Genetic Analysis of Serum Alanine Transaminase Activity in Normal and Hepatitis C Virus-Infected Chimpanzees: An Application of Research-Oriented Genetic Management

The hepatic enzyme alanine transaminase (ALT) is a diagnostic marker for liver damage but has a considerable degree of normal variation. We used complex segregation analysis to determine whether evidence exists for major genic determination of normal ALT values in an important animal model, the chimpanzee (Pan troglodytes). Normal ALT values were available for 212 chimpanzees. Available genealogical data allowed assignment of 165 animals to a total of 19 pedigrees; 47 animals were treated as independents. A major gene explaining 60% of the phenotypic variance in normal alanine transaminase (ALT) activity was detected by complex segregation analysis. The allele for high ALT activity had a frequency of 0.20. Polygenes accounted for an additional 20% of the variation. The observation that 80% of the total phenotypic variance is attributable to genetic factors has important implications for studies that use ALT activity in assessments. Genetic analysis of change in ALT activity after inoculation with hepatitis C virus (HCV) in a subset of animals indicated that approximately 30% of the variation in response may also be attributable to genetic factors and that the estimated major locus genotypes differ in their responses. This suggests that genetic components can exert substantial influences on experimental parameters in hepatitis research.