PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Variants”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 91 records · Page 5Linked to original sources
PubMed1993

Fractionation of the genetic variants of human alpha 1-acid glycoprotein in the native form by chromatography on an immobilized copper(II) affinity adsorbent. Heterogeneity of the separate variants by isoelectrofocusing and by concanavalin A affinity chromatography.

Fractionation of the three main genetic variants (F1, S and A) of human alpha 1-acid glycoprotein (AAG), in their native (sialylated) form, by chromatography on immobilized copper(II) affinity adsorbent was investigated. This chromatographic method had been previously developed to fractionate the desialylated protein variants. For that purpose, the three main AAG phenotypes samples (F1S/A, F1/A and S/A), which had been previously isolated from individual human plasma samples, and an AAG sample from commercial source (a mixture of the phenotypes) were used in the native form. Affinity chromatography of these different samples on an iminodiacetate Sepharose-copper(II) gel at pH 7 resolved two protein peaks, irrespective of the origin of the native AAG sample used. The unbound peak 1 was found to consist of the F1, the S or both variants, depending on the phenotype of the AAG sample used in the chromatography. The bound peak 2 was found to consist of the A variant in a pure form. The fractionation results obtained with native AAG were found to be the same as those originally yielded by the desialylated protein. However, comparison of the interactions of native and desialylated AAG with immobilized copper(II) ions, using an affinity chromatographic method and a non-chromatographic equilibrium binding technique, respectively, showed that desialylation increased the non-specific interactions of the protein with immobilized copper(II) ions. The AAG variants were not fractionated when affinity chromatography was performed using immobilized zinc, nickel or cobalt(II) ions, instead of copper. After purification of each variant in the sialylated form (F1, S and A), their respective heterogeneity was studied by analytical isoelectrofocusing with carrier ampholytes in the pH range 2.5-4.5. In addition, the lectin-binding behaviour of the separate sialylated AAG variants was investigated by affinity chromatography on immobilized concanavalin A.

Adsorption↗
PubMed2000

Separation of hemoglobin variants with similar charge by capillary isoelectric focusing: value of isoelectric point for identification of common and uncommon hemoglobin variants.

Clinical assays for the primary evaluation of congenital hemoglobin (Hb) disorders must detect and identify a variety of Hb variants. We analyzed hemolysates containing Hb variants with similar charge to evaluate the diagnostic sensitivity and specificity of automated capillary isoelectric focusing (CIEF). Peak separation was observed for each variant in samples containing Hb S, D, and G. The calculated isoelectric points (pI) of these variants were significantly different such that each could be identified in a single run with pI as the sole criterion of identification. The pI of Hb C was significantly different from that of Hb E, C-Harlem, and O-Arab. Hb E, C-Harlem, and O-Arab had similar pI and were not readily differentiated. Hb Koln, M-Saskatoon, Aida, and S/Aida hybrid were readily separated from common Hb variants and detected by CIEF. We conclude that CIEF exhibits both diagnostic sensitivity and specificity, and that pI is an objective and specific criterion of Hb variant identification.

Child↗
PubMed1993

Linkage disequilibrium between TAP2 variants and HLA class II alleles; no primary association between TAP2 variants and insulin-dependent diabetes mellitus.

The TAP1 and TAP2 genes, located in the HLA class II region, encode subunits of a peptide transporter. Both genes display limited genetic variability; four different nucleotide substitutions have been found in the TAP2 gene. Here studies on linkage disequilibrium between TAP2 variants and HLA class II alleles are reported, in an attempt to evaluate whether TAP2 variants are associated with insulin-dependent diabetes mellitus (IDDM). As reported previously, a significant decrease of homozygosity for TAP2 alleles encoding alanine at residue 665 (665 Ala) and glutamine at 687 (687 Gln) paralleled by an increase in homozygosity for TAP2 alleles encoding threonine at residue 665 (665 Thr) and a stop codon at 687 (687 Stop), was found in both Finnish and Norwegian IDDM patients compared to random controls. However, a strong linkage disequilibrium between these TAP2 polymorphisms and given HLA-DR and -DQ genes was observed among healthy controls. The frequent 665 Thr and 687 Stop variants were in linkage disequilibrium both with the DR4-DQ8 and the DR3-DQ2 haplotypes, haplotypes which are strongly associated with IDDM. In contrast, the DR1-DQ5 and DR13-DQ6 (e.g. DQB1*0603) haplotypes, which are decreased among IDDM patients, were associated with the 665 Ala and 687 Gln variants. Thus, when DR- and DQ-matched patients and controls were compared, associations of the investigated TAP2 variants and IDDM were no longer detectable. These data, therefore, indicate that the associations previously found between certain TAP2 variants and IDDM are secondary to a primary association between this disease and particular DQ alpha beta heterodimers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

A strongly immunoreactive virion protein of human herpesvirus 6 variant B strain Z29: identification and characterization of the gene and mapping of a variant-specific monoclonal antibody reactive epitope.

