PubMed2026

Predicting genome-wide functional constraints with GPN-Star.

Genomic language models have emerged as a powerful approach for learning genome-wide functional constraints directly from DNA sequences1. However, standard genomic language models adapted from natural language processing often require large model sizes and computational resources, yet still fall short of classical evolutionary models in predictive tasks2-4. Here we introduce a genomic pretrained network with species tree and alignment representations (GPN-Star), which is a biologically grounded genomic language model featuring a phylogeny-aware architecture that leverages whole-genome alignments and species trees to model evolutionary relationships explicitly. Trained on alignments spanning vertebrate, mammal and primate evolutionary timescales, GPN-Star achieves state-of-the-art performance across a wide range of variant effect prediction tasks in both coding and non-coding regions of the human genome. Analyses across timescales show task-dependent advantages of modelling more recent versus deeper evolution. To demonstrate its potential to advance human genetics, we show that GPN-Star substantially outperforms previous methods in prioritizing pathogenic and fine-mapped genome-wide association study variants, yields strong enrichments of complex trait heritability and improves power in rare variant association testing5. Extending beyond humans, we train GPN-Star for five model organisms-Mus musculus, Gallus gallus, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana-demonstrating the robustness and generalizability of the framework. Taken together, these results position GPN-Star as a scalable, powerful and flexible tool for genome interpretation, well suited to leverage the growing abundance of comparative genomics data.

Journal Article↗
PubMed1981

Field testing of consumer safety signs: the comprehension of pictorially presented messages.

This paper describes one of a series of studies on the investigation of desirable characteristics of a labelling system for use on potentially dangerous household products. The suitability of a range of signs based on symbolic coding of hazards has been investigated. The hazards investigated were: Fire, Poison, Caustic, Electrical and General. The first stage of the programme involved a survey of all known symbols used for these and similar applications, followed by some preliminary testing to determine a range of symbols for more detailed testing. This subsequent testing of the symbols involved their incorporation into a range of sign variants, with differing colours of image and background together with variations in the shape and colour of enclosure containing symbol. These symbolically coded sign variants were tested in the field using a structured national random sample of 4000 respondents. The data were analyzed using a variable, but systematically controlled, criterion for correct comprehension, which allowed reliable discrimination between certain of the sign variants in terms of comprehension performance. In absolute terms, comprehension of even the best of the signs was not markedly high, ranging from around 20% with s stringent criterion up to 50% if a less stringent criterion of correct comprehension was used. Some of the poorer signs tested failed to achieve better than 5% correct comprehension rate even with a lax criterion for comprehension. Prior experience of the sign was found to enhance comprehension, increasing the correct comprehension rate by a factor of 1.5-2.0 times the correct comprehension rates obtained with those respondents who affirm that they have not seen the sign before.

Journal Article↗
PubMed1999

Cloning of the human phospholipase A2 activating protein (hPLAP) gene on the chromosome 9p21 melanoma deleted region.

Cutaneous malignant melanoma (CMM) is a common skin cancer. About 50% of CMM sporadic tumours have lost one copy of the chromosome 9p21 region. To identify genes involved in the initiation and/or progression of CMM we have characterised the 9p21 melanoma deleted region and screened the human expressed sequence tag (EST) databases (dbEST) to search for expressed genes. We have identified the gene that encodes the human orthologue of the rat phospholipase A2 activating protein (PLAP). PLAP was considered a potential candidate to be involved in malignant melanoma because it maps to the critical region for CMM and because the PLA2 gene has been identified as a modifier of the APC gene, responsible for the adenomatous polyposis phenotype in the mouse. PLAP encodes a protein of 738 amino acids and has a high DNA (90%) and protein (97%) sequence similarity with the rat and mouse PLAP protein. PLAP has a region of WD40 repeats in the amino-terminus, which allows us to include this protein in the superfamily of beta-transducin proteins. Northern blot hybridisation gave a fragment of 4.5 kb, with higher expression in heart compared to other tissues. PLAP was localised at chromosome 9p21, between marker AFM218xg11 and TEK. SSCP analysis of the coding region of PLAP revealed no variants in the studied samples, but one of six CMM samples analysed by RT-PCR showed specific inactivation of PLAP. Despite PLAP's important role in mediating several cellular responses and its localisation to the chromosome 9p21 region deleted in CMM, it is unlikely that point mutations or deletions in the coding region of PLAP are responsible for the initiation or progression of CMM. Further studies on PLAP inactivation should be performed to clarify its potential involvement in CMM.

