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M E Curran

Publications and source records attributed to M E Curran.

24 records · Page 2Linked to original sources
PubMed1995

Molecular characterization and refined genomic localization of three human potassium ion channel genes.

Potassium ion (K+) channels are essential for a variety of cellular functions in both excitable and non-excitable cells and are likely to be involved in the pathogenesis of some cardiovascular and neurological disorders. To be useful in candidate gene analysis of inherited diseases it is important to identify new K+ channel genes and localize these sequences on the human physical and genetic maps. Using fluorescence in situ hybridization (FISH), we mapped two new K+ channel gene containing cosmids, c2-3a and c9-2a, to chromosomes 1 and 19, respectively. Partial DNA sequencing (c2-3a) and restriction enzyme site analysis (c9-2a) established the uniqueness of each clone. We refined the localization of c2-3a, c9-2a and a previously described K+ channel gene KCNA5, (c7-2), by performing contour length measurements of hybridized metaphase chromosomes and determining the average FLpter% value (fractional length relative to the fixed reference point pter x 100%). When compared to ideograms of banded metaphase chromosomes, these FLpter% values correspond to 12p13.31-->p13.33, 1p13.1-->p21.1 and 19q13.32-->q13.33, respectively. Using FISH, each of these clones has been finely mapped to a different human chromosome indicating a significant dispersion of K+ channel sequences in the human genome.

Amino Acid Sequence↗
PubMed1993

The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis.

To identify genes involved in vascular disease, we investigated patients with supravalvular aortic stenosis (SVAS), an inherited vascular disorder that causes hemodynamically significant narrowing of large elastic arteries. Pulsed-field gel and Southern analyses showed that a translocation near the elastin gene cosegregated with SVAS in one family. DNA sequence analyses demonstrated that the translocation disrupted the elastin gene and localized the breakpoint to exon 28. Taken together with our previous study linking SVAS to the elastin gene in two additional families and existing knowledge of vascular biology, these data suggest that mutations in the elastin gene can cause SVAS.

Amino Acid Sequence↗
PubMed1992

Molecular cloning, characterization, and genomic localization of a human potassium channel gene.

Potassium (K+) channels are critical for a variety of cell functions, including modulation of action potentials, determination of resting membrane potential, and development of memory and learning. In addition to their role in regulating myocyte excitability, cardiac K+ channels control heart rate and coronary vascular tone and are implicated in the development of arrhythmias. We report here the cloning and sequencing of a k+ channel gene, KCNA1, derived from a human cardiac cDNA library and the chromosomal localization of the corresponding genomic clone. Oligonucleotides based on a delayed rectifier K+ channel gene were used in PCR reactions with human genomic DNA to amplify the S4-S6 regions of several different K+ channel genes. These sequences were used to isolate clones from a human cardiac cDNA library. We sequenced one of these clones, HCK1. HCK1 contains putative S2-S6 domains and shares approximately 70% sequence homology with previously isolated Shaker homologues. HCK1 was used to screen human cosmid libraries and a genomic clone was isolated. By sequencing the genomic clones, a putative S1 domain and translation initiation sequences were identified. Genomic mapping using human-rodent somatic cell panels and in situ hybridization with human metaphase chromosomes have localized KCNA1 to the distal short arm of human chromosome 12. This work is an important step in the study of human cardiac K+ channel structure and function and will be of use in the study of human inherited disease.

Amino Acid Sequence↗