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At least 649 records · Page 36Linked to original sources
PubMed2002

Identification of Ugandan HIV type 1 variants with unique patterns of recombination in pol involving subtypes A and D.

Most HIV-1 infections in Uganda are caused by subtypes A and D. The prevalence of recombination and the sites of specific breakpoints between these subtypes have not been reported. HIV-1 pol sequences encoding protease (amino acids 1-99) and reverse transcriptase (amino acids 1-324) from 102 pregnant Ugandan women were analyzed by the Recombinant Identification Program, SimPlot, and examination of phylogenetically informative sites to identify sites of recombination between sequence segments belonging to different subtypes. Thirteen percent (13 of 102) of the pol sequences contained strong evidence of recombination between subtypes A and D. At least nine different patterns of recombination were observed. Five women infected with a recombinant virus transmitted the recombinant virus perinatally. In this population-based study, intersubtype recombinants were common. The large number of different types of pol recombinants identified suggests that recombination occurs readily in the pol region. Perinatal transmission of the recombinant viruses demonstrates their evolutionary stability.

Databases, Nucleic Acid↗
PubMed2004

Identification and characterization of a novel splice variant of mouse and rat cytochrome b5/cytochrome b5 reductase.

Cytochrome b5/cytochrome b5 reductase (cb5/cb5r) is a cytosolic fusion protein between the hemoprotein cytochrome b5 and the flavoprotein cytochrome b5 reductase. We describe the identification and characterization of a novel splice variant of cb5/cb5r in the mouse and rat and show that expression of the variant is conserved in both species but is not expressed in human tissue. Characterization of the exon structure of cb5/cb5r indicated that the variant was due to the deletion of the whole of exon 12, thus the variant was named cb5/cb5rdelta12. Exon 12 codes for the flavin-adenine dinucleotide binding domain of cb5/cb5r. Expression analysis revealed the transcript of cb5/cb5rdelta12 in mouse and rat testis, brain, and skeletal muscle and also in the male germ line. We postulate that cb5/cb5rdelta12 may function in a dominant negative fashion, limiting the amount of damage caused by the production of reactive oxygen species by cb5/cb5r.

Alternative Splicing↗
PubMed2006

Genomics meets HIV-1.

Genomics is now a core element in the effort to develop a vaccine against HIV-1. Thanks to unprecedented progress in high-throughput genotyping and sequencing, in knowledge about genetic variation in humans, and in evolutionary genomics, it is finally possible to systematically search the genome for common genetic variants that influence the human response to HIV-1. The identification of such variants would help to determine which aspects of the response to the virus are the most promising targets for intervention. However, a key obstacle to progress remains the scarcity of appropriate human cohorts available for genomic research.

AIDS Vaccines↗
PubMed1987

[Nucleotide sequence of the cDNA of kappa casein in cows].

Nucleotide sequence of the cloned DNA complementary to cow kappa-casein mRNA was determined. The complete sequence is composed of 854 bases and includes 60 bases of 5'-noncoding region, 570 bases of the coding region and 209 bases of 3'-noncoding region without poly(A). The cloned sequence codes for kappa-casein, the genetic variant B2. Several restriction sites were defined that permitted the identification of genetic variants and size polymorphism of restriction fragments in the structural region of the gene. Upon the comparative analysis of kappa-casein mRNAs of cow and rat, it was shown that, apart from functionally important regions in the coding sequence, high homology is characteristic of the 5'- and 3'-noncoding regions.

Amino Acid Sequence↗
PubMed1990

Fast atom bombardment mass spectrometric analysis of haemoglobin variants: use of V-8 protease in the identification of Hb M Hyde Park and Hb San Jose.

