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 1,801 records · Page 100Linked to original sources
PubMed1998

Production of rat salivary cystatin S variant polypeptides in Escherichia coli.

Cystatins are protein inhibitors of papain and related cysteine proteinases. A series of continuous synthetic peptides corresponding to the entire sequence of rat salivary cystatin was used to localize the binding domains of the cystatin to papain. Several synthetic peptides, one from the aminoterminal sequence (peptide 1-24) and others from the carboxylterminal (peptides 66-79, 66-90, 79-90, 79-114), showed binding to papain, but none of the peptides showed inhibition of papain activity. Three recombinant rat salivary cystatin variants (N-terminal truncated protein lacking amino acid residues 1-9; variant 49-53, in which amino acid residues QVVAG of rat salivary cystatin had been replaced with amino acid residues LVL in mutant protein; and variant 65-78, in which amino acid residues 65-78 had been replaced with amino acids PG in mutant protein) were produced using the Escherichia coli expression system pGex-4T. To generate N-terminal truncated protein the desired coding region of the cystatin gene was amplified by polymerase chain reaction (PCR). To produce the variants 49-53 and 65-78, a PCR-based approach of gene splicing by overlap extension was used. Recombinant cystatin proteins were produced as insoluble inclusion bodies as fusion proteins with a glutathione S-transferase (GST) carrier. After solubilization with urea the GST carrier was cleaved from the fusion protein with thrombin and cystatin variants purified by fast liquid chromatography on a MonoQ column. The purified proteins reacted with antibodies to rat salivary cystatin. The N-terminal truncated and variant 49-53 exhibited very little inhibitory activity towards papain, whereas variant 65-78 exhibited papain-inhibitory activity similar to the full-length recombinant cystatin.

Alternative Splicing↗
PubMed2006

Sporadic ALS is not associated with VAPB gene mutations in Southern Italy.

Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu) was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS.

Adult↗
PubMed2003

Decreased function of genetic variants, Pro283Leu and Arg287Gly, in human organic cation transporter hOCT1.

We have evaluated the functional consequences of genetic variations in human organic cation transporter hOCT1 (SLC22A1). Three coding single nucleotide polymorphisms (cSNPs) resulted in the amino acid changes Pro283Leu, Arg287Gly and Pro341Leu were assessed. Uptake experiments with transient expression system using HEK293 cells revealed that the variants Pro283Leu and Arg287Gly had completely diminished transport activity. The other variant Pro341Leu had a significantly, but not completely, decreased transport activity. Western blot analysis showed that the expression levels of all three variant proteins in the crude membranes of HEK293 cells were comparable to those of wild type hOCT1. Moreover, the expression of variant proteins at the plasma membrane was confirmed by indirect immunofluorescence, indicating that these SNPs did not affect the membrane localization of hOCT1. Present results suggest that the amino acid residues Pro283 and Arg287 have a substantial role in substrate recognition of hOCT1.

Journal Article↗
PubMed1994

Soybean dwarf luteovirus contains the third variant genome type in the luteovirus group.

Complementary DNAs covering the entire RNA genome of soybean dwarf luteovirus (SDV) were cloned and sequenced. Computer analysis of the 5861 nucleotide sequence revealed five major open reading frames (ORFs) possessing conservation of sequence and organisation with known luteovirus sequences. Comparative analyses of the genome structure show that SDV shares sequence homology and features of gene organisation with barley yellow dwarf virus (PAV isolate) in the 5' half of the genome, yet is more closely related to potato leafroll virus in its 3' coding regions. In addition, SDV differs from other known luteoviruses in possessing an exceptionally long 3' terminal sequence with no apparent coding capacity. We conclude from these data that the SDV genome represents a third variant genome type in the luteovirus group.

Amino Acid Sequence↗
PubMed1997

Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity.

Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3 +/- 8.4 kg/m2). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa[k]/ fa[k]) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85%, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 +/- 6.5 kg/m2) and 68 non-obese (BMI 21.6 +/- 2.2 kg/m2) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects.

Adolescent↗
PubMed1999

Multiple causes of size variation in the diploid megabase chromosomes of African tyrpanosomes.

