ACTIVATION OF THE GAMMA-E-CRYSTALLIN PSEUDOGENE IN THE HUMAN HEREDITARY COPPOCK-LIKE CATARACT

The locus for the hereditary human Coppock-like cataract (CCL) is clos ely (inked to a particular combination of polymorphic Taql sites withi n the human gamma-crystallin gene cluster. Mapping of these sites show s that they define a 15 kb region encompassing the gamma D and psi gam ma E gene. The gamma D and the psi gamma E gene were cloned from the C CL chromosome and characterized. The gamma D gene was functionally equ ivalent to its allele cloned from a wild-type chromosome. The CCL psi gamma E gene contains a cluster of sequence changes within and around its TATA box. Together these cause a tenfold increase in the activity of the psi gamma E promoter, raising the level of expression of this g ene to 30% of that of the gamma D gene. The predicted protein product of the psi gamma E gene is a 6 kD N-terminal gamma-crystallin fragment . Reactivation of the psi gamma E gene and concomitant overexpression of the gamma-crystallin fragment could be the cause of the Coppock-lik e cataract.