MOLECULAR CHARACTERIZATION OF THE HUMAN APO(A)-PLASMINOGEN GENE FAMILY CLUSTERED ON THE TELOMERIC REGION OF CHROMOSOME-6 (6Q26-27)

The genes coding for apo(a) and plasminogen belong to a family of rela ted genes sharing several structural sequences like leader, kringle, a nd protease domains. YAC cloning has allowed to understand that all th ese genes are clustered within 400 Kb of genomic DNA on the telomeric region of chromosome 6 (6q26 - 27). We have now characterized the two remaining members of the apo(a) and plasminogen gene cluster. One of t hem was found to contain a leader highly homologous to that of apo(a) and plasminogen, followed by several kringle IV-like units, kringle V and protease domains although no tail sequences could be detected. Thi s apo(a)-like gene was found to be expressed at the RNA level in liver although an in-frame stop codon was detected in one of its kringle un its. The other member of the cluster besides the leader shows a plasmi nogen tail-like domain whose sequences contain a frameshift resulting in a stop codon; another mutation, destroying a consensus splicing sit e, has been found in a large intron separating the exon coding for the leader from the one encoding the tail-like sequences. The structural organisation of this cluster suggests that new arrangements of these f our genes will be a likely finding.