GENETIC-LINKAGE STUDIES IN ANTITHROMBIN-DEFICIENT KINDREDS USING A HIGHLY POLYMORPHIC TRINUCLEOTIDE SHORT TANDEM REPEAT (STR) WITHIN THE HUMAN ANTITHROMBIN GENE

PCR amplification and analysis of short tandem repeats (STR) have prov ided a useful tool for genetic linkage studies and for the diagnosis o f genetic disorders. We have recently identified a novel trinucleotide STR, (ATT).(TAA), in the fifth intron of the human antithrombin gene (AT3) located on chromosome 1q23. PCR amplification, cloning, and sequ ence analysis revealed this AT3-STR to be highly polymorphic with repe at units ranging in size from (ATT)(5) to (ATT)(18). Ten distinct alle les were found in 81 unrelated Caucasian individuals (162 alleles) wit h an observed heterozygosity of 81%. Genetic linkage studies using the AT3-STR in two previously described antithrombin (AT)-deficient kindr eds, AT-Hamilton (Ala 382 Thr) and AT-Amiens (Arg 47 Cys), demonstrate , in a given kindred, that a specific AT3-STR polymorphism is strongly associated with a particular AT mutation. Thus, this highly polymorph ic AT3-STR should be very useful in performing linkage studies in AT-d eficient kindreds as well as in investigating other chromosome 1-relat ed genetic disorders. (C) 1994 Wiley-Liss, Inc.