The characterization of two human haemoglobin variants, Hb M Hyde Park and Hb San José, by fast atom bombardment mass spectrometry is reported. The identification of the site and nature of the amino acid substitution was performed by analysis of the peptide mixture generated by proteolytic digestion of the variant beta-globin chains with V-8 protease. The use of this protease was instrumental in the unambiguous identification of the replaced residues because the tryptic map alone was unable to unequivocally locate the modification. Spectra obtained were easily interpreted and the characterization of Hb M Hyde Park (beta, 92 Hys leads to Tyr) and Hb San José (beta 7 Glu leads to Gly) was accomplished essentially by the same procedure already described for the tryptic map. These results are suggestive of alternative approaches in haemoglobin variants characterization using different proteolytic enzymes when tryptic data alone do not lead to unambiguous results.

Hemoglobin M↗
PubMed2000

Identification of a novel HLA-Cw*07 variant (Cw*0714) in a German Caucasian family.

We report herein the identification of a new HLA-Cw*07 allele in two members of a German Caucasian family. This novel allele, designated as Cw*0714, differs from Cw*07011 and Cw*0706 by two nucleotide changes: one at codon 66 (AAC-->AAG) in the exon 2, leading to an amino acid change from Asn to Lys; and another silent substitution at codon 99 (TAT-->TAC) in the exon 3. The latest substitution (T-->C at the third position of codon 99) was not seen in any of the HLA-Cw*07 alleles reported so far, thus being characteristic to the new HLA-Cw*0714 allele.

Alleles↗
PubMed2006

Identification of a novel HLA-B*44 variant (B*4441) in three unrelated Caucasian individuals.

Here, we report the identification of a new human leukocyte antigen (HLA)-B*44 allele found almost simultaneous in three DNA samples which were part of routine bone marrow donor typing by order of the German registry 'Aktion Knochenmarkspende Bayern'. The samples appeared noticeable in different polymerase chain reactions using sequence-specific primers (PCR-SSP) or sequence-specific oligonucleotides (PCR-SSO). Sequence-based typing revealed a novel allele officially designated as B*4441*. This sequence differs from HLA-B*44020101/4427 by two nucleotide positions at the beginning of exon 3: by position 353 (T to C) and by position 355 (A to C). These differences in sequence result in deviant amino acids at codon 94 (Ile94Thr) and codon 95 (Ile95Leu).

Adult↗
PubMed2000

Rapid detection of DNA sequence variants by conformation-sensitive capillary electrophoresis.

The identification of novel sequence variants, which may be either disease-causing mutations or silent polymorphisms, in large numbers of samples is becoming the rate-limiting step in associating diseases with specific genes. This is particularly true in light of the imminent arrival of the complete reference sequence of the human genome. A number of techniques have been developed to analyze DNA samples for sequence variants rapidly. We describe a new technique, capillary-based conformation-sensitive gel electrophoresis (capillary CSGE) that transfers mutation detection from acrylamide gel to capillary electrophoresis. Capillary CSGE was able to detect 7/7 short insertion/deletions and 16/22 base substitutions in a series of random single-nucleotide polymorphisms and known variants in the lipoprotein lipase and BRCA2 genes. This technique has the potential to screen many megabases of DNA in a single day.

BRCA2 Protein↗
PubMed1997

Combined mass spectrometric methods for the characterization of human hemoglobin variants localized within alpha T9 peptide: identification of Hb Villeurbanne alpha 89 (FG1) His-->Tyr.

Mutation-induced amino acid exchanges occurring on the large T9 peptide of the alpha-chain of human hemoglobin (residues 62-90) are difficult to identify. Despite their high m/z value (around m/z 3000), collision-induced dissociation spectra of liquid secondary ion mass spectrometrically generated protonated alpha T9 peptides were performed successfully. In parallel electrospray mass spectrometry (MS) was used both to measure the molecular mass of the intact proteins and to determine the number of protonatable sites in the alpha T9 peptides. Peptide ladder sequencing using carboxypeptidase digestions and analysis of the truncated peptides by matrix-assisted laser desorption ionization time-of-flight MS confirmed the interpretation. This set of methods allowed the characterization of three hemoglobin variants, with amino acid exchanges located in the alpha T9 part of the sequence. Two of them, Hb Aztec [alpha 76(EF5) Met-->Thr] and Hb M-Iwate [alpha 87(F8) His-->Tyr] were already known. The third [alpha 89(FG1) His-->Tyr] was novel and named Hb Villeurbanne.

