Rick W. Staub and Michael G. Carrico
Identigene, Inc., Houston, TX
In a paternity case performed in our laboratory, the alleged father did not possess the child's obligate paternal allele for one STR locus, HUMHPRTB(AGAT)n, but he did match the child's obligate paternal allele at the nine other STR loci in our standard battery of tests. Results of this type can be interpreted in two manners; either the alleged father is closely related to the true biological father, or the alleged father is the biological father and a mutational event occurred in his germ line, producing a new allele in the child. Standard protocol in cases of this type is to extend testing to determine whether another child/alleged father non-match can be found. If a second non-match is found, it is typically concluded that a close relative of the alleged father is the biological father. If extended testing reveals no other non-matches, a mutational event is inferred and an assessment of paternity is typically made for the alleged father with the additional provision that a close relative of the alleged father may be the biological father.
In this particular case, extended testing (four more STR loci, D1S80, and three RFLP loci) produced no more child/alleged father mismatches. The inclusionary systems produce a residual paternity index close to twelve million to one. Additionally, questioning of the parties involved in the case indicated that there was no possibility of sexual intercourse between the mother and any close relative of the alleged father. Thus, the HPRTB non-match between the child (obligate paternal allele is a 14 repeat allele) and the alleged father (possesses a 15 repeat allele) must be due to a mutational event occurring in the alleged father's germ line.
Therefore, we isolated and sequenced these two alleles to determine what sequence changes were involved. The sequence data reveal that the child's obligate paternal allele possesses one less AGAT repeat than does the father's allele. All flanking sequences in the child and father are identical to the GenBank sequence for this region. Since HPRTB is an X-linked locus and the alleged mutational event occurred in the father, it appears that the molecular mechanism responsible for the mutational event is either unequal sister chromatid exchange or replicational slippage by DNA polymerase in the STR region. This case provides a molecular verification of the type of evolutionary change assumed to be responsible for the polymorphic nature of STR regions.
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