The chromosomes of many protozoans are polymorphic in size, but African trypanosomes contain diploid homologues which are exceptionally size-polymorphic. We present the first complete analysis of the structure of a Trypanosoma brucei megabase chromosome which reveals the concentration of repetitive sequence, non-random distribution of transposon-like elements, and a hemizygous variant surface glycoprotein gene expression site. Subsequent comparative analyses of size-polymorphic homologues show that the repetitive regions are highly polymorphic, as demonstrated in studies on the chromosomes of other protozoan parasites. We show that a large number of the transposon-like elements are located in these regions. However, although we have shown elsewhere that synteny is maintained in coding regions, homologous chromosomes may vary along their entire length. Thus, the variable chromosomal location of variant surface glycoprotein expression gene sites, the expansion and contraction of repetitive DNA, the number of putative transposons, sequence polymorphism at chromosome ends, and expansion and contraction within or between coding regions all contribute to huge chromosomal size polymorphisms in T brucei.

Animals↗
PubMed1997

Human tenascin-C: identification of a novel type III repeat in oral cancer and of novel splice variants in normal, malignant and reactive oral mucosae.

Tenascin-C is a mosaic, linear glycoprotein that is up-regulated during many normal and pathological processes involving either cell migration or tissue morphogenesis, such as invasion of malignant cells and wound healing. Human tenascin-C contains 8 consecutive type III fibronectin (TNCfn) domains that are involved in alternative splicing and potentially generate a large number of isoforms that code for tenascin-C proteins with subtly different functions. Human tenascin-C splice variants were investigated by RT-PCR in a range of normal and pathological oral mucosal tissues. A novel, 9th human TNCfn domain involved in alternative splicing was identified. It shares 70% nucleic acid and 55% protein sequence homology with chicken TNCfn-ad2. As in avians, this novel repeat was located between TNCfn-B and TNCfn-ad1 and accordingly was designated human TNCfn-ad2. Human TNCfn-ad2 was detected in only 2 of 10 oral cancers. However, TNCfn-ad2 was absent from 40 normal, reactive, pre-malignant and other oral mucosal specimens investigated. Previous studies have described 8 splice variant transcripts for human tenascin-C. By systematic investigation we identified further novel splice variants for human tenascin-C. Furthermore, our results indicate that many potential splice variants probably do not exist in the tissues investigated. Thus, we have demonstrated that human tenascin-C transcripts generate a complex but selected repertoire of different alternative splice products.

Alternative Splicing↗
PubMed1995

Alternative mRNAs encode multiple isoforms of transcription factor AP-2 during murine embryogenesis.

Transcription factor AP-2 has been implicated as an important regulator of gene expression during vertebrate embryogenesis. We report here the cDNA cloning and analysis of mouse embryonic mRNA splice variants encoding four AP-2 isoforms. Isoform 1 is the homolog of the previously known human (HeLa) AP-2. The three new AP-2 isoforms all share the same DNA binding/dimerization domain as isoform 1 but either lack the proline-rich transcriptional activation domain encoded by exon 2 (isoform 2) or have different amino-termini encoded by two previously unknown alternative first coding exons for AP-2 (isoforms 3 and 4). All four AP-2 mRNA variants are present at significant levels between Days 11.5 and 17.5 of mouse embryogenesis. Variants 1, 3, and 4 show qualitatively but not quantitatively similar restricted expression patterns in 8.5-12.5 dpc embryos examined by in situ hybridization. At mid-embryogenesis, variant 3 is the major AP-2 mRNA species in the nervous system and in total embryo RNA but is less prevalent than variants 1 and 4 in the epidermis. The four mRNAs are all induced, although unequally, during differentiation of P19 cells into neural cell types and by cAMP stimulation of primary astrocytes. Variants 1-3 are coexpressed in different ratios in HeLa cells and in three human glioblastoma cell lines. These findings reveal that transcriptional regulation by AP-2 is likely to be more complex than previously assumed given the potential for multiple AP-2 homo- and heterodimeric DNA binding forms.

Alternative Splicing↗
PubMed1996

The production and characterization of artificial heterodimers of the restriction endonuclease EcoRV.