Amino Acid Sequence↗
PubMed2006

Aberrant expression of HLA-B*3565Q is associated with a disrupted disulfide bond.

The identification of expression variants is a challenge in HLA diagnostics. We here describe the identification of the novel allele HLA-B*3565Q. The serological HLA class I type, as determined by a lymphocytotoxicity test, was A11,24; B38; Bw4; Cw-; whereas PCR-sequence-specific primers resulted in A*11,*24, B*35,*38; Cw*12, thus suggesting the presence of a nonexpressed B*35 allele. To clarify the lack of serological HLA-B35 reactivity, exons 2 and 3 were sequenced following haplotype-specific amplification. At position 564 from the beginning of the coding region (exon 3), a transversion (C-->G) was observed, which, at the amino acid level, results in a substitution from cysteine to tryptophane at position 164 of the mature polypeptide. Because this position is essential for the formation of a disulfide bond linking the cysteine residues at positions 101 and 164, which is strongly conserved in functional class I molecules of vertebrates, the disruption of this bond is very likely to be the reason for the lack of serological detectability. We later found the same novel allele in a second unrelated individual, of whom we were able to establish a lymphoblastoid cell line (B-LCL). Serological testing of this B-LCL indicated a very low aberrant expression of HLA-B*3565Q, which cannot be expected to be detected by standard serology techniques.

Alleles↗
PubMed2002

Molecular characterization of Hb D-Ibadan [beta87(F3)Thr-->Lys] in combination with Hb S [beta6(A3)Glu-->Val] and with beta+-Thalassemia: report of two cases.

Hb D-Ibadan [beta87(F3)Thr-->Lys] is a common variant in the Nigerian population, which has been reported in association with Hb S [beta6(A3)Glu-->Val] and with beta-thalassemia. Unlike the Hb S/Hb D-Los Angeles [beta121(GH4)Glu-->Gln] combination, compound heterozygosity for Hb D-Ibadan and Hb S does not result in a sickling disorder. We report the first case of a combination of Hb D-Ibadan with beta+-thalassemia, and the first observation of Hb S/Hb D-Ibadan in the African-American population. In both cases, the characterization of Hb D-Ibadan was achieved by sequencing of the genomic DNA. Although protein based methods such as isoelec-trofocusing and high performance liquid chromatography may suggest that the "D-like" variant is different from Hb D-Los Angeles, the definitive identification of the variant by structural analysis or molecular genetic methods should be undertaken, particularly in newborn screening programs when the variant is found in combination with Hb S.

Adult↗
PubMed2004

A comparative method for identification of gene structures and alternatively spliced variants.

MOTIVATION: Alternative splicing (AS) serves as a mechanism to create diversity among functional proteins. Increasing evidence indicates that a large portion of genes have AS forms. Hence AS variants should be considered while analyzing gene structures. RESULTS: A new cross-species gene identification and AS analysis system, PSEP, has been developed. The system is based on expressed sequence tag (EST)-to-genome and genome-to-genome comparisons and is implemented in two steps: sequence alignment and a series of post-alignment processes, including progressive signal extraction and patching. For gene identification, these post-alignment processes serve as noise filters and enable PSEP to eliminate approximately 88% of potential overprediction. The overall accuracy of PSEP is better than or comparable to that of other well-known cross-species gene prediction programs, including the ROSETTA program, TWINSCAN, SGP-1/-2 and SLAM, when tested on three benchmark datasets (the ELN gene region, the HoxA cluster and the ROSETTA set). In addition, 76.2 and 76.0% of multiple-exon genes in the ROSETTA dataset and human chromosome 20, respectively, are found to have AS forms. Approximately 23% of the 210 elementary alternatives identified in the ROSETTA dataset are not conserved between the human and mouse genomes, and none of the 210 transcripts is found in the RefSeq annotation. With its dual functions in cross-species conserved sequence analysis and AS analysis, PSEP is highly suitable for studying the evolution of AS patterns and for finding unidentified gene expression features.

