A genetic basis for anomalous band patterns encountered during DNA STR profiling

Area of Science:

• Forensic Science
• Genetics
• Molecular Biology

Background:

• The Forensic Science Service (FSS) has utilized DNA profiling for the UK National DNA Database and forensic casework since 1995.
• Two multiplex short tandem repeat (STR) profiling systems have been employed.
• Anomalous DNA profiles, including triallelic and aberrant diallelic patterns, have been regularly observed.

Purpose of the Study:

• To systematically examine anomalous DNA profiling patterns.
• To elucidate the underlying genetic causes of triallelic and aberrant diallelic patterns.
• To correlate observed patterns with specific genetic mechanisms.

Main Methods:

• Collection and analysis of DNA profiles exhibiting anomalous banding patterns.
• Classification of triallelic patterns based on allele intensity (Type 1: uneven, Type 2: even).
• Investigation of genetic mechanisms including somatic mutation, chromosomal rearrangement, and primer binding site mutations.

Main Results:

• Type 1 triallelic patterns are attributed to somatic mutation at heterozygous loci, with deduced size differences being multiples of four nucleotides.
• Type 2 triallelic patterns are linked to localized chromosomal rearrangements at heterozygous loci.
• Aberrant diallelic patterns can arise from similar genetic events at homozygous loci or from primer binding site mutations reducing amplification efficiency.

Conclusions:

• Visual inspection of triallelic patterns allows inference of their likely genetic basis.
• Aberrant diallelic patterns have multiple potential genetic causes, making direct inference more challenging.
• Understanding these anomalies improves the interpretation of forensic DNA profiles.