Amino Acid Sequence↗
PubMed1995

Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments.

Human papillomavirus type 16 (HPV16) nucleotide sequence variations in the E6 (nucleotide positions [nt] 104 to 559), L2 (nt 4272 to 5657), and L1 (nt 5665 to 7148) open reading frames (ORFs), and the long control region (nt 7479 to 7842), were examined in 29 selected United States isolates. Of 3,690 nucleotide positions, 129 (3.5%) varied. The maximum pairwise distance was 66 nucleotide differences, or 1.8%. Nucleotide variations within different genome segments were phylogenetically compatible, and nucleotide changes within E6, L2, and L1 contained phylogenetic information beyond that provided in the long control region. Most isolates were classified as members of HPV16 lineages that have been described previously. However, two novel phylogenetic branches were identified. The L2 ORF was the most variable coding segment. L2 synonymous and nonsynonymous nucleotide changes were distributed asymmetrically. The amino-terminal half of the L2 protein was remarkably conserved among all isolates, suggesting that the region is under evolutionary constraint. The amino-terminal region of the E6 ORF was relatively varied, especially at E6 amino acid positions 10 and 14. Several amino acid difference in the L1 ORF were observed between lineages. Forty-nine amino acid variations across all sequenced coding regions were observed. These amino acid differences may be relevant to differences in the generation of humoral or cell-mediated immune responses to HPV16 variants. Our data form a basis for considering HPV16 sequence variation in the rational design of vaccine strategies and as an epidemiologic correlate of cervical cancer risk.

Amino Acid Sequence↗
PubMed1993

Cloning of human transketolase cDNAs and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals.

Variants of the enzyme transketolase which possess reduced affinity for its cofactor thiamine pyrophosphate (high apparent Km) have been described in chronic alcoholic patients with Wernicke-Korsakoff syndrome. Since the syndrome has been shown to be directly related to thiamine deficiency, it has been hypothesized that such transketolase variants may represent a genetic predisposition to the development of this syndrome. To test this hypothesis, human transketolase cDNA clones were isolated, and their nucleotide and predicted amino acid sequence were determined. Transketolase was found to be a single copy gene which produces a single mRNA of approximately 2100 nucleotides. Additionally, the nucleotide sequence of the transketolase coding region in fibroblasts derived from two Wernicke-Korsakoff (WK) patients was compared to that of two nonalcoholic controls. Although nucleotide and predicted amino acid differences were detected between fibroblast cultures and the original cDNAs and among the cultures themselves, no specific nucleotide variations, which would encode a variant amino acid sequence, were associated exclusively with the coding region from WK patients. Thus, allelic variants of the transketolase gene cannot account for the biochemically distinct forms of the enzyme found in these patients nor be considered as a mechanism for genetic predisposition to the development of Wernicke-Korsakoff syndrome. Instead, the underlying mechanism must be extragenic and may be a result of differences in post-translational processing/modification of the transketolase polypeptide.

Alcohol Amnestic Disorder↗
PubMed2026

Genome-Wide and Rare Variant Association Studies of Amblyopia in Admixed American and African Ancestry Groups.

OBJECTIVE: To identify genetic variants associated with amblyopia in African (AFR) and Admixed American (AMR) ancestry groups, expanding on previous studies conducted in European ancestry. DESIGN: Retrospective ancestry-stratified genome-wide association study (GWAS) and gene-level rare variant association study (RVAS). PARTICIPANTS: Participants in the All of Us Research Program from AFR and AMR ancestry groups who had whole-genome sequencing available. Cases and controls were distinguished based on the presence of International Classification of Diseases 9/10/SNOMED diagnosis codes for amblyopia in electronic health records. This yielded ancestry-stratified subsets of 269 cases and 71 585 controls of AMR ancestry and 366 cases and 79 460 controls of AFR ancestry. METHODS: Stratified logistic regression models were adjusted for age, biological sex, and the top 10 principal components of genomic ancestry. GWAS was limited to common variants (minor allele frequency &#x2265;1%), and RVAS was limited to rare variants with coding sequence-altering effects (minor allele frequency >1%, exonic only, excluding synonymous variants) aggregated at the gene level using the SKAT algorithm. Downstream analyses of the significant variants were performed using KEGG and GO pathway analysis and STRING database queries for protein-protein interactions and gene-gene interactions. MAIN OUTCOME MEASURES: Single-nucleotide polymorphisms were determined to have genome-wide significance if P < 5e-8 in the GWAS, and genes were determined to have significant association with amblyopia in the RVAS if P < 8.0 &#xd7; 10-4. RESULTS: In the AMR GWAS, 245 unique single-nucleotide polymorphisms mapping to 97 distinct loci were identified, notably within neurodevelopmental and axonal guidance genes, including ROBO1, SEMA4B, PTPRD, NRXN1, and CAMK2D. The AFR GWAS identified 11 significant variants corresponding to 6 loci mapping primarily to long noncoding RNAs and pseudogenes. The AMR RVAS identified 15 genes, including axonal transport genes (KIF1B and KIF7) and growth factor signaling genes (EGF, ERBIN, and AKAP17A). The AFR RVAS identified a single gene, DLG2, which encodes the postsynaptic protein PSD-93, which promotes the closure of the sensitive period of neuroplasticity for vision in early childhood. CONCLUSIONS: Genetic risk architectures for amblyopia differ across ancestries but fundamentally converge on neurodevelopmental signaling, cortical synapse assembly, and sensitive period plasticity rather than ocular structural dynamics. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Amblyopia↗
PubMed2002

