Microhaplotypes in forensic genetics.

Microhaplotype loci (microhaps, MHs) are a novel type of molecular marker of less than 300 nucleotides, defined by two or more closely linked SNPs associated in multiple allelic combinations. The value of these markers is enhanced by massively parallel sequencing (MPS), which allows the sequencing of both parental haplotypes at each of the many multiplexed loci. This review describes the features of these multi-SNP markers and documents their value in forensic genetics, focusing on individualization, biogeographic ancestry inference, and mixture deconvolution. Foreseeable applications also include missing person identification, relationship testing, and medical diagnostic applications. The technique is not restricted to humans.

[1]  M. Kayser,et al.  A Practical Guide to the HIrisPlex System: Simultaneous Prediction of Eye and Hair Color from DNA. , 2016, Methods in molecular biology.

[2]  H. Erlich,et al.  Target capture enrichment of nuclear SNP markers for massively parallel sequencing of degraded and mixed samples. , 2018, Forensic science international. Genetics.

[3]  K. Kidd,et al.  Improving ancestry distinctions among Southwest Asian populations. , 2018, Forensic science international. Genetics.

[4]  K. Kidd,et al.  Global variation in CYP2C8–CYP2C9 functional haplotypes , 2009, The Pharmacogenomics Journal.

[5]  K. Kidd,et al.  A global view of the OCA2-HERC2 region and pigmentation , 2011, Human Genetics.

[6]  Eric S. Lander,et al.  A comprehensive genetic map of the mouse genome , 1996, Nature.

[7]  M. Feldman,et al.  Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation , 2008 .

[8]  Zhaohui S. Qin,et al.  A