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Biomedical subjects

R G Gregg

Publications and source records attributed to R G Gregg.

13 recordsLinked to original sources
PubMed1992

Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent calcium channels are encoded by a single gene.

Clones of the beta 1-subunit of the voltage-dependent calcium channel (VDCC) from human skeletal muscle and hippocampus cDNA libraries, and from human genomic libraries, were isolated using a human skeletal muscle beta 1 cDNA probe generated by polymerase chain reaction. The skeletal muscle beta 1 cDNA (beta 1M) encodes a protein of 523 amino acids that is 97% identical to the rabbit skeletal muscle beta-subunit. Two different cDNAs, beta 1B1 and beta 1B2, were obtained from the human hippocampus library. The beta 1B1 transcript encodes a protein of 478 amino acids that is identical to the skeletal muscle beta-subunit (beta 1M), except for an internal region of 52 amino acids. The beta 1B2 transcript encodes a protein of 596 amino acids. The beta 1B2 polypeptide is identical to the beta 1B1 polypeptide at amino acids 1-444; however, it has a unique 152 amino acid carboxyl terminus. Like beta 1B1, it differs from beta 1M at the internal 52 amino acids. Analysis of the beta 1 gene structure demonstrates that these three cDNAs represent transcripts encoded by a single beta 1 gene. Transcripts from the beta 1 gene were detected in RNA from skeletal muscle, heart, spleen, and brain, but not in RNA from liver, stomach, or kidney.

Amino Acid Sequence↗
PubMed1992

A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia.

A point mutation in the human gene for the skeletal muscle calcium release channel (ryanodine receptor [RYR1]) correlates with inheritance of malignant hyperthermia in a family of Northern European descent. The substitution of thymine for cytosine at position 1840 of the RYR1 transcript results in a cysteine-for-arginine substitution at position 614 (R614C) of the amino acid sequence. The mutation was absent in 59 normal individuals from the general population, in 61 additional unrelated malignant hyperthermia-susceptible patients, and in 18 patients with malignant hyperthermia associated with other inherited or congenital diseases. Together with reports of an equivalent mutation in six susceptible pig strains and an identical mutation in one other human pedigree, these findings suggest that the cysteine-for-arginine mutation represents a shared calcium release channel pathogenesis between porcine malignant hyperthermia and a subset of mutations responsible for the human malignant hyperthermia syndrome.

Adult↗
PubMed1991

Current issues in neonatal screening for cystic fibrosis and implications of the CF gene discovery.

Many questions remain regarding the efficacy, toxicity, and costs of CF neonatal screening. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. In addition, the ethical issues described herein need to be resolved. This pertains not only to the CF patient but also the heterozygote carrier. These reservations notwithstanding, the discovery of the CF gene should have a favorable impact both directly and indirectly on neonatal screening for the disease. Mutation analysis coupled to IRT testing seems most attractive at this time, at least on a research basis, but primary molecular diagnostic procedures might supervene in the future, particularly if they are financially feasible.

Chromosome Mapping↗
PubMed1991

Waisman syndrome, a human X-linked recessive basal ganglia disorder with mental retardation: localization to Xq27.3-qter.

Linkage of the gene responsible for an X-linked early onset parkinsonism disorder with mental retardation (McKusick 311510) to DNA probes that detect restriction fragment length polymorphisms is described. The disease gene is linked to the F8C gene, and to DNA probes detecting polymorphic loci DXS52, DXS15, DXS134, and DXS374 with maximum lod scores at theta = 0 of 5.08, 5.19, 5.00, 5.03, and 4.46, respectively. Multipoint linkage analysis gives a maximum multipoint lod score of 6.75 at the F8C gene. This places the disease gene in chromosomal region Xq27.3-qter.

Basal Ganglia Diseases↗
PubMed1991

Assignment of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CCHL1A1) to chromosome 12p12-pter.

A human clone corresponding to the gene encoding the alpha 1 subunit of the cardiac dihydropyridine-sensitive calcium channel (CCHL1A1) has been isolated and partially sequenced. Oligonucleotides based on the human sequence were constructed and used in the polymerase chain reaction to amplify specifically this human gene in human-rodent somatic cell hybrids. Using somatic cell hybrids that contained defined regions of human chromosome 12, the human alpha 1 subunit of the cardiac dihydropyridine-sensitive calcium channel has been assigned to the short arm of chromosome 12 in the interval 12p12-pter.

Amino Acid Sequence↗
PubMed1990

Regulatory elements in the introns of the human HPRT gene are necessary for its expression in embryonic stem cells.

We have examined the expression of transfected human hypoxanthine phosphoribosyltransferase minigenes (HPRT) in mouse embryonic stem (ES) cells. cDNA constructs of this gene that have been successfully used in somatic cell lines failed to confer hypoxanthine/aminopterin/thymidine (HAT) resistance in ES cells. In contrast, constructs containing introns 1 and 2 from the HPRT gene produced a high frequency of HAT-resistant colonies. This observation allowed us to identify two sequences in these introns that influence expression of the HPRT gene in ES cells. One element, located in intron 2, is required for effective HPRT expression in these cells; the other element, located in intron 1, acts as an enhancer of HPRT expression. Using this information, we have constructed an HPRT minigene that can be used for either positive or negative selection in ES cell experiments. This dual capability allows the design of "in-out" procedures to create subtle changes in target genes by homologous recombination with the aid of this selectable minigene.

Animals↗