Calpain 10 and genetics of type 2 diabetes.

Positional cloning studies conducted on a region of chromosome 2q providing evidence for linkage to type 2 diabetes implicated genetic variation at the calpain-10 gene (CAPN10) in susceptibility to type 2 diabetes. The variants identified in these studies are located in introns, rather than in coding sequence. It was proposed that the cumulative effects of a combination of variants, rather than variation at a single site, increase the risk of type 2 diabetes. Confirmation of the hypothesis that non-coding sequence variation in CAPN10 affects susceptibility to type 2 diabetes has implications for how we search for susceptibility variants and interpret results of positional cloning studies for complex disorders, and suggests a new pathway in glucose homeostasis. We review the results of follow-up studies on the CAPN10 finding, and consider the issues inherent in conclusively establishing that particular genetic variation affects a complex phenotype.

Calpain↗
PubMed1998

Expression of an embryonic fibronectin splicing variant in human masseter muscle.

Fibronectin is an extracellular matrix protein that is a key constituent of all skeletal muscles. Its deposition increases in a number of pathological conditions, including some muscular dystrophies in which a progressive increase in lower-face height is often noted. It has been shown in other organ systems that increased deposition of fibronectin is associated with changes in the expression of differentially spliced isoforms of the molecule. This investigation documents the expression of mRNA coding for fibronectin and its splicing variants, EIIIA and EIIIB, in biopsies of masseter muscle from normal and long-face patients, using reverse transcriptase-polymerase chain reaction. Expression was compared with that occurring in anatomically and embryologically differing somatic skeletal muscle. Masseter expressed fibronectin mRNA containing the EIIIA but not the EIIIB splicing variant. Conversely, somatic skeletal muscle expressed neither the EIIIA nor EIIIB variants. There were no differences between expression of fibronectin containing the EIIIA splicing variants in masseter from normal and long faces. These results suggest that variations in fibronectin expression reflect the differing functional demands of muscles from different anatomical locations and indicate that jaw and somatic muscle belong to different allotypes.

Base Sequence↗
PubMed2003

BRAF as a melanoma susceptibility candidate gene?

A high frequency of activating BRAF somatic mutations have been identified recently in malignant melanoma and nevi indicating that BRAF activation could be an early and critical step in the initiation of melanocytic neoplasia. To determine whether BRAF mutations could be an earlier event occurring at the germline level, we screened the entire BRAF coding region for germline mutations in 80 independent melanoma-prone families or patients with multiple primary melanoma without a familial history. We identified 13 BRAF variants, 4 of which were silent mutations in coding regions and 9 nucleotide substitutions in introns. None of these BRAF variants segregated with melanoma in the 11 melanoma families studied. Moreover, there was no significant difference in the frequency of heterozygotes for BRAF variants between melanoma cases and controls when they were compared. Our data suggest that BRAF is unlikely to be a melanoma susceptibility gene.

Chromosome Segregation↗
PubMed2001

New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes.

