STUDYING HUMAN MUTATIONS BY SPERM TYPING - INSTABILITY OF CAG TRINUCLEOTIDE REPEALS IN THE HUMAN ANDROGEN RECEPTOR GENE

Trinucleotide repeat mutations of normal alleles at the human androgen receptor locus were studied by typing similar to 4,300 sperm. Control experiments established that the mutation events were of germline ori gin. The mutation rate for 20-22 repeat alleles was similar to that sh own by family analysis. Alleles with 28-31 repeats had a 4.4 times gre ater rate of mutation with contractions outnumbering expansions. Preli minary experiments on the trinucleotide repeat associated with myotoni c dystrophy gave similar results although in one donor expansions were six times greater than contractions. Comparison of the sperm data to mutations of disease alleles in SBMA families suggests that expansions may have a different origin than contractions.