title: Massively parallel sequencing of forensic STRs: Considerations of the DNA commission of the International Society for Forensic Genetics (ISFG) on minimal nomenclature requirements.
abstract: The DNA Commission of the International Society for Forensic Genetics (ISFG) is reviewing factors that need to be considered ahead of the adoption by the forensic community of short tandem repeat (STR) genotyping by massively parallel sequencing (MPS) technologies. MPS produces sequence data that provide a precise description of the repeat allele structure of a STR marker and variants that may reside in the flanking areas of the repeat region. When a STR contains a complex arrangement of repeat motifs, the level of genetic polymorphism revealed by the sequence data can increase substantially. As repeat structures can be complex and include substitutions, insertions, deletions, variable tandem repeat arrangements of multiple nucleotide motifs, and flanking region SNPs, established capillary electrophoresis (CE) allele descriptions must be supplemented by a new system of STR allele nomenclature, which retains backward compatibility with the CE data that currently populate national DNA databases and that will continue to be produced for the coming years. Thus, there is a pressing need to produce a standardized framework for describing complex sequences that enable comparison with currently used repeat allele nomenclature derived from conventional CE systems. It is important to discern three levels of information in hierarchical order (i) the sequence, (ii) the alignment, and (iii) the nomenclature of STR sequence data. We propose a sequence (text) string format the minimal requirement of data storage that laboratories should follow when adopting MPS of STRs. We further discuss the variant annotation and sequence comparison framework necessary to maintain compatibility among established and future data. This system must be easy to use and interpret by the DNA specialist, based on a universally accessible genome assembly, and in place before the uptake of MPS by the general forensic community starts to generate sequence data on a large scale. While the established nomenclature for CE-based STR analysis will remain unchanged in the future, the nomenclature of sequence-based STR genotypes will need to follow updated rules and be generated by expert systems that translate MPS sequences to match CE conventions in order to guarantee compatibility between the different generations of STR data.
authors: Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria; Forensic Science Program, The Pennsylvania State University, University Park, PA, USA. Electronic address: walther.parson@i-med.ac.at.
authors: Walther
authors: W
authors: Parson
authors: Faculty of Life Sciences, King's College, London, UK.
authors: David
authors: D
authors: Ballard
authors: Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Bruce
authors: B
authors: Budowle
authors: National Institute of Standards and Technology, Gaithersburg, MD, USA.
authors: John M
authors: JM
authors: Butler
authors: National Institute of Standards and Technology, Gaithersburg, MD, USA.
authors: Katherine B
authors: KB
authors: Gettings
authors: Norwegian Institute of Public Health, Department of Forensic Biology, Oslo, Norway; Department of Forensic Medicine, University of Oslo, Oslo, Norway.
authors: Peter
authors: P
authors: Gill
authors: DNA Diagnostic Laboratory (LDD), State University of Rio de Janeiro (UERJ), Brazil; IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Portugal; Instituto de Investigação e Inovação em Saúde, University of Porto, Portugal.
authors: Leonor
authors: L
authors: Gusmão
authors: FBI Laboratory, Quantico, VA, USA.
authors: Douglas R
authors: DR
authors: Hares
authors: FBI Laboratory, Quantico, VA, USA.
authors: Jodi A
authors: JA
authors: Irwin
authors: Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors: Jonathan L
authors: JL
authors: King
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Peter de
authors: P
authors: Knijff
authors: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Niels
authors: N
authors: Morling
authors: Department of Sciences, John Jay College for Criminal Justice, New York, NY, USA.
authors: Mechthild
authors: M
authors: Prinz
authors: Institute of Legal Medicine, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Peter M
authors: PM
authors: Schneider
authors: Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors: Christophe Van
authors: CV
authors: Neste
authors: Institute of Legal Medicine, Humboldt University, Berlin, Germany.
authors: Sascha
authors: S
authors: Willuweit
authors: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Galicia, Spain.
authors: Christopher
authors: C
authors: Phillips
mesh_terms: D004247:DNA / Q000235:genetics; D030561:Databases, Nucleic Acid / Q000592:standards; D053803:Forensic Genetics / Q000379:methods* / Q000592:standards*; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D009626:Terminology as Topic
chemical_list: D004247:DNA
keywords: MPS; Massively parallel sequencing; NGS; Next generation sequencing; Nomenclature; STRs; Short tandem repeats