We investigated the significance of the variants of the IRS-2 gene in patients with type 2 diabetes. The entire coding part of the IRS-2 gene was screened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IRS-2 gene with type 2 diabetes was studied in 85 Finnish diabetic patients and 82 Finnish control subjects and in 100 Chinese diabetic patients and 85 Chinese control subjects. The four variants predicting structural changes in the insulin receptor substrate (IRS)-2 protein included an insertion of AAC (Asn) in the Asn repeat sequence centered around codons 29-36 (allele frequencies of 0 vs. 0.6% and 1.5 vs. 0%), the Ala157Thr substitution (0 vs. 0% and 0.5 vs. 0%), the Leu647Val substitution (0.6 vs. 0% and 0 vs. 0%), and the Gly1057Asp polymorphism (31 vs. 31% and 35 vs. 30%) (P = NS for all comparisons). Furthermore, six silent variants were observed (CGC147CGG, CCC155CCG, GCC156GCT, AGT723AGC, TGT816TGC, and CCC829CCT). The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose tolerance (n = 295) or impaired glucose tolerance (n = 38). These data indicate that structural variants of the IRS-2 gene were uncommon in Finnish and Chinese patients with type 2 diabetes. Thus, the variants in the coding part of the IRS-2 gene are unlikely to have a major role in the development of type 2 diabetes in Finnish or Chinese subjects.

Age of Onset↗
PubMed1987

Identification of a cDNA coding for a fifth form of myelin basic protein in mouse.

The primary sequences of four molecular mass variants (14, 17, 18.5, and 21.5 kDa) of the mouse myelin basic protein (MBP) have recently been determined through analysis of cDNA clones of their mRNAs. The mRNAs coding for the four MBP variants are thought to arise by differential splicing of two exons (exons 2 and 6) from a single gene. In contrast, exons 2 and 5 may be spliced out in the posttranscriptional processing of the human MBP gene. To investigate the possibility that a third exon (exon 5) may also be differentially spliced out in the processing of the mouse MBP gene transcript, a mouse cDNA library was screened to search for cDNAs missing exon 5. A MBP cDNA was isolated whose coding region specified a fifth mouse MBP variant with a molecular mass of approximately equal to 17 kDa. The mass of this variant (17,257 Da) is so close to that of the other 17-kDa mouse MBP (17,224 Da) that the two would be indistinguishable on NaDodSO4/polyacrylamide gels. Analysis of the sequence of the cDNA clone indicates that excision of exons 2 and 5 of the mouse MBP gene would produce the mRNA encoding this newly described 17-kDa MBP, whereas excision of exon 6 would produce the mRNA for the other 17-kDa MBP variant. Thus, the "17-kDa" mouse MBP consists of at least two molecular forms with very similar molecular masses but markedly different primary sequences. Of five full-length or near full-length cDNAs representing 17-kDa MBPs, one was missing exons 2 and 5 and four were missing exon 6.

Amino Acid Sequence↗
PubMed1996

Glucokinase gene variants in Chinese subjects with the common form of NIDDM.

OBJECTIVE: To determine whether mutation of the coding or junction region of glucokinase gene (GCK) is also the pathogenic cause of the common form of non-insulin-dependent diabetes mellitus (NIDDM) in Chinese. METHODS: Single strand conformation polymorphism (SSCP) analysis was performed after the 12 exons and junction regions of GCK of each subject studied were separately amplified with polymerase chain reaction (PCR). The molecular scanning was carried out in 30 Chinese subjects with common form NIDDM having the age of onset at or before 45 years, and/or with positive family history of diabetes mellitus (NIDDM-A group). Further screening of the mutation/variation found was conducted in 56 NIDDM subjects (NIDDM-B group) and 134 non-diabetes subjects (ND group) in order to define their frequencies. RESULTS: No mutation was found by molecular scanning in coding or junction region of GCK in NIDDM-A group. A variant of intron I b was detected in GCK of NIDDM subjects, especially in those with early age of onset and/or with positive family history of diabetes. Significant difference in incidences was found between ND group and NIDDM-A+B group (0% vs 4.7%, Fisher exact P = 0.022). CONCLUSIONS: (1) Mutation of coding and junction regions of GCK is not the main pathogenic factor of common form NIDDM in Chinese subjects. (2) A variant of GCK intron I b may be found in NIDDM in Chinese, especially in those with early age of onset and/or with positive family history of diabetes. Its role in the expression of GCK remain to be elucidated.

Adult↗
PubMed2000

Expression of multiple plasma membrane Ca(2+)-ATPases in rat pancreatic islet cells.