Algorithms↗
PubMed2001

Physiological genomics of antidepressant targets: keeping the periphery in mind.

The plasma membrane transporters that clear extracellular serotonin (5-HT) and norepinephrine (NE), serotonin transporters (SERTs) and NE transporters (NETs), have received considerable attention over the past four decades because of their roles in amine neurotransmitter inactivation. In addition, they interact with many centrally active drugs, including multiple classes of antidepressants such as the serotonin-selective reuptake inhibitors, typified by fluoxetine (Prozac), and the more recently developed norepinephrine-selective transporter antagonists, such as reboxetine. The therapeutic utility of these agents supports biogenic amine theories of affective disorders and raises the question as to whether SERT and NET exhibit a functional genetic variation that could influence risk for behavioral disorders. Although evidence exists that a promoter polymorphism in SERT may influence behavioral states, this contention is not without complexity and its mechanism of action remains poorly understood. The identification of coding variants of NETs and SERTs would offer important opportunities to connect genotype to phenotype. However, given the limited frequency of transporter coding variations evident to date in general population surveys or in psychiatric genetic studies, the identification of informative functional variants of transporters will likely require refined phenotypes. In this regard, NET and SERT play critical roles in cardiovascular and gastrointestinal physiology, respectively. This perspective reviews recent human and mouse studies that suggest how peripheral autonomic phenotypes, linked to genetic disruption of NET and SERT function, can aid in the phenotypic segregation needed for advanced theories of biogenic amine dysfunction and pharmacogenetics.

Antidepressive Agents↗
PubMed1996

Organization and alternate splicing of the murine folylpolyglutamate synthetase gene. Different splice variants in L1210 cells encode mitochondrial or cytosolic forms of the enzyme.

The organization of the murine folylpolyglutamate synthetase (FPGS) gene has been determined by sequence analysis that also revealed an interesting complexity in the case of exon 1. The entire nucleotide sequence of the L1210 FPGS cDNA, the 3'- and 5'-untranslated regions, the mitochondrial leader sequence, and the coding region were found to be distributed on 15 exons with an overall length of 10.358 kilobases. Two splice variants of exon 1 were identified by screening of an L1210 cell cDNA library. Variant I (exons 1a + 1b plus 2-15) incorporates all of the sequence homologous to the recently reported (Taylor, S. M., Freemantle, S. J., and Moran, R. G. (1995) Cancer Res. 55, 6030-6034) human exon 1, including two ATG start codons at positions +1 and +126, and encodes both mitochondrial and cytosolic form of FPGS. The most prevalent variant, Variant II (exons 1b plus 2 to 15), incorporates only a portion (92 nucleotides at the 3' end) of this sequence, incorporates only one ATG start codon at position +126, and encodes only cytosolic FPGS. The existence of this variant is consistent with the identification of an appropriately situated internal donor/acceptor site in what was believed to be exon 1. A third related variant (Variant III) with a novel 5' termini was originally identified by screening of a mouse liver cDNA library. This variant, which occurs at moderately low frequency in the L1210 cell cDNA library, incorporates an alternate to exon 1a (exon 1c) spliced to exon 1b plus exons 2-15 and encodes a different mitochondrial leader peptide than Variant I. The identification of these variants suggests another possible mechanism, i.e. at the level of precursor mRNA splicing, for regulating synthesis of mitochondrial versus cytosolic forms of FPGS in the cell. Exon 1c is positioned in the gene upstream of exon 1a separated by an intron of 56 nucleotides within a region of DNA sequence that like the homologous human sequence is distinctly promoter-like. However, the sequence of this region differs from the human sequence in terms of the number, position, and type of putative regulatory elements, particularly in regard to the number of SP-1 binding sites and the position of multiple transcription start sites as determined by enzymatic primer extension.

