The mutational spectrum of human autosomal tetranucleotide microsatellites

We studied by multiplex amplification and single‐run electrophoretic analysis 10 microsatellite loci, composed of nine tetranucleotide‐repeats (D1S1612, D3S2387, D4S2431, D5S2501, D10S1237, D15S657, D16S2622, D18S1270, and IFNAR‐ALU) and one trinucleotide repeat (D2S1353). After elimination of proven null allele events involving D1S1612 and D5S2501 and of all data of D3S2387, in which we suspected but could not prove the occurrence of null alleles, we were left with nine loci, encompassing 24,224 meioses and 23 mutations. Twenty‐two of the mutations (96%) were single‐step events. Moreover, 18 of the mutations were paternal, four were maternal, and one was indeterminate. There was no significant difference between the number of additions and deletions in the mutants. Our findings are compatible with a simple model in which tetranucleotide microsatellites mutate primarily in paternal germinative cells by DNA slippage, such that the vast majority of mutations are equiprobable additions or deletions of a single‐repeat unit. By combining the data from our tetranucleotide loci with literature information of highly and lowly mutable microsatellites, we observed a very highly significant correlation between mutation rate and the geometric mean of the length of the longest perfect repeat region (LRPR), compatible with a power or exponential relationship. The variation of the length of the LRPR explained as much as 80% of the variance of the mutation rate of autosomal tetranucleotide microsatellites. Hum Mutat 21:71–79, 2002. © 2002 Wiley‐Liss, Inc.