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R T Taggart

Publications and source records attributed to R T Taggart.

At least 37 records · Page 2Linked to original sources
PubMed1992

Genetic variation of human aspartic proteinases.

The human aspartic proteinases include pepsinogen A, pepsinogen C, cathepsin D, cathepsin E and renin. Comparative analysis of the proteinase genes reveals a high degree of similarity with regard to their respective coding sequences and the location of exon-intron junctions. Despite strong conservation of the regions containing the active site aspartyl groups, genetic polymorphisms have been identified for each of the proteinase genes with the exception of cathepsin D. These genetic polymorphisms are useful for localization of genes on linkage maps as well as determination of gene copy number. The chromosomal location of each aspartyl proteinase has been determined by a variety of gene mapping methods employing recombinant DNA probes including; analysis of somatic cell hybrid mapping panels, in situ hybridization to metaphase chromosome preparations and family linkage analysis with polymorphic markers. Pepsinogen A exhibits the most extensive polymorphism among aspartic proteinases which can be detected by either by protein electrophoresis or by DNA analysis. Southern blot hybridization with respective DNA probes and polymerase chain reaction (PCR) amplification have revealed nucleotide differences located within the coding and noncoding portions of the aspartic proteinase genes. These polymorphisms can be used to investigate potential roles of each proteinase in genetically influenced clinical conditions. The development of additional highly polymorphic markers detected by PCR amplification of divergent nucleotide sequence repeats will greatly assist with documentation of the effect of genetic variation of the aspartic proteinases may have in specific clinical diseases such as ulcer and hypertension.

Amino Acid Sequence↗
PubMed1992

The human loci DNF15S2 and D3S94 have a high degree of sequence similarity to acyl-peptide hydrolase and are located at 3p21.3.

The short arm of chromosome 3 undergoes genetic loss in most small-cell lung cancers and renal cell carcinomas. The most frequently deleted region includes the DNF15S2 locus (mapped to 3p21), suggesting that a putative recessive tumor-suppressor gene might be located nearby. A cosmid clone, cA476, contains the D3S94 locus and two HTF islands and detects a PstI RFLP. We have isolated cDNAs homologous to conserved fragments within cA476; and these cDNAs have 96% sequence similarity to a cDNA derived from the DNF15S2 locus. Sequence information from cDNAs derived from both the rat and pig acyl-peptide hydrolase (E.C.3.4.19.1) gene show that they have a high degree of sequence similarity to cDNAs derived from D3S94 and DNF15S2, suggesting that they are all the same locus. Cosmid cA476 (DNF15S2) has been mapped, by fluorescent in situ hybridization, to chromosome 3p21.3. D3S94 and DNF15S2 are quite distinct from aminoacylase 1 (ACY1), which has been physically linked to D3S2, D3S92, and D3S93, all localized within 3p21.1.

Animals↗
PubMed1991

Human gastric intrinsic factor: characterization of cDNA and genomic clones and localization to human chromosome 11.

A human gastric intrinsic factor (IF) cDNA clone was isolated using a rat cDNA clone as a probe. Comparison of the predicted amino acid sequence revealed 80% identity of human IF with rat IF. These cDNA clones were used to isolate and map two overlapping clones encoding the human IF gene. The first exon of the cloned region (exon 2) contains 30 bp of the 5' untranslated region, the signal peptide, and the first 8 amino acids of the mature protein. Exons 3-10 encode the remainder of the coding and 3' noncoding regions. Southern analysis of genomic DNA indicated the presence of a single human IF gene and also revealed the presence of strong hybridizing sequences in genomic DNA from monkey, rat, mouse, cow, and human, suggesting that the IF gene is well conserved. The IF gene was localized to human chromosome 11 by concurrent cytogenetic and cDNA probe analysis of a panel of human X mouse somatic cell hybrids. Southern analysis of genomic DNA from patients with congenital pernicious anemia (lacking intrinsic factor) revealed normal restriction fragment patterns, suggesting that a sizable gene deletion was not responsible for the deficiency.

Amino Acid Sequence↗
PubMed1990

Human pepsinogen A (PGA): an informative gene complex located at 11q13.

Human pepsinogen (PGA) exhibits extensive polymorphism that can be detected both at the protein and the DNA level. We describe here two restriction fragment length polymorphisms, EcoRI and BglII, which provide for the detection of three of the most common PGA haplotypes (A, B, and C) in the United States population. The relationship of these polymorphisms to each PGA haplotype was determined by analysis of DNA from individuals exhibiting the corresponding protein phenotypes and by analysis of a series of human x mouse somatic cell hybrids containing the individual chromosome 11 homologous from heterozygous individuals exhibiting the AB and AC protein phenotypes. The use of the BglII polymorphism in combination with previously described EcoRI polymorphism provides a very informative marker of 11q13.

