A Strategy for Cloning the Hereditary Hemochromatosis Gene

Selective hybridization of small intestine and liver cDNA libraries was carried out using yeast artificial chromosomes (YACs) surrounding D6S105, the microsatellite that appears to be close to the gene for hereditary hemochromatosis (HFE). Of 14 candidate probes hybridizing with these YACs, only one, designated LD5-1, detected abnormalities in Southern blots of patients with hemochromatosis. Two different abnormalities were detected in 3 of 55 patients with hemochromatosis with the LD5-1 probe, and one of these was detected in one of 44 normal subjects. The gene that hybridizes with this probe is located about 300-400 kb centromeric of D6S105. It is transcribed into mRNA that is about 8.5 kb in length in many tissues, including peripheral blood leukocytes. The available sequence indicates that it codes for a zinc finger protein. We propose that there is a reasonable probability that LD5-1 hybridizes with the gene for hereditary hemochromatosis.