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Proceedings of the Australian Physiological and Pharmacological Society Symposium: Ion Channels GENETICS, AN ALTERNATIVE WAY TO DISCOVER, CHARACTERIZE AND UNDERSTAND ION CHANNELS
Author(s) -
Schofield Peter R
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03409.x
Subject(s) - positional cloning , periodic paralysis , channelopathy , myotonia , ion channel , genetics , ataxia , biology , candidate gene , familial hemiplegic migraine , neuroscience , bioinformatics , gene , medicine , mutant , paralysis , migraine , myotonic dystrophy , psychiatry , receptor , aura , migraine with aura
SUMMARY 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.