DIFFUSE INTERSTITIAL PULMONARY FIBROSIS IN A MOTHER AND SON WITH VON RECKLINGHAUSEN'S DISEASE.

Abstract

<h3>Abstract</h3> Single nucleotide polymorphism (SNP) data generated with microarray technologies have been used to solve murder cases via investigative leads obtained from identifying relatives of the unknown perpetrator included in accessible genomic databases, referred to as investigative genetic genealogy (IGG). However, SNP microarrays were developed for relatively high input DNA quantity and quality, while SNP microarray data from compromised DNA typically obtainable from crime scene stains are largely missing. By applying the Illumina Global Screening Array (GSA) to 264 DNA samples with systematically altered quantity and quality, we empirically tested the impact of SNP microarray analysis of deprecated DNA on kinship classification success, as relevant in IGG. Reference data from manufacturer-recommended input DNA quality and quantity were used to estimate genotype accuracy in the compromised DNA samples and for simulating data of different degree relatives. Although stepwise decrease of input DNA amount from 200 nanogram to 6.25 picogram led to decreased SNP call rates and increased genotyping errors, kinship classification success did not decrease down to 250 picogram for siblings and 1^st cousins, 1 nanogram for 2^nd cousins, while at 25 picogram and below kinship classification success was zero. Stepwise decrease of input DNA quality via increased DNA fragmentation resulted in the decrease of genotyping accuracy as well as kinship classification success, which went down to zero at the average DNA fragment size of 150 base pairs. Combining decreased DNA quantity and quality in mock casework and skeletal samples further highlighted possibilities and limitations. Overall, GSA analysis achieved maximal kinship classification success from 800-200 times lower input DNA quantities than manufacturer-recommended, although DNA quality plays a key role too, while compromised DNA produced false negative kinship classifications rather than false positive ones. <h3>Author Summary</h3> Investigative genetic genealogy (IGG), i.e., identifying unknown perpetrators of crime via genomic database-tracing of their relatives by means of microarray-based single nucleotide polymorphism (SNP) data, is a recently emerging field. However, SNP microarrays were developed for much higher DNA quantity and quality than typically available from crime scenes, while SNP microarray data on quality and quantity compromised DNA are largely missing. As first attempt to investigate how SNP microarray analysis of quantity and quality compromised DNA impacts kinship classification success in the context of IGG, we performed systematic SNP microarray analyses on DNA samples below the manufacturer-recommended quantity and quality as well as on mock casework samples and on skeletal remains. In addition to IGG, our results are also relevant for any SNP microarray analysis of compromised DNA, such as for the DNA prediction of appearance and biogeographic ancestry in forensics and anthropology and for other purposes.