title: Genetics, an alternative way to discover, characterize and understand ion channels.
abstract: 1. The conventional approach to understanding the structure and properties of ion channels has been to use physiological characterization. 2. Purification and molecular cloning of ion channel genes has enabled more detailed structure-function analyses to be undertaken. 3. An alternative approach to the identification of genes of pathophysiological importance has been the use of genetic linkage approaches and positional cloning or positional candidate analysis of ion channel genes. 4. Using genetic approaches, mutations have been described that cause inherited neurological disorders of neurons (e.g. epilepsy, migraine, deafness, ataxia and startle disease), skeletal muscle (myotonia, malignant hyperthermia, periodic paralysis and myasthenia) and cardiac muscle (long QT syndrome and ventricular fibrillation). 5. For each disease, gene structure-function analyses of the mutant alleles have provided further insights into the biology of ion channels. 6. The present brief review examines the methods used in genetic linkage studies and positional cloning of disease genes. Understanding how ion channel gene mutations give rise to dysfunctional channels will be important in defining and treating the episodic and chronic channelopathies.
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. p.schofield@garvan.unsw.edu.au
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D023061:Gene Order; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009222:Myotonia / Q000235:genetics*; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D018009:Receptors, Glycine / Q000737:chemistry / Q000235:genetics
chemical_list: D007473:Ion Channels; D018009:Receptors, Glycine