Molecular Genetics of Down's Syndrome: Overexpression of Transfected Human Cu/Zn-Superoxide Dismutase Gene and the Consequent Physiological Changes

Down's syndrome (DS), first described as "congenital anomalies and mental retardation syndrome" in 1846 by Edward Seguin (Zellweger 1981) and later on in 1866 by John Langdon Down, is still the most common genetic abnormality, occurring once per 1000 live births (Hook 1981). It is characterized by severe mental retardation as well as a wide variety of physiological defects, such as reduced viability, morphogenetic abnormalities, increased incidence of leukemia, high susceptibility to infections, and some signs of premature aging (for review, see Smith and Berg 1976; Burgio et al. 1981; de la Cruz and Gerald 1981). In 1959, J. Lejeune demonstrated that patients with DS have an extra copy of chromosome 21 in their cells, a condition called trisomy 21 (Lejeune et al. 1959). The causative factor for most of the trisomy is an ovarian nondisjunction at meiosis, although nondisjunction of paternal origin occurring at the first or second meiotic...