Increasing the reach of forensic genetics with massively parallel sequencing

The field of forensic genetics has made great strides in the analysis of biological evidence related to criminal and civil matters. More so, the discipline has set a standard of performance and quality in the forensic sciences. The advent of massively parallel sequencing will allow the field to expand its capabilities substantially. This review describes the salient features of massively parallel sequencing and how it can impact forensic genetics. The features of this technology offer increased number and types of genetic markers that can be analyzed, higher throughput of samples, and the capability of targeting different organisms, all by one unifying methodology. While there are many applications, three are described where massively parallel sequencing will have immediate impact: molecular autopsy, microbial forensics and differentiation of monozygotic twins. The intent of this review is to expose the forensic science community to the potential enhancements that have or are soon to arrive and demonstrate the continued expansion the field of forensic genetics and its service in the investigation of legal matters.

[1]  B. Ludes,et al.  Case report: on the use of the HID-Ion AmpliSeq™ Ancestry Panel in a real forensic case , 2017, International Journal of Legal Medicine.

[2]  Bruce Budowle,et al.  Evaluation of the Illumina(®) Beta Version ForenSeq™ DNA Signature Prep Kit for use in genetic profiling. , 2016, Forensic science international. Genetics.

[3]  Bruce Budowle,et al.  Blind study evaluation illustrates utility of the Ion PGM™ system for use in human identity DNA typing , 2015, Croatian medical journal.

[4]  Migiwa Asano,et al.  A simple identification method for vaginal secretions using relative quantification of Lactobacillus DNA. , 2014, Forensic science international. Genetics.

[5]  C. Deming,et al.  Topographical and Temporal Diversity of the Human Skin Microbiome , 2009, Science.

[6]  Bruce Budowle,et al.  High sensitivity multiplex short tandem repeat loci analyses with massively parallel sequencing. , 2015, Forensic science international. Genetics.

[7]  Ilkka Ojanperä,et al.  Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood. , 2003, Forensic science international.

[8]  D. Tautz Hypervariability of simple sequences as a general source for polymorphic DNA markers. , 1989, Nucleic acids research.

[9]  P. Collins,et al.  Developmental validation of a single-tube amplification of the 13 CODIS STR loci, D2S1338, D19S433, and amelogenin: the AmpFlSTR Identifiler PCR Amplification Kit. , 2004, Journal of forensic sciences.

[10]  K. Mullis,et al.  Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. , 1986, Cold Spring Harbor symposia on quantitative biology.

[11]  Geeta Shakya,et al.  Population Genetics of Vibrio cholerae from Nepal in 2010: Evidence on the Origin of the Haitian Outbreak , 2011, mBio.

[12]  Bruce Budowle,et al.  Flanking region variation of ForenSeq™ DNA Signature Prep Kit STR and SNP loci in Yavapai Native Americans. , 2017, Forensic science international. Genetics.

[13]  Bruce Budowle,et al.  Building Microbial Forensics as a Response to Bioterrorism , 2003, Science.

[14]  Niels Morling,et al.  Massively parallel pyrosequencing of the mitochondrial genome with the 454 methodology in forensic genetics. , 2014, Forensic science international. Genetics.

[15]  H. Druid,et al.  Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results. , 1999, Forensic science international.

[16]  David P. Mindell,et al.  Molecular evidence of HIV-1 transmission in a criminal case , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Niels Morling,et al.  ISO 17025 validation of a next‐generation sequencing assay for relationship testing , 2016, Electrophoresis.

[18]  Lloyd M. Smith,et al.  Fluorescence detection in automated DNA sequence analysis , 1986, Nature.

[19]  Jens Stoye,et al.  Updating benchtop sequencing performance comparison , 2013, Nature Biotechnology.

[20]  Walther Parson,et al.  Evaluation of next generation mtGenome sequencing using the Ion Torrent Personal Genome Machine (PGM)☆ , 2013, Forensic science international. Genetics.

[21]  Benjamin E. Krenke,et al.  Validation of a 16-locus fluorescent multiplex system. , 2002, Journal of forensic sciences.

[22]  In Seok Yang,et al.  Massively parallel sequencing of 17 commonly used forensic autosomal STRs and amelogenin with small amplicons. , 2016, Forensic science international. Genetics.

[23]  T. Luckey Introduction to intestinal microecology. , 1972, The American journal of clinical nutrition.

[24]  Niels Morling,et al.  High-throughput sequencing of core STR loci for forensic genetic investigations using the Roche Genome Sequencer FLX platform. , 2011, BioTechniques.

[25]  Eric S. Lander,et al.  Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011 , 2012, Proceedings of the National Academy of Sciences.

