Poly(A/T) tracts are abundant simple sequence repeats (SSRs) within the human genome. They constitute part of the coding sequence of a variety of genes, encoding
polylysine stretches that are important for
protein function. Assessment of
poly(A/T) tract stability is also used to identify microsatellite unstable
colorectal cancers, which are characteristic of tumours defective in DNA mismatch repair. Despite their importance, little is known about the stability of
poly(A/T) SSRs in the human germline. We have determined the stability of a paradigm
poly(A/T) tract, BAT-40, by study of population allele frequencies, mutation frequency in families and mutation frequency in sperm
DNA. We show that the locus is polymorphic, with a level of heterozygosity of 59.7%. Germline mutation was observed in 13 of 187 germline transmissions (7.0%) in 10 families suggesting BAT-40 is unstable in the germline. Further evidence for germline instability at BAT-40 was provided by small pool PCR analysis of matched blood and sperm
DNA templates, revealing a significantly elevated frequency of mutation in the germline (P < 0.001). These findings provide insight into
poly(A/T) tract stability in the germline. They also have relevance to the study of gene expression and to determination of
microsatellite instability in tumours.