Alternative Splicing↗
PubMed2002

Wolfram syndrome: identification of a phenotypic and genotypic variant from Jordan.

Wolfram syndrome is an autosomal recessive disorder with probable locus heterogeneity. Only insulin-dependent diabetes mellitus and progressive optic-nerve atrophy are necessary to make the diagnosis, but associated findings include diabetes insipidus, sensorineural hearing loss, ataxia, peripheral neuropathy, urinary-tract atony, and psychiatric illnesses. We performed clinical and molecular studies on four consanguineous families with 16 affected individuals. We point out a new phenotypic variant with absent diabetes insipidus, presence of peptic ulcer disease and bleeding tendency secondary to a platelet aggregation defect. The same phenotypic variant turned out to be a genotypic variant with linkage to a second Wolfram syndrome locus (WFS2) on chromosome 4q22-24.

Adolescent↗
PubMed2004

Detection and identification of tumor-associated protein variants in human hepatocellular carcinomas.

The proteomic approach is a valuable tool to detect and identify proteins that are associated with cancer. In previous investigations on experimentally induced rat hepatomas, we detected aldose reductase-like protein (ARLP) as a highly significant marker protein. Our present study was intended to look for the presence of similar tumor-associated marker proteins on human hepatocellular carcinomas (HCC). We found several novel tumor-associated protein variants that represent members of the aldo-keto reductase (AKR) superfamily. Human aldose reductase-like protein-1 (hARLP-1) was the most prominent tumor-associated AKR member detected in HCC by 2-dimensional electrophoresis (2-DE) and identified by mass spectrometric fingerprinting. The enzyme was found in 4 distinct forms (hARLP-1, 36/7.4 (kd/pI); hARLP-2, 36/7.2; hARLP-3, 36/6.4; and hARLP-4, 33/7.35). In addition, a human aldose reductase-like protein (hARLP-5, 36/7.6) was identified that differed from hARLP-1 by 1 amino acid (D313N), indicating 2 allelic forms of the human aldose reductase-like gene. A novel antibody directed against common parts of the hARLPs revealed hARLP reactivity in human HCC by immunohistochemistry. Furthermore, aldose reductase (AR) was identified and characterized as a tumor-associated variant. In conclusion, in all investigated human HCCs at least one of the various types of the described tumor-associated proteins of the AKR superfamily was clearly present. Of these HCC samples, 95% were positive for hARLPs as proven by 2-DE analysis and/or by use of the antibody directed against hARLP. Thus, hARLP is a strong candidate for use as an immunohistochemical diagnostic marker of human HCC.

Adult↗
PubMed2003

Identification of a unique BK virus variant in the CNS of a patient with AIDS.

Human polyomavirus BK (BKV; GenBank or EMBL or DDBJ accession no. NC001538) is often reactivated in immunosuppressed patients. Reactivation has been associated primarily with excretion of the virus in the urine, and there have been few reports of renal and/or neurological disease caused by BKV in patients with acquired immunodeficiency syndrome (AIDS). Polymerase chain reaction, Southern blotting, and sequencing were used to detect and identify the noncoding control region (NCCR) of BKV in different tissues in an AIDS patient with meningoencephalitis, retinitis, and nephritis. An undescribed reorganized NCCR variant of the virus, completely different from the variants detected in peripheral blood leukocytes (PBLs) and urine, was identified in the cerebrospinal fluid (CSF) and CNS tissues. These results suggest that rearrangements in the NCCR of the virus have resulted in a BKV variant, which is better adapted to the host cell machinery of the cells in CNS tissue. The rearranged variant (BKV CNS) might have been involved in the initiation and/or development of the pathological lesions observed in the CNS-related tissues of this patient.

AIDS-Related Opportunistic Infections↗