DNA-minisatellite mutations: Recent investigations concerning distribution and impact on parentage testing

Abstract

At least 815 meioses were studied in the HinfI polymorphisms of DNA minisatellite loci D1S7, D2S44, D7S21, D7S22, and D12S11 in order to collect data on respective mutation rates. At locus D7S21 (probe MS31) a striking difference between the paternal and maternal mutation rate was observed (1.5% versus 0.2%). This study also describes, how to deal biostatistically with paternal mutations in parentage testing. Possible implications of mutations are illustrated by the description of 2 cases. Case 1 reports an "exclusion" of mother and father with probe MS1. Case 2 describes 2 paternal "exclusions" with probes MS31 and G3. The statistical likelihood for a paternal "exclusion" with 2 of the 5 probes is 0.13%. By omitting probe MS1, this frequency can be reduced to 0.02%. Nevertheless, the second case clearly shows, that informative blood group markers cannot be replaced by DNA polymorphisms.

Recent observations in human DNA-minisatellite mutations

“…This has to be taken into consideration, especially in parentage testing. In previous papers we reported mutation rates at VNTR loci [10,11]. Due to the increased number of observations, we are now able to update and to review earlier data and to describe the expansion of repeats in mutant paternal alleles at 2 loci.…”

“…If in serologically established families one single restriction fragment of a child could not be exactly attributed to either parent by visual comparison in side-by-side runs we declared this a mutation, regardless of whether the respective difference of size measurement was within the range of our standard deviation of 1.8% or not [9,11]. The standard deviation is only used to calculate the "allele" frequency.…”

“…Various authors have shown that at some loci, paternal and maternal mutations arise with similar frequency, whereas at others, a strong male bias exists [11,19,21,23,29]. This has to be taken into consideration, especially in parentage testing.…”

“…Germline length mutations at human DNA loci have been encountered in human pedigrees [11,17,23,27]. Various authors have shown that at some loci, paternal and maternal mutations arise with similar frequency, whereas at others, a strong male bias exists [11,19,21,23,29].…”

Population genetic diversity in relation to microsatellite heterogeneity

“…Confirmation of the putative father was considered positive if the PI (paternity index) was >1,000 (equivalent to probabilities of 99.9%) even if a low frequency of the new mutation was statistically considered . This calculation included also the approximate mutation rates (Henke et al, 1993).…”