[26]  A. Gaedigk,et al.  The CYP2D6 Activity Score: Translating Genotype Information into a Qualitative Measure of Phenotype , 2008, Clinical pharmacology and therapeutics.

[27]  D. Tester,et al.  Molecular Autopsy of Sudden Unexplained Death in the Young , 2001, The American journal of forensic medicine and pathology.

[28]  D. Hoyert,et al.  The changing profile of autopsied deaths in the United States, 1972-2007. , 2011, NCHS data brief.

[29]  N. Morling Forensic genetics , 2004, The Lancet.

[30]  Kazuyuki Saito,et al.  A novel method for the identification of saliva by detecting oral streptococci using PCR. , 2009, Forensic science international.

[31]  H. Jensen,et al.  Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy. , 2012, Forensic science international.

[32]  Magnus Ingelman-Sundberg,et al.  Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. , 2004, Trends in pharmacological sciences.

[33]  Human genetic variations in oxidative drug metabolism. , 1986, Xenobiotica; the fate of foreign compounds in biological systems.

[34]  N. Pinto,et al.  Comparative evaluation of alternative batteries of genetic markers to complement autosomal STRs in kinship investigations: autosomal indels vs. X-chromosome STRs , 2012, International Journal of Legal Medicine.

[35]  A. Sajantila,et al.  Expansion of Microbial Forensics , 2016, Journal of Clinical Microbiology.

[36]  D. Savage Microbial ecology of the gastrointestinal tract. , 1977, Annual review of microbiology.

[37]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[38]  Á. Carracedo,et al.  Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood , 2015, Archives of Disease in Childhood.

[39]  A. Jeffreys,et al.  Individual-specific ‘fingerprints’ of human DNA , 1985, Nature.

[40]  James H. Bullard,et al.  The origin of the Haitian cholera outbreak strain. , 2011, The New England journal of medicine.

[41]  Bruce Budowle,et al.  STRait Razor v2s: Advancing sequence-based STR allele reporting and beyond to other marker systems. , 2017, Forensic science international. Genetics.

[42]  J. Mullins,et al.  Molecular Epidemiology of HIV Transmission in a Dental Practice , 1992, Science.

[43]  B. Budowle,et al.  Molecular Diagnostic Applications in Forensic Science , 2010 .

[44]  Douglas R Storts,et al.  Developmental validation of the PowerPlex(®) Fusion 6C System. , 2016, Forensic science international. Genetics.

[45]  A. Sajantila,et al.  Global genetic variation of select opiate metabolism genes in self-reported healthy individuals , 2017, The Pharmacogenomics Journal.

[46]  Magnus Ingelman-Sundberg,et al.  Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[47]  B. Budowle,et al.  Internal validation of the GlobalFiler™ Express PCR Amplification Kit for the direct amplification of reference DNA samples on a high-throughput automated workflow. , 2014, Forensic science international. Genetics.

[48]  P. de Knijff,et al.  Male DNA typing from 25-year-old vaginal swabs using Y chromosomal STR polymorphisms in a retrial request case. , 1999, Journal of forensic sciences.

[49]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[50]  R. Berg,et al.  The indigenous gastrointestinal microflora. , 1996, Trends in microbiology.

[51]  P. Danielson,et al.  Molecular Diagnostic Applications in Forensic Science , 2017 .

[52]  D. Foran,et al.  Next‐Generation Sequencing of the Bacterial 16S rRNA Gene for Forensic Soil Comparison: A Feasibility Study , 2016, Journal of forensic sciences.

[53]  M Ingelman-Sundberg,et al.  Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity , 2005, The Pharmacogenomics Journal.

[54]  Borys Wróbel,et al.  Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source , 2013, BMC Biology.

[55]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Hanlee P. Ji,et al.  Next-generation DNA sequencing , 2008, Nature Biotechnology.

[57]  P. Jannetto,et al.  Pharmacogenomics as molecular autopsy for postmortem forensic toxicology: genotyping cytochrome P450 2D6 for oxycodone cases. , 2002, Journal of analytical toxicology.

[58]  A. M. Tarone,et al.  The potential use of bacterial community succession in forensics as described by high throughput metagenomic sequencing , 2013, International Journal of Legal Medicine.

[59]  James R. Knight,et al.  Genome sequencing in microfabricated high-density picolitre reactors , 2005, Nature.

[60]  R. Knight,et al.  The influence of sex, handedness, and washing on the diversity of hand surface bacteria , 2008, Proceedings of the National Academy of Sciences.

