LINKAGE DISEQUILIBRIUM RELATIONSHIPS AMONG 4 POLYMORPHISMS WITHIN THEHUMAN FIBRINOGEN GENE-CLUSTER

The extent of linkage equilibrium was estimated among four recently ch aracterized human fibrinogen restriction fragment length polymorphisms (RFLPs) using a randomly selected group of 110 individuals from Calif ornia, Two coding region RFLPs, RsaI and MnlI (FGA codon 312 and FGB c odon 448, respectively), and two RFLPs located in the 5' flanking regi on of the FGB gene, AluI (HindIII) and HaeIII, were analyzed. Maximum likelihood estimates based on genotypic data indicated that the RsaI p olymorphism in the FGA gene was at apparent linkage equilibrium with t he MnlI, AluI, and HaeIII sites in the FGB gene, but strong linkage di sequilibrium was noted for the MnlI-AluI, MnlI-HaeIII, and AluI-HaeIII RFLP pairs within the latter gene. The discrepancy in disequilibrium relationships among these closely linked RFLPs may indicate a region o f increased recombination between the FGA and FGB RFLP loci. The FGA R saI polymorphism, when used in conjunction with any of the FGB sites e xamined, will provide more detailed linkage or association data than a nalyses that would utilize only FGB sites. Effective use of polymorphi sms within the fibrinogen locus will aid analysis of the relationships between fibrinogen genotype, plasma fibrinogen levels, and risk of ca rdiovascular disease.