A novel approach to studying the inter- and intrasubunit communication required for the activity of homodimeric proteins is described. It was developed for the restriction endonuclease EcoRV, but should also be useful for other homodimeric enzymes. Two ecorV genes encoding different EcoRV mutants are coexpressed in the same Escherichia coli cell leading to homo- and heterodimeric variants of the enzyme. The two ecorV genes carry either a 5' extension coding for the glutathione-S-transferase or a His6-tag. The EcoRV heterodimer produced in vivo is separated from the two EcoRV homodimers and purified to homogeneity by affinity chromatography. Purified EcoRV heterodimers are stable and are not subject to reassortment of the subunits. To investigate the interdependence of the two catalytic centers, EcoRV heterodimers consisting of one subunit with wild type sequence and one subunit with amino acid substitutions in the PD...(D/E)XK motif, characteristic for the active sites of many restriction endonucleases, were produced. While the homodimeric EcoRV active site mutants are catalytically inactive, the heterodimeric EcoRV variants with one active and one inactive catalytic center display a twofold reduced activity toward oligodeoxynucleotide substrates compared to the wild type, and preferentially nick supercoiled plasmid DNA. From these results we conclude that in the wild type enzyme both catalytic centers function independently of each other.

Biopolymers↗
PubMed1995

A multiple site-specific DNA-inversion model for the control of Omp1 phase and antigenic variation in Dichelobacter nodosus.

The molecular cloning and sequence analysis of four structurally variant linked genes (omp1A,B,C,D) that encode the major outer membrane protein of Dichelobacter nodosus strain VCS1001 are described. The isolation of rearranged copies of omp1A and omp1B, and the identification in the 5' regions of all four genes of short cross-over-site sequences that were similar to the Din family of cross-over-site sequences, suggested that site-specific DNA inversion was involved in omp1 rearrangement. Evidence for site-specific inversion of the 497 bp DNA fragment, which was located between the divergently orientated omp1A and omp1B genes, and which contained the promoter and 5' coding sequence of Omp1, was obtained by polymerase chain reaction-mediated amplification of inverted forms of these genes. However, to account for all of the omp1 gene copies cloned in this study, a more widespread inversion phenomenon must be involved in the rearrangement of these genes and a model for multiple site-specific DNA inversions at the omp1 locus is described. In this model the four structurally variant omp1 genes can be assembled from one of four structurally variant C-terminal coding regions and a conserved N-terminal coding region and can be expressed from a single promoter. It is postulated that this genetic capability endows D. nodosus with the ability to switch the antigenic specificity of one of its major surface proteins.

Amino Acid Sequence↗
PubMed2004

Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus.

Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.

Animals↗
PubMed2005

The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density.

BACKGROUND: A 40-bp variable number of tandem repeats (VNTR) polymorphism exists in the 15th exon of DAT1, the gene encoding the human dopamine transporter (DAT). Though the VNTR resides in a region encoding the 3' untranslated region (UTR) and does not alter the protein's amino acid sequence, the prevalent 10-repeat variant has shown both linkage and association to Attention Deficit Hyperactivity Disorder (ADHD). In this study, we examined the effects of the DAT1 VNTR on measures of in vitro DAT expression and pharmacology. A series of four DAT1 constructs, each containing the DAT1 coding region, but varying with respect to the downstream presence or content of the 3'UTR, were engineered and stably transfected into an HEK-293 variant using Flp-In integration, an enzyme-mediated, site-specific recombination technology. RESULTS: [3H] Win 35,428 saturation binding assays and DAT immunoblots revealed statistically significant differences in DAT expression attributable to DAT1 genotype. Cells harboring the 10-repeat DAT1 variant were characterized by a Bmax approximately 50% greater than cells with the 9-repeat VNTR; those containing only the DAT1 coding region or the coding region flanked by a truncated 3' UTR resulted in greater DAT density than either of the naturalistic 9- and 10-repeat variants. Competition binding assays showed no statistically significant DAT1 genotype effects on the DAT affinity for methylphenidate, a finding consistent with the positional location of the VNTR. CONCLUSION: This study identified the DAT1 VNTR as a functional polymorphism and provides an interpretive framework for its association with behavioral phenotypes.

Attention Deficit Disorder with Hyperactivity↗
PubMed1989

Apolipoprotein E-1Harrisburg: a new variant of apolipoprotein E dominantly associated with type III hyperlipoproteinemia.

