Identification and cloning of putative human neuronal voltage-gated calcium channel γ-2 and γ-3 subunits

Neurologic implications

John L. Black, Vanda A Lennon

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objective: To identify human genes encoding neuronal voltage-gated calcium channel γ subunits corresponding to the γ subunit recently described in mice with hereditary epilepsy, confirm their expression in adult brain, and determine whether a γ subunit resides in human chromosomal regions with marker genes linked to convulsions. Material and Methods: Human homologues of a recently described mouse γ subunit were sought by a computerized search of National Center for Biotechnology Information databases. Sequences of interest were mapped electronically to specific chromosomal regions. The proximity of these chromosomal regions to markers linked to convulsive disorders was determined by a MEDLINE search. Predicted γ subunit sequences were amplified by polymerase chain reaction from a human adult brain complementary DNA (cDNA) library and were subcloned, and full- length sequences were determined or confirmed. Secondary structure and transmembrane regions were predicted by using the TMpredict program. Results: Two putative isoforms (human γ-2 and γ-3 calcium channel subunits) were identified, cloned, and sequenced. They mapped to chromosomes 22 and 16, respectively. A marker very close to the γ-3 gene gives maximal lod scores for an autosomal dominant syndrome of familial infantile convulsions and paroxysmal choreoathetosis. Conclusion: Genomic DNA sequence data already existed in GenBank (partial for γ-2 and complete for γ-3) for the two putative neuronal calcium channel γ subunits that we identified. By cloning both of these molecules from a cerebellar cDNA library, we demonstrated for the first time their expression in human brain. The γ-3 gene is adjacent to a marker for a convulsive disorder. The convulsive phenotype of γ channelopathies occurring in mice makes the human γ subunit genes attractive candidate genes for hereditary convulsive disorders.

Original languageEnglish (US)
Pages (from-to)357-361
Number of pages5
JournalMayo Clinic Proceedings
Volume74
Issue number4
StatePublished - 1999

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Calcium Channels
Nervous System
Organism Cloning
Genes
Gene Library
Brain
Complementary DNA
Channelopathies
Lod Score
Chromosomes, Human, Pair 16
Information Centers
Chromosomes, Human, Pair 22
Nucleic Acid Databases
Biotechnology
MEDLINE
Epilepsy
Protein Isoforms
Seizures
Databases
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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abstract = "Objective: To identify human genes encoding neuronal voltage-gated calcium channel γ subunits corresponding to the γ subunit recently described in mice with hereditary epilepsy, confirm their expression in adult brain, and determine whether a γ subunit resides in human chromosomal regions with marker genes linked to convulsions. Material and Methods: Human homologues of a recently described mouse γ subunit were sought by a computerized search of National Center for Biotechnology Information databases. Sequences of interest were mapped electronically to specific chromosomal regions. The proximity of these chromosomal regions to markers linked to convulsive disorders was determined by a MEDLINE search. Predicted γ subunit sequences were amplified by polymerase chain reaction from a human adult brain complementary DNA (cDNA) library and were subcloned, and full- length sequences were determined or confirmed. Secondary structure and transmembrane regions were predicted by using the TMpredict program. Results: Two putative isoforms (human γ-2 and γ-3 calcium channel subunits) were identified, cloned, and sequenced. They mapped to chromosomes 22 and 16, respectively. A marker very close to the γ-3 gene gives maximal lod scores for an autosomal dominant syndrome of familial infantile convulsions and paroxysmal choreoathetosis. Conclusion: Genomic DNA sequence data already existed in GenBank (partial for γ-2 and complete for γ-3) for the two putative neuronal calcium channel γ subunits that we identified. By cloning both of these molecules from a cerebellar cDNA library, we demonstrated for the first time their expression in human brain. The γ-3 gene is adjacent to a marker for a convulsive disorder. The convulsive phenotype of γ channelopathies occurring in mice makes the human γ subunit genes attractive candidate genes for hereditary convulsive disorders.",
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N2 - Objective: To identify human genes encoding neuronal voltage-gated calcium channel γ subunits corresponding to the γ subunit recently described in mice with hereditary epilepsy, confirm their expression in adult brain, and determine whether a γ subunit resides in human chromosomal regions with marker genes linked to convulsions. Material and Methods: Human homologues of a recently described mouse γ subunit were sought by a computerized search of National Center for Biotechnology Information databases. Sequences of interest were mapped electronically to specific chromosomal regions. The proximity of these chromosomal regions to markers linked to convulsive disorders was determined by a MEDLINE search. Predicted γ subunit sequences were amplified by polymerase chain reaction from a human adult brain complementary DNA (cDNA) library and were subcloned, and full- length sequences were determined or confirmed. Secondary structure and transmembrane regions were predicted by using the TMpredict program. Results: Two putative isoforms (human γ-2 and γ-3 calcium channel subunits) were identified, cloned, and sequenced. They mapped to chromosomes 22 and 16, respectively. A marker very close to the γ-3 gene gives maximal lod scores for an autosomal dominant syndrome of familial infantile convulsions and paroxysmal choreoathetosis. Conclusion: Genomic DNA sequence data already existed in GenBank (partial for γ-2 and complete for γ-3) for the two putative neuronal calcium channel γ subunits that we identified. By cloning both of these molecules from a cerebellar cDNA library, we demonstrated for the first time their expression in human brain. The γ-3 gene is adjacent to a marker for a convulsive disorder. The convulsive phenotype of γ channelopathies occurring in mice makes the human γ subunit genes attractive candidate genes for hereditary convulsive disorders.

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