Analysis of minisatellite mutation for performing a highly reliable paternity test without false exclusion

点击翻译按钮获取中文摘要

Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) was devised to map the interspersion pattern of subtle variant repeats along minisatellite tandem arrays. MVR-PCR has revealed enormous diversity of allele structures at, several loci, far more than can be resolved by allele length analysis. We showed that the application of MVR-PCR resulted in higher paternity probabilities than for a set of 12 other classic DNA markers. Hypervariable minisatellites like MS32 and MS31A can however show significant germline mutation rates to new length alleles which can generate false exclusions in paternity cases although paternity cases showing mutant paternal alleles at more than one locus will be rare when several MVR loci are examined. Detailed knowledge of mutation processes coupled with MVR analysis of allele structure can help distinguish mutation from non-paternity. We show how similar mutant alleles are to their progenitors using both real and simulated data, … More and demonstrate how MVR-PCR can be used to identify mutant paternal allele in paternity cases showing apparent exclusions.We analyse minisatellite B6.7 locus in the Japanese population. Allele size distributions showed that Japanese retain extensive allele length variability but have significantly smaller alleles compared to north Europeans. Ninety-two Japanese alleles were further characterised by MVR-PCR. These alleles showed a wide variety of internal MVR structures with most alleles observed only once in the sample. The true heterozygosity is estimated at 99.95%, with well in excess of 2000 different alleles existing in the Japanese population. Dot matrix analysis showed that groups of related alleles sharing structural motifs could be identified within Japanese and in north Europeans, and that these groups are population-specific with no examples of significant similarity between any Japanese and north European alleles. Minisatellite B6.7 therefore shows huge allele variability and fast repeat turnover in Japanese as well as north European populations, and provides novel lineage markers for exploring very recent events in human population history. Less