The tetranucleotide repeat polymorphism D21S1245 demonstrates hypermutability in germline and somatic cells

Six novel polymorphic short sequence repeats were identifiedand localized on the linkage map of human chromosome 21 by genotypingthe CEPH reference pedigrees. One of these markers, the tetrameric(AAAG)_n repeat D21S1245, was found to be hypermutable. In theDNAs from lymphoblastoid cell lines of members of the 40 CEPHfamilies a total of 18 new alleles were detected. These newalleles, sometimes appearing in mosaic forms, arose equallyin paternal and maternal DNAs, and could be equally larger orsmaller than the alleles from which they were derived. The largeralleles of D21S1245 are more prone to be converted to new alleles.None of the new alleles with mosaicism were present in the correspondinggenomic blood DNA, and therefore originated during or afterthe establishment of the lymphoblastoid cell lines; half ofthe new alleles without mosaicism were also found in genomicblood DNA of the appropriate CEPH individuals. The range ofgermline mutation rate observed In the 716 meioses examinedwas 0.56–1.4x10^–2 the range of somatic mutationsobserved in the 405 cell lines examined was 1.96–3.46x10^–2This is one of the most hypermutabie microsatellite repeat polymorphismin the human genome detected to date. D21S1245, is highly polymorphic(heterozygosity of 0.96) and maps between D21S231 and D21S198.