Molecular characterisation 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 familyof related genes sharing several structural sequences like leader,krlngle, and protease domains. YAC cloning has allowed to understandthat all these genes are clustered within 400 Kb of genomicDNA 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 them was found to containa leader highly homologous to that of apo(a) and plasminogen,followed by several kringle IV-like units, kringle V and proteasedomains although no tall sequences could be detected. This apo(a)-likegene was found to be expressed at the RNA level in liver althoughan in-frame stop codon was detected in one of its kringle units.The other member of the cluster besides the leader shows a plasminogentail-like domain whose sequences contain a frameshift resultingin a stop codon; another mutation, destroying a consensus splicingsite, has been found in a large Intron separating the exon codingfor the leader from the one encoding the tail-like sequences.The structural organisation of this cluster suggests that newarrangements of these four genes will be a likely finding.