We previously identified a 101-kDa apparent molecular mass polypeptide (101K) as the major immunoreactive virion protein of human herpesvirus 6 variant B strain Z29 [HHV-6B(Z29)] and found that the human immune response to this protein is HHV-6-specific (Yamamoto, M., Black, J. B., Stewart, J. A., Lopez, C., and Pellett, P. E., 1990, J. Clin. Microbiol. 28, 1957-1962). We report here the identification and characterization of the gene encoding 101K. We found 81% amino acid identity between an HHV-6B(Z29) open reading frame (ORF) and its homolog in HHV-6A strain U1102 [HHV-6A(U1102)]. The product of this gene was identified as 101K on the basis of both the reactivity of a 101K-specific monoclonal antibody (MAb C3108-103) with a bacterially expressed portion of the gene and the reactivity of polyclonal rabbit antibodies raised against the bacterially expressed protein with 101K expressed by HHV-6B(Z29)-infected cells. MAb C3108-103 reacted with eight of eight variant B isolates and none of six variant A isolates, indicating that it is a variant-specific MAb. The MAb reactivity was mapped to an eight-amino-acid segment of 101K. HHV-6A(U1102) differs from HHV-6B(Z29) by two amino acids in this region; substitution mapping with synthetic oligopeptides mapped the variant B specificity to Asp723, this explaining the failure of the MAb to react with variant A proteins. A set of transcripts appropriately sized for expression of 101K was identified and precisely mapped. The transcripts originated down-stream from either of two TATA boxes located 139 bp apart in the region 5' to the 101K ORF, with one 5'-species being much more abundant. Two independent polyadenylation sites were identified; the canonical polyadenylation signal located 3' to the 101K ORF was used much more frequently than was the atypical polyadenylation signal located within the 101K ORF. These results suggest a complex regulatory mechanism for this gene.

Amino Acid Sequence↗
PubMed1985

Electrophoretic variants of blood proteins in Japanese. IV. Prevalence and enzymologic characteristics of glucose-6-phosphate dehydrogenase variants in Hiroshima and Nagasaki.

Electrophoretic screening of glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PD) was conducted one sample of 9,260 children born to the atomic bomb survivors in Hiroshima (Honshu) and Nagasaki (Kyushu). The prevalence of electrophoretic variants was 0.11% in males and 0.42% in females in Hiroshima, and 0.16% in males and 0.31% in females in Nagasaki. Enzymologic characteristics of 10 variants obtained from three males and seven hemizygous fathers of heterozygous females were examined. As a result, three new types of G6PD variants were identified among five variants detected in Hiroshima, and three new types among five variants in Nagasaki. All the variants except one belonged to Class 3, as defined by Yoshida et al. (1971).

Adolescent↗
PubMed1977

LBA technique in the detection of chromosome variants. I. Chromosomes with known sites of Q variants.

A method is described (LBA method) which used DNA replication pattern in the detection of chromosome variants in man. In Part I, results on chromosomes with known sites of Q-variants, i.e., 5 pairs of acrocentrics, as well as 3 and 4, were presented. Fourty-one variants were detected in a total of 40 acrocentrics. Twenty-eight of them were detected only by the LBA technique; 11 of them being in short arms and 17 of them in centromeres. Seven variants, including 4 of those in satellites, were detected only in QFQ-stained metaphases. Six short-arm variants were observed by both methods. It appears that a sequential QFQ-LBA technique is very useful in the detection of variants in D- or G-group chromosomes.

Centromere↗
PubMed1999

Variants in the sulphonylurea receptor gene: association of the exon 16-3t variant with Type II diabetes mellitus in Dutch Caucasians.