Animals↗
PubMed1990

Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids.

A full length cathepsin E (CTSE) cDNA clone was used to assign the corresponding gene to human chromosome region 1q31 by in situ hybridization. Southern blot analysis of DNA from three independent human x rodent somatic cell hybrids containing X;1 translocations confirmed the assignment of the CTSE gene to the distal region of the long arm of chromosome 1.

Blotting, Southern↗
PubMed1990

Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome.

A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the "brown tumors" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in "brown tumors." The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct.

Female↗
PubMed1989

Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases.

The predicted sequence of human gastric cathepsin E (CTSE) was determined by analysis of cDNA clones isolated from a library constructed with poly(A+) RNA from a gastric adenocarcinoma cell line. The CTSE cDNA clones were identified using a set of complementary 18-base oligonucleotide probes specific for a 6-residue sequence surrounding the first active site of all previously characterized human aspartic proteinases. Sequence analysis of CTSE cDNA clones revealed a 1188-base pair open reading frame that exhibited 59% sequence identity with human pepsinogen A. The predicted CTSE amino acid sequence includes a 379-residue proenzyme (Mr = 40,883) and a 17-residue signal peptide. The predicted CTSE amino acid composition was consistent with that of purified material from gastric mucosa and gastric adenocarcinoma cell lines. Additional evidence for the identification of the CTSE cDNA clones was obtained by analysis of poly(A+) RNA isolated from CTSE-producing and -nonproducing gastric adenocarcinoma cell subclones. Three RNA transcripts (3.6, 2.6, and 2.1 kilobases) were identified in poly(A+) RNA isolated from a gastric adenocarcinoma cell line that produced CTSE that were absent from nonproducing subclones. CTSE contains 7 cysteine residues, of which 6 were localized by comparative maximal alignment analysis with pepsinogen A to conserved residues that form intrachain disulfide bonds. The seventh cysteine residue of CTSE is located within the activation peptide region of the proenzyme. We suspect that this residue forms an interchain disulfide bond and thereby determines the dimerization of CTSE proenzyme molecules that is observed under native conditions. The CTSE gene was localized to human chromosome 1 by concurrent cytogenetic and cDNA probe analyses of a panel of human x mouse somatic cell hybrids.

Amino Acid Sequence↗
PubMed1989

Human pepsinogen C (progastricsin). Isolation of cDNA clones, localization to chromosome 6, and sequence homology with pepsinogen A.

The entire pepsinogen C (PGC) coding sequence was determined by analysis of a series of five overlapping cDNA clones identified in a library constructed from human gastric mucosa poly(A+) RNA. A partial cDNA clone was initially identified using a 256-fold degenerate oligonucleotide probe for amino acid residues 4-12 of pepsin C, and subsequently 4 additional clones were identified upon rescreening with a probe complementary to the 5' region of the original cDNA clone. Northern analysis of gastric mucosa poly(A+) RNA with a PGC cDNA probe revealed an mRNA 1.5-kilobase species that was indistinguishable from that detected with a human pepsinogen A (PGA) cDNA probe. In contrast, the PGC and PGA cDNA probes detected distinct genomic restriction fragments indicating there was no detectable cross-hybridization under high stringency conditions. The PGC gene was localized to human chromosome 6 by analysis of a panel of human x mouse somatic cell hybrids. The regions containing the active site aspartyl groups of PGC are conserved in relationship to several other aspartic proteinases. We propose that the absence of detectable immunologic cross-reactivity between the two groups of human pepsinogens, A and C, results from divergent evolution of sequences located on the surface of the zymogens in contrast to the strongly conserved active site regions located within the binding cleft of the enzymes that are inaccessible for antigenic recognition.

Amino Acid Sequence↗
PubMed1989

Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter.

A series of six clones containing the entire human pepsinogen C gene (PGC) was identified in a cosmid vector library by using cDNA and oligonucleotide probes. The 10.7-kb PGC gene includes nine exons and exhibits a high degree of sequence identity (60%) with the functionally related pepsinogen A genes. The predicted amino acid sequence was identical with the partial amino-terminal and carboxyl-terminal sequences of purified pepsinogen C. An informative restriction fragment length polymorphism was detected with several restriction enzymes and involved an insertion or deletion of 100 bp of intron sequence located between exons 7 and 8. Evidence that there is only a single PGC gene in humans is presented. The PGC gene and the prolactin gene were regionally localized to 6p21.1-pter by analysis of mouse X human somatic cell hybrids.

Amino Acid Sequence↗