AJP - Renal Physiology, Vol 255, Issue 6 1047-F1058, Copyright © 1988 by American Physiological Society
Physiological processes revealed through an analysis of inborn errors
J. J. Gargus and M. Mitas
Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322.
To develop the significance of human inborn errors of membrane function in
terms of their potential for the elucidation of physiological processes, an
overview of the genetics of inherited metabolic disorders is first
presented, concisely covering classical Mendelian inheritance and
progressing to molecular applications currently being used in the isolation
of a number of disease-causing genes. Second, approaches to the isolation
of several genes implicated in inherited disorders of membrane function are
discussed. Examples are drawn from studies of the Shaker/IA K+ channel
mutants of Drosophila and human inborn errors in the low-density
lipoprotein receptor and Kidd antigen/urea transporter. These examples
illustrate the techniques of "reverse" genetics, restriction
fragment-length polymorphism analysis, chromosomal walking, and cDNA
library screening with oligonucleotides and antibodies. Finally, the need
to develop a physiological functional analysis of the protein structures
derived from isolated human disease-causing genes is presented as a
necessary direction for future research.