AIMS/HYPOTHESIS: We have analysed to what extent two previously reported single nucleotide polymorphisms in the sulphonylurea receptor gene (SUR1) are associated with Type II (non-insulin-dependent) diabetes mellitus in The Netherlands. Furthermore, we estimated haplotype frequencies in control and diabetic populations, including data extracted from three other studies. METHODS: Subjects with Type II diabetes (n = 388) and normoglycaemic subjects (n = 336) were randomly selected from two population-based studies, the Hoorn and Rotterdam studies. DNA was typed for variants in exon 16 (-3c-->t variant in the splice acceptor site) and exon 18 (Thr759Thr, ACC-->ACT). RESULTS: The genotype frequencies in both populations were similar. We observed an association of the exon 16-3t variant with Type II diabetes (allele frequencies 0.41 % vs 0.48 % in NGT and Type II diabetes, respectively, p = 0.01). There was no association between Type II diabetes and the variant in exon 18 or the combination of both variants (p > 0.5). A strong linkage disequilibrium between the exon 16 and exon 18 variants was observed in the diabetic groups but not, or less pronounced, in the control groups from the different studies. Haplotype estimation shows that several different risk haplotypes exist in different Caucasian populations. CONCLUSION/INTERPRETATION: The exon 16-3t allele of the SUR1 gene is associated with Type II diabetes in the Netherlands. Based on estimated haplotype frequencies in different Caucasian populations we conclude that multiple haplotypes on the SUR1 gene seem to confer a risk for developing Type II diabetes in Caucasians.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) variants in the south of Thailand and identification of a novel variant (G6PD Songklanagarind).

Two hundred and twenty-five G6PD-deficient subjects in Songklanagarind Hospital in the south of Thailand comprising 210 males and 15 females were studied. Neonatal jaundice was detected in 85% of these patients. Acute hemolysis related to infection was detected in 17.3% of the G6PD-deficient subjects. Drug-induced acute hemolysis was detected in 1.8% and favism was observed in 3.6% of G6PD-deficient patients. The molecular analysis was performed on 134 G6PD-deficient individuals by a combination of PCR-RFLP, multiplex polymerase chain reaction by multiple tandem forward primers and a common reverse primer assay (MPTP) and DNA sequencing to characterize the mutations of the samples with abnormal MPTP bands. We found 10 different missense G6PD mutations and the three most common variants were G6PD Viangchan 871,G-->A (31.3%), G6PD Kaiping 1388,G-->A (20.1%) and G6PD Mahidol 487,G-->A (17.2%) followed by G6PD Canton 1376,G-->T (9.7%), G6PD Union 1360,C-->T (2.2%), G6PD Gaohe 95,A-->G (1.5%), G6PD Quing Yuan 392,G-->T (0.7%), G6PD Mediterranean 563,C-->T (0.7%), G6PD Songklanagarind 196,T-->A (0.7%), silent mutation 1311,C-->T (6.7%), and uncharacterized variant (9%). A novel missense mutation at codon 196, TTC-->ATC in exon 4 of the G6PD gene predicting a single amino acid substitution, Phe66Ile was identified and we designated this novel class II variant as G6PD Songklanagarind. The G6PD variants among the Thais in the southern part are heterogeneous and G6PD Viangchan, Kaiping, Mahidol, and Canton variants account for about 78% of the cases. Our findings provide some evidence that G6PD Viangchan and Mahidol are common Southeast Asian variants and support the theory of genetic drifts throughout Southeast Asia.

Female↗
PubMed2006

A novel XPC pathogenic variant detected in archival material from a patient diagnosed with Xeroderma Pigmentosum: a case report and review of the genetic variants reported in XPC.

The disease Xeroderma Pigmentosum (XP) is genetically heterogeneous and defined by pathogenic variants (formerly termed mutations) in any of eight different genes. Pathogenic variants in the XPC gene are the most commonly observed in US patients. Moreover, pathogenic variants in just four of the genes, XPA, XPC, XPD/ERCC2 and XPV/POLH account for 91% of all XP cases worldwide. In the current study, we describe the clinical, histopathologic, molecular genetic, and pathophysiological features of a 19-year-old female patient clinically diagnosed with XP as an infant. Analysis of archival material reveals a novel variation of a 13 base pair deletion in XPC exon 14 and a previously reported A>C missense pathogenic variant in the proximal splice site for XPC exon 6. Both variations induce frameshifts most likely leading to a truncated XPC protein product. Quantitative RT-PCR also revealed reduced mRNA levels in the archived specimen. Analysis of the XPA, XPD/ERCC2 and XPV/POLH genes in the current specimen failed to reveal pathologic variants. All previously reported pathogenic variants, polymorphisms and known amino acid changes for the XPC gene are compiled and described in the current nomenclature. Given the relative ease of screening for genetic variation and the potential role for such variation in human disease, a proposal for screening appropriate archival materials for alterations in the four most prevalent XP genes is presented.

Adult↗
PubMed2003

Frequencies of alpha4 A3061G variants and identification of three new variants of the human integrin alpha4-subunit.

