Development of a novel microarray data analysis tool without normalization for genotyping degraded forensic DNA

Area of Science:

• Forensic Science
• Genetics
• Bioinformatics

Background:

• Investigative Genetic Genealogy (IGG) is a powerful tool for criminal investigations, gaining prominence after the Golden State Killer case.
• The limitations and potential risks of IGG, particularly with degraded DNA samples, require thorough evaluation.
• Microarray-based SNP genotyping platforms are commonly used but can be susceptible to issues with low-quality DNA.

Purpose of the Study:

• To evaluate the performance of microarray-based SNP genotyping with degraded DNA.
• To identify potential problems in genotype determination from degraded DNA using Affymetrix SNP Array 6.0.
• To develop and validate a novel analysis method to improve genotyping accuracy for IGG.

Main Methods:

• Analysis of degraded DNA samples using the Affymetrix Genome-Wide Human SNP Array 6.0 platform.
• Comparison of conventional genotype determination algorithms with a newly proposed method without normalization (nMAP).
• Evaluation of genotyping accuracy and kinship inference capabilities of the nMAP algorithm.

Main Results:

• Degraded DNA profiles generated false heterozygous SNPs and significantly decreased probe signal intensity on microarray chips.
• Conventional normalization algorithms in genotype determination can lead to erroneous genotype calls from noise signals.
• The nMAP algorithm, despite a low call rate, substantially improved genotyping accuracy and confirmed its utility in kinship inferences.

Conclusions:

• Degraded DNA poses significant challenges for accurate SNP genotype determination on microarray platforms.
• The novel nMAP algorithm effectively addresses issues caused by degraded DNA, enhancing genotyping accuracy for IGG.
• The nMAP algorithm represents a valuable contribution to advancing the reliability and application of investigative genetic genealogy.