IDENTIFICATION OF REPEAT SEQUENCE HETEROGENEITY AT THE POLYMORPHIC SHORT TANDEM REPEAT LOCUS HUMTHOI[AATG](N) AND REASSIGNMENT OF ALLELES IN POPULATION ANALYSIS BY USING A LOCUS-SPECIFIC ALLELIC LADDER

An allelic ladder containing amplified sequences of seven alleles of t he polymorphic human tyrosine hydroxylase locus, HUMTH01, was construc ted and employed as a standard marker. Sequence analysis of each ladde r component indicates that fragments differ by integral multiples of t he AATG core repeat sequence characteristic of this locus. Individual alleles are designated ''5'' through ''11,'' according to the number o f complete reiterations of the core repeat contained within them. Comp arison of the HUMTH01 allelic ladder with DNA samples amplified at thi s locus revealed core repeat length heterogeneity (i.e., deletions or insertions shorter than one core repeat) within the human population. In particular, a common allele was identified which migrates more quic kly than allele 10, but more slowly than allele 9, on electrophoresis through a denaturing polyacrylamide gel. Sequence analysis of this all ele, designated ''10-1,'' reveals lack of a single adenine normally pr esent in the seventh copy of the AATG. The allelic ladder was used to reevaluate previously published population data. Results of testing fo r Hardy-Weinberg equilibrium and population substructure were not alte red significantly by these modifications.