CAG repeat length variation in sperm from a patient with Kennedy's disease.
Using a modified sperm typing protocol, the mutation frequency of the CAG repeat region at the androgen receptor locus has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy (SBMA). Among 258 X chromosome-containing sperm, 19% had a repeat number equal to the donor's somatic DNA (47 repeats), 66% were expansions and 15% were contractions. The average expansion was 2.7 repeats. More than half of the expansions involved one or two repeats; the largest was 11 repeats. 68% of the contractions were also one or two repeats but six (16%) were very large (12-25 repeats). One contraction generated an allele in an intermediate size range (33-39 repeats). Such alleles have not been observed among more than 900 normal and SBMA X-chromosomes that have been examined. Comparison of the SBMA sperm typing results with mutation frequency data on normal alleles supports the hypothesis that trinucleotide repeat expansions may have a different molecular origin than contractions.
Zhang
L
L
Molecular Biology Program, USC, Los Angeles 90089-1340, USA.
Fischbeck
K H
KH
Arnheim
N
N
D000483:Alleles; D004247:DNA / Q000032:analysis; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013094:Spermatozoa / Q000737:chemistry*
D011944:Receptors, Androgen; D004247:DNA