When stimulated by glucose, the pancreatic beta-cell displays large oscillations of intracellular free Ca2+ concentration ([Ca2+]i). To control [Ca2+]i, the beta-cell must be equipped with potent mechanisms for Ca2+ extrusion. We studied the expression of the plasma membrane Ca(2+)-ATPases (PMCA) in three insulin secreting preparations (a pure beta-cell preparation, RINm5F cells and pancreatic islet cells), using reverse-transcribed PCR, RNase protection assay and Western blotting. The four main isoforms, PMCA1, PMCA2, PMCA3 and PMCA4 were expressed in the three preparations. Six alternative splice mRNA variants, characterized at splice sites A, B and C were detected in the three preparations (rPMCA1xb, 2yb, 2wb, 3za, 3zc, 4xb), plus two additional variants in pancreatic islet cells (PMCA4za, 1xkb). The latter variant corresponded to a novel variant of rat PMCA1 gene lacking the exon coding for the 10th transmembrane segment, at splice site B. At the mRNA and protein level, five variants predominated (1xb, 2wb, 3za, 3zc, 4xb), whilst one additional isoform (4za), predominated at the protein level only. This provides the first evidence for the presence of PMCA2 and PMCA3 isoforms at the protein level in non-neuronal tissue. Hence, the pancreatic beta-cell is equipped with multiple PMCA isoforms with possible differential regulation, providing a full range of PMCAs for [Ca2+]i regulation.

Actins↗
PubMed1996

BRCA2 germline mutations in male breast cancer cases and breast cancer families.

The breast cancer susceptibility gene, BRCA2 on chromosome 13q12-13, was recently isolated. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as wall as a proportion of inherited ovarian cancer. Many BRCA2-linked families also contain cases of male breast cancer. We have analysed germline DNA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast-ovarian cancer families for mutations in BRCA2. All 17 breast-ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplified DNA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al. in this issue that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified -- all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; for thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.

BRCA2 Protein↗
PubMed1989

Alpha-amanitin resistant transcription of protein coding genes in insect and bloodstream form Trypanosoma brucei.

The variant cell surface glycoprotein (VSG) gene expression sites of the protozoan Trypanosoma brucei are transcribed by an unusual alpha-amanitin resistant RNA polymerase. All other protein coding genes of T.brucei examined to date are transcribed by an alpha-amanitin sensitive RNA polymerase, presumably RNA polymerase II. We now show that transcription of protein coding genes by alpha-amanitin resistant RNA polymerases is not unique to the bloodstream form expressed VSG gene expression sites, but also occurs in insect form trypanosomes, which do not express VSG genes. In insect form trypanosomes transcription of the procyclin or PARP genes is resistant to alpha-amanitin to a degree comparable with that of VSG and ribosomal RNA (rRNA) genes. Comparison of the alpha-amanitin resistantly transcribed PARP and VSG gene families shows that they both produce one of the most abundant mRNAs [1-3% of poly(A)+] and they both encode the major cell surface proteins of their respective life cycle stages. Transcription of a subset of functionally comparable protein coding genes is thus mediated by an RNA polymerase which differs from the regular RNA polymerase II.

Amanitins↗
PubMed1994

Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants.

Human microsomal epoxide hydrolase (mEH) is a biotransformation enzyme that metabolizes reactive epoxide intermediates to more water-soluble trans-dihydrodiol derivatives. We compared protein-coding sequences from six full-length human mEH DNA clones and assessed potential amino acid variation at seven positions. The prevalence of these variants was assessed in at least 37 unrelated individuals using polymerase chain reaction experiments. Only Tyr/His 113 (exon 3) and His/Arg 139 (exon 4) variants were observed. The genotype frequencies determined for residue 113 alleles indicate that this locus may not be in Hardy-Weinberg equilibrium, whereas frequencies observed for residue 139 alleles were similar to expected values. Nucleotide sequences coding for the variant amino acids were constructed in an mEH cDNA using site-directed mutagenesis, and each was expressed in vitro by transient transfection of COS-1 cells. Epoxide hydrolase mRNA level, catalytic activity, and immunoreactive protein were evaluated for each construct. The results of these analyses demonstrated relatively uniform levels of mEH RNA expression between the constructs. mEH enzymatic activity and immunoreactive protein were strongly correlated, indicating that mEH specific activity was similar for each variant. However, marked differences were noted in the relative amounts of immunoreactive protein and enzymatic activity resulting from the amino acid substitutions. These data suggest that common human mEH amino acid polymorphisms may alter enzymatic function, possibly by modifying protein stability.

Amino Acid Sequence↗