[61]  M. Whirl‐Carrillo,et al.  Prediction of CYP2D6 phenotype from genotype across world populations , 2016, Genetics in Medicine.

[62]  A. Sajantila,et al.  Pharmacogenetics in medico-legal context. , 2010, Forensic science international.

[63]  A. L. Fox The Relationship between Chemical Constitution and Taste. , 1932, Proceedings of the National Academy of Sciences of the United States of America.

[64]  August E. Woerner,et al.  Full-gene haplotypes refine CYP2D6 metabolizer phenotype inferences , 2017, International Journal of Legal Medicine.

[65]  Bruce Budowle,et al.  Forensically relevant SNP classes. , 2008, BioTechniques.

[66]  M. Hiratsuka In vitro assessment of the allelic variants of cytochrome P450. , 2012, Drug metabolism and pharmacokinetics.

[67]  M. Ingelman-Sundberg,et al.  The past, present and future of pharmacoepigenomics. , 2010, Pharmacogenomics.

[68]  G. Machin Some causes of genotypic and phenotypic discordance in monozygotic twin pairs. , 1996, American journal of medical genetics.

[69]  Bruce Budowle,et al.  An evaluation of the PowerSeq™ Auto System: A multiplex short tandem repeat marker kit compatible with massively parallel sequencing. , 2015, Forensic science international. Genetics.

[70]  D. Nebert,et al.  The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis , 2006, Nature Reviews Cancer.

[71]  C. Caskey,et al.  DNA typing and genetic mapping with trimeric and tetrameric tandem repeats. , 1991, American journal of human genetics.

[72]  Bruce Budowle,et al.  Accurate, rapid and high-throughput detection of strain-specific polymorphisms in Bacillus anthracis and Yersinia pestis by next-generation sequencing , 2010, Investigative Genetics.

[73]  W Parson,et al.  Inter-laboratory evaluation of SNP-based forensic identification by massively parallel sequencing using the Ion PGM™. , 2015, Forensic science international. Genetics.

[74]  Jacqueline Weber-Lehmann,et al.  Finding the needle in the haystack: differentiating "identical" twins in paternity testing and forensics by ultra-deep next generation sequencing. , 2014, Forensic science international. Genetics.

[75]  H. Notopuro,et al.  Glucose-6-phosphate dehydrogenase deficiency. , 1972, Paediatrica Indonesiana.

[76]  M. Metzker Sequencing technologies — the next generation , 2010, Nature Reviews Genetics.

[77]  R. Milo,et al.  Revised Estimates for the Number of Human and Bacteria Cells in the Body , 2016, bioRxiv.

[78]  L. Smith Automated DNA sequencing and the analysis of the human genome. , 1987, Genome.

[79]  B. Melegh,et al.  Increased prevalence of functional minor allele variants of drug metabolizing CYP2B6 and CYP2D6 genes in Roma population samples , 2015, Pharmacological reports : PR.

[80]  P M Schneider,et al.  A brief history of the formation of DNA databases in forensic science within Europe. , 2001, Forensic science international.

[81]  W. Parson,et al.  Sequence analysis of the canine mitochondrial DNA control region from shed hair samples in criminal investigations. , 2012, Methods in molecular biology.

[82]  Katherine H. Huang,et al.  A framework for human microbiome research , 2012, Nature.

[83]  C. S. Davidson THE AUTOPSY IN THE AGE OF MOLECULAR BIOLOGY. , 1965, JAMA.

[84]  David H. Warshauer,et al.  Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing. , 2015, Legal medicine.

[85]  Bradd J. Haley,et al.  Genomic diversity of 2010 Haitian cholera outbreak strains , 2012, Proceedings of the National Academy of Sciences.

[86]  Woo Ick Yang,et al.  Body fluid identification by integrated analysis of DNA methylation and body fluid-specific microbial DNA , 2013, International Journal of Legal Medicine.

[87]  P. Jannetto,et al.  Pharmacogenomics as molecular autopsy for forensic toxicology: genotyping cytochrome P450 3A4*1B and 3A5*3 for 25 fentanyl cases. , 2005, Journal of analytical toxicology.

[88]  L. Tsai,et al.  A highly polymorphic STR locus in Cannabis sativa. , 2003, Forensic science international.

[89]  Niels Morling,et al.  Introduction of the Python script STRinNGS for analysis of STR regions in FASTQ or BAM files and expansion of the Danish STR sequence database to 11 STRs. , 2016, Forensic science international. Genetics.

[90]  Jennifer D. Churchill,et al.  Effects of the Ion PGM™ Hi-Q™ sequencing chemistry on sequence data quality , 2016, International Journal of Legal Medicine.

