From mapping to manipulating the vertebrate genome

Abstract

Genetic (linkage) mapping can provide compelling evidence of the molecular genetic causes of monogenic diseases. The developing genetic maps of vertebrate genomes now also facilitate the identification of the genes controlling polygenic traits. However, mapping a disease gene and even identifying a causal mutation often represents the start rather than the end of studies of the disorder or trait of interest. Knowledge of the molecular basis of a trait or identification of flanking genetic markers can be used for prenatal or presymptomatic screening in Man and can be exploited through marker assisted selection in agriculture.

For genetic diseases of Man, the development of better animal models, on which to test therapies, becomes feasible once the molecular genetic cause of the disease has been identified. Transgenic mice created using homologous recombination in embryo stem cells can provide such effective models. However, experience with such models suggests that even for monogenic diseases the nature of the remainder of the genome can play a crucial role in determining the resulting phenotype.