Apolipoprotein E (apoE) is important in the modulation of the catabolism of chylomicron and very low density lipoprotein (VLDL) remnants. ApoE has three major genetically determined isoproteins in plasma, designated apoE-2, apoE-3 and apoE-4, with homozygosity for the allele coding for apoE-2 being associated with dysbetalipoproteinemia or type III hyperlipoproteinemia (HLP). We describe a new variant of apoE, apoE-1Harrisburg, which is, in contrast to apoE-2, dominantly associated with type III HLP. Five of twelve members of the affected kindred are heterozygous for the mutant form of apoE, and four of the five have type III HLP, while the fifth member has dysbetalipoproteinemia on diet therapy. Neuraminidase digestion, which removes charged sialic acid residues, did not alter the electrophoretic position of the apoE-1Harrisburg isoprotein, indicating that the altered charge of apoE-1Harrisburg was not due to sialic acid addition to the apolipoprotein. Cysteamine modification, which adds a positively charged group to cysteine, resulted in a shift of apoE-1Harrisburg from the E-1 to the E-2 isoform position, indicating that there is one cysteine in apoE-1Harrisburg as is the case for apoE-3. These results are consistent with apoE-1Harrisburg originating in the allele for apoE-3 with the mutation leading to a negative two-unit charge shift. The definitive identification of a kindred with an apoE variant, apoE-1Harrisburg, dominantly associated with dysbetalipoproteinemia and type III HLP provides a unique opportunity to gain important insights into the structure-function requirements of the E apolipoprotein as well as the mechanisms by which apoE modulates lipoprotein metabolism.

Adolescent↗
PubMed2005

Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer's and Parkinson's diseases.

There are two functional Omega class glutathione transferase (GST) genes in humans. GSTO1 is polymorphic with several coding region alleles, including an A140D substitution, a potential deletion of E155 and an E208K substitution. GSTO2 is also polymorphic with an N142D substitution in the coding region. We investigated the effect of these variations on the enzyme's thioltransferase, dehydroascorbate reductase, monomethylarsonate reductase and dimethylarsonate reductase activities. Variant proteins were expressed in Escherichia coli and purified by Ni-agarose affinity chromatography. GSTO2-2 was insoluble and had to be dissolved and refolded from 8 M urea. The A140D and E208K substitutions in GSTO1-1 did not alter specific activity. The deletion of E155 caused a two- to three-fold increase in the specific activity with each substrate. This deletion also caused a significant decrease in the enzyme's heat stability. The E155 deletion has been linked to abnormal arsenic excretion patterns; however, the available data do not clearly identify the cause of this abnormality. We found that GSTO2-2 has activity with the same substrates as GSTO1-1, and the dehydroascorbate reductase activity of GSTO2-2 is approximately 70-100-fold higher than that of GSTO1-1. The polymorphic N142D substitution had no effect on the specific activity of the enzyme with any substrate. The most notable feature of GSTO2-2 was its very high dehydroascorbate reductase activity, which suggests that GSTO2-2 may significantly protect against oxidative stress by recycling ascorbate. A defect in ascorbate metabolism may provide a common mechanism by which the Omega class GSTs influence the age-at-onset of Alzheimer's and Parkinson's diseases.

Age of Onset↗
PubMed2002

Fatty acid binding protein-2 gene variants and insulin resistance: gene and gene-environment interaction effects.

The intestinal fatty acid binding protein (FABP2) gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty acid (FA) absorption and metabolism and may, therefore, affect insulin sensitivity and glucose metabolism. Numerous studies have assessed FABP2 gene variants and their association with insulin resistance and type 2 diabetes. Some weak evidence indicates that the silent variants and those in the noncoding regions of the gene (codon 118, 3' noncoding region, intron 2 trinucleotide repeat) might be associated with insulin resistance/type 2 diabetes. The most extensively studied variant is the missense Ala54Thr variation, which is common in diverse populations and results in increased FA absorption in vivo. Some evidence indicates that this variant may be associated with insulin sensitivity/type 2 diabetes. However, the large majority of studies assessing the potential association between the Ala54Thr FABP2 variant and insulin resistance/type 2 diabetes did not account for the independent and substantial effects of body composition, habitual physical activity (PA) levels, and diet on insulin resistance. We recently reported that there was an association between Ala54Thr FABP2 genotypes and insulin sensitivity after accounting for the independent effects of body composition and habitual PA levels on insulin sensitivity. Furthermore, others have demonstrated that Ala54Thr FABP2 may associate with insulin sensitivity, but only if individuals are consuming a high-fat diet. These results highlight the importance of including behavioral and environmental factors in the design of studies seeking to assess the impact of genes on physiological and clinical outcome phenotypes.

Amino Acid Substitution↗
PubMed1996

Molecular basis of the altered antigenic expression of RhD in weak D(Du) and RhC/e in RN phenotypes.

The RH blood group locus is composed of two sequence-related genes, RHD and RHCE, encoding the D, Cc, and Ee antigens in common Rh-positive phenotypes. In this report, we have analyzed the molecular basis of Rh antigens expression in weak D (Du) and RN donors, in whom there is a severe reduction of the D and C/e antigens, respectively. Genomic and transcript analysis of three unrelated low-grade weak D (Du) variants indicated that the very low expression of the D antigen is not the result of rearrangement or mutation in the coding sequence of the RHO gone. Accordingly, weak D (Du) erythrocytes should carry a normal RhD polypeptide, which is in agreement with the observation that these variants never produce anti-D antibodies. Comparative polymerase chain reaction analysis showed a lower steady-state level of RhD transcripts in weak D (Du) reticulocytes, as compared with normal RhD-positive controls, thus providing direct evidence that the difference between the D antigen of D-positive and weak D (Du) red blood cells is quantitative only. Conversely, analysis of the molecular genetic basis of the RN phenotype Indicated that the severely decreased expression of the RhC and Rhe antigens in three variants is associated with a qualitative alteration identified as a segmental DNA exchange between the RHCE and RHD genes. These genomic rearrangements, which resulted in hybrid RhCe-D-Ce proteins expressing the low frequency Rh32 but not the high incidence Rh46 antigens, involved either axon 4 alone or both exons 3 and 4. These findings show that an identical phenotypical alteration of Rh antigens (reduced expression) may result either from a quantitative or a qualitative alteration of the RH genes expression.

Alleles↗
PubMed1994

Tissue-specific expression of Na(+)-Ca2+ exchanger isoforms.

The sodium-calcium exchanger (NCE) plays a critical role in diverse processes in many different tissues including heart, nerve, and kidney. Surprisingly, the NCE is encoded by a single gene. We have isolated and sequenced a rat renal NCE clone, denoted F1, that was identical to previous rat NCEs, except for two unique sequences: one in the 5'-untranslated region and the other at a site of alternative splicing in the coding sequence. To explore these regions further, we examined NCE transcripts in several tissues using "rapid amplification of cDNA 5'-ends" and polymerase chain reaction amplification. Three species were identified each with a different 5'-end exon spliced to a common NCE core at nucleotide -34 in the 5'-untranslated region. Based on Northern analysis, each of these species had a unique tissue distribution. Whereas the F1 5'-end variant was abundantly expressed only in kidney, a second variant was expressed mostly in heart, and the third variant was expressed ubiquitously elsewhere. Investigation of the region of alternative splicing in the coding sequence also revealed tissue-specific expression of five major species. These findings indicate that the NCE expression is controlled and regulated under the influence of different promoters in a tissue-specific fashion. Therefore, we propose that the structural complexity of the single NCE gene allows it to respond independently to the unique demands of different environments.

Alternative Splicing↗
PubMed2006

Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition.

BACKGROUND: The observation that germline mutations in the oxidative DNA damage repair gene MUTYH cause colorectal cancer (CRC) provides strong evidence that dysregulation of the base excision repair (BER) pathway influences disease susceptibility. It is conceivable that germline sequence variation in other BER pathway genes such as NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 also contribute to CRC susceptibility. METHODS: To evaluate whether sequence variants of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC susceptibility alleles, we screened the coding sequence and intron-exon boundaries of these genes in 94 familial CRC cases in which involvement of known genes had been excluded. RESULTS: Three novel missense variants were identified NEIL2 C367A, TDG3 A196G and UNG2 C262T in patients, which were not observed in 188 healthy control DNAs. CONCLUSION: We detected novel germline alterations in NEIL2, TDG and UNG patients with CRC. The results suggest a limited role for NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 in development of CRC.

3' Untranslated Regions↗

Refine your search to explore more results.