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The director of the Birth Defects Center at the University of California at San Francisco addresses the reasons for developing good ways of teaching human genetics. Genetic counseling is discussed within the context of several case histories. (SA)

Genetic manipulations of Mn superoxide dismutase (MnSOD), SOD2 expression have demonstrated that altering the level of MnSOD activity is critical for cellular function and life span in invertebrates. In mammals, Sod2 homozygous knockout mice die shortly after birth, and alterations of MnSOD levels are correlated with changes in oxidative damage and in the generation of mitochondrial reactive oxygen species. In this study, we directly tested the effects of overexpressing MnSOD in young (4–6 months) and old (26–28 months) mice on mitochondrial function, levels of oxidative damage or stress, life span, and end-of-life pathology. Our data show that an approximately twofold overexpression of MnSOD throughout life in mice resulted in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production. However, this change in MnSOD expression did not alter either life span or age-related pathology. [ABSTRACT FROM PUBLISHER]

Human paternal uniparental disomy for chromosome 14 (upd(14)pat) presents with skeletal abnormalities, joint contractures, dysmorphic facial features and developmental delay/mental retardation. Distal human chromosome 14 (HSA14) is homologous to distal mouse chromosome 12 (MMU12) and both regions have been shown to contain imprinted genes. In humans, consistent radiographic findings include a narrow, bell-shaped thorax with caudal bowing of the anterior ribs, cranial bowing of the posterior ribs and flaring of the iliac wings without shortening or dysplasia of the long bones. Mice with upd(12)pat have thin ribs with delayed ossification of the sternum, skull and feet. In both mice and humans, the axial skeleton is predominantly affected. We hypothesize that there is an imprinted gene or genes on HSA14/MMU12 that specifically affects rib/thorax development and the maturation of ossification centers in the sternum, feet and skull with little effect on long bone development. [ABSTRACT FROM AUTHOR]

Discusses a study which showed that a genetic model of Down syndrome increased immunoreactivity for makers of endosome fusion and endosome recycling. Abnormalities that are prominent in neurons of the basal forebrain; Factor considered the early known pathology in sporadic Alzheimer's disease; Role essential for App gene triplication.

Identifies the genes responsible for the occurrence of Werner syndrome (WS). Helicase of the recQ subclass; Mechanisms by which helicases might produce variable phenotypes; Relationship between WS and premature aging; Isolation and identification of the putative DNA helicase subclass; Characteristics of the helicase disorders; Pathogenesis of WS.