[91]  Wei Duan,et al.  Clinical pharmacogenetics and potential application in personalized medicine. , 2008, Current drug metabolism.

[92]  M. Hayden,et al.  Prediction of Codeine Toxicity in Infants and Their Mothers Using a Novel Combination of Maternal Genetic Markers , 2012, Clinical pharmacology and therapeutics.

[93]  B Budowle,et al.  Extraction, PCR amplification and sequencing of mitochondrial DNA from human hair shafts. , 1995, BioTechniques.

[94]  David H. Warshauer,et al.  Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing. , 2016, Forensic science international. Genetics.

[95]  B. Madea,et al.  Medical malpractice as reflected by the forensic evaluation of 4450 autopsies. , 2009, Forensic science international.

[96]  A. Linacre,et al.  An overview to the investigative approach to species testing in wildlife forensic science , 2011, Investigative Genetics.

[97]  Peter M Vallone,et al.  Sequence variation of 22 autosomal STR loci detected by next generation sequencing. , 2016, Forensic science international. Genetics.

[98]  Bruce Budowle,et al.  High-quality and high-throughput massively parallel sequencing of the human mitochondrial genome using the Illumina MiSeq. , 2014, Forensic science international. Genetics.

[99]  Urs A. Meyer,et al.  Pharmacogenetics – five decades of therapeutic lessons from genetic diversity , 2004, Nature Reviews Genetics.

[100]  H. Swerdlow,et al.  A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers , 2012, BMC Genomics.

[101]  M. Eichelbaum,et al.  Defective N-oxidation of sparteine in man: A new pharmacogenetic defect , 1979, European Journal of Clinical Pharmacology.

[102]  H. Goga Comparison of bacterial DNA profiles of footwear insoles and soles of feet for the forensic discrimination of footwear owners , 2012, International Journal of Legal Medicine.

[103]  A. van Belkum,et al.  Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks , 1997, Clinical microbiology reviews.

[104]  David J. Werrett,et al.  Forensic application of DNA ‘fingerprints’ , 1985, Nature.

[105]  L. Jin,et al.  Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. , 1992, Genomics.

[106]  K. Landsteiner,et al.  Ueber Agglutinationserscheinungen normalen menschlichen Blutes , 1901 .

[107]  Bruce Budowle,et al.  Characterization of genetic sequence variation of 58 STR loci in four major population groups. , 2016, Forensic science international. Genetics.

[108]  Gideon Koren,et al.  Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother , 2006, The Lancet.

[109]  Barry Merriman,et al.  Progress in Ion Torrent semiconductor chip based sequencing , 2012, Electrophoresis.

[110]  Bruce Budowle,et al.  Underlying Data for Sequencing the Mitochondrial Genome with the Massively Parallel Sequencing Platform Ion Torrent™ PGM™ , 2015, BMC Genomics.

[111]  H. Iwase,et al.  Detection of bacterial 16S ribosomal RNA genes for forensic identification of vaginal fluid. , 2012, Legal medicine.

[112]  Dieter Deforce,et al.  My-Forensic-Loci-queries (MyFLq) framework for analysis of forensic STR data generated by massive parallel sequencing. , 2014, Forensic science international. Genetics.

[113]  M. Ingelman-Sundberg Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy , 2001, Journal of internal medicine.

[114]  Titia Sijen,et al.  FDSTools: A software package for analysis of massively parallel sequencing data with the ability to recognise and correct STR stutter and other PCR or sequencing noise. , 2017, Forensic science international. Genetics.

[115]  Mihai Pop,et al.  Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation , 2011, Proceedings of the National Academy of Sciences.

[116]  Niels Morling,et al.  Second-generation sequencing of forensic STRs using the Ion Torrent™ HID STR 10-plex and the Ion PGM™. , 2015, Forensic science international. Genetics.

[117]  Pichet Udomratn,et al.  How Thailand has modified the section on mental disorders in the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD‐10) * , 2009 .

[118]  R. Fleming,et al.  The use of bacteria for the identification of vaginal secretions. , 2010, Forensic science international. Genetics.

[119]  A. Amorim,et al.  Handbook of Forensic Genetics:Biodiversity and Heredity in Civil and Criminal Investigation , 2016 .

[120]  K. Mullis,et al.  Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. , 1985, Science.

[121]  W. Zimmerli,et al.  Infectious complications in drug addicts: seven-year review of 269 hospitalized narcotics abusers in Switzerland. , 1989, Reviews of infectious diseases.

[122]  F. Lowy,et al.  Strains of Staphylococcus aureus obtained from drug-use networks are closely linked. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.