Human integrin alpha4beta1 (VLA-4) is thought to play a key role in immune responses. Only two variants of alpha4-subunit (alpha4-tex and alpha4-mas) have been described until now, and the information regarding these variants is scanty. In this study, we measured the frequency of both variants in healthy blood donors (n=252). Surprisingly, the frequency of alpha4-mas (3061G, 0.31) was lower than that of alpha4-tex (3061A, 0.69). In addition, we sequenced and analyzed the mRNA of the entire alpha4-subunit in eight unselected healthy blood donors. These studies revealed three new variants, including a C to A transversion at position 269 in the promoter region of exon 1 (accession no. AJ504733); a G to A transversion at position 2273 in exon 16 (accession no. AJ510246, AJ510247), and a T to C exchange at position 3311 in exon 26 (accession no. AJ510248, AJ510249). None of these variants led to amino acid (AA) substitutions. Interestingly, homozygosity of the new variant 269A was not found.

Adolescent↗
PubMed1996

Two-dimensional RFLP analyses reveal megabase-sized clusters of rRNA gene variants in Arabidopsis thaliana, suggesting local spreading of variants as the mode for gene homogenization during concerted evolution.

Eukaryotic genes encoding the precursor of 18S, 5.8S and 25S ribosomal RNA (rRNA genes or rDNA) are virtually identical within a species, yet they evolve rapidly between species, a phenomenon known as concerted evolution. The mechanisms by which sequence homogenization and fixation of new rRNA gene variants occurs within a genome are not clear. In diploid Arabidopsis thaliana, approximately 1500 rRNA genes are tandemly arrayed at two nucleolus organizer regions, one on chromosome 2 (NOR2), the other on chromosome 4 (NOR4). This paper shows that NOR2 and NOR4 are similar in size, each spanning approximately 3.5-4.0 Mbp. Using two-dimensional mapping techniques involving a combination of pulsed-field and conventional gel electrophoresis, the distributions of four distinct rRNA gene variants at NOR2 and NOR4 have been determined. rRNA genes at NOR4 are homogeneous with respect to a HindIII site occurring once per gene. In contrast, fewer than 10% of the rRNA genes at NOR2 are HindIII-bearing variants. A single intergenic spacer length is found among rRNA genes at NOR2 but three classes of spacer length variants are present at NOR4. The NOR4 variants are not intermingled with one another; instead, they are highly clustered over distances as large as 1.5 Mbp. These data suggest that in the concerted evolution of rRNA genes, homogenization is a consequence of local spreading of new rRNA gene variants.

Arabidopsis↗
PubMed2000

CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity.

OBJECTIVE: To determine the existence of mutant and variant CgammaP3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression. METHODS: A bacterial artificial chromosome that contains the complete CgammaP3A4 gene was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation. RESULTS: To investigate the existence of mutant and variant CgammaP3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human CgammaP3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human CgammaP3A4 gene, designated CgammaP3A4*1B, was found in the three different racial groups. The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The CgammaP3A4*1B allele was not found in Chinese subjects. A second variant allele, designated CgammaP3A4*2, having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 P450 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme but was not significantly different from the wild-type enzyme for testosterone 6beta-hydroxylation. Another rare allele, designated CgammaP3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. CONCLUSIONS: These are the first examples of potential function polymorphisms resulting from missense mutations in the CgammaP3A4 gene. The CgammaP3A4*2 allele was found to encode a P450 with substrate-dependent altered kinetics compared with the wild-type P450.

Alleles↗
PubMed2004

Methionine 129 variant of human prion protein oligomerizes more rapidly than the valine 129 variant: implications for disease susceptibility to Creutzfeldt-Jakob disease.

The human PrP gene (PRNP) has two common alleles that encode either methionine or valine at codon 129. This polymorphism modulates disease susceptibility and phenotype of human transmissible spongiform encyphalopathies, but the molecular mechanism by which these effects are mediated remains unclear. Here, we compared the misfolding pathway that leads to the formation of beta-sheet-rich oligomeric isoforms of the methionine 129 variant of PrP to that of the valine 129 variant. We provide evidence for differences in the folding behavior between the two variants at the early stages of oligomer formation. We show that Met(129) has a higher propensity to form beta-sheet-rich oligomers, whereas Val(129) has a higher tendency to fold into alpha-helical-rich monomers. An equimolar mixture of both variants displayed an intermidate folding behavior. We show that the oligomers of both variants are initially a mixture of alpha- and beta-rich conformers that evolve with time to an increasingly homogeneous beta-rich form. This maturation process, which involves no further change in proteinase K resistance, occurs more rapidly in the Met(129) form than the Val(129) form. Although the involvement of such beta-rich oligomers in prion pathogenesis is speculative, the misfolding behavior could, in part, explain the higher susceptibility of individuals that are methionine homozygote to both sporadic and variant Creutzfeldt-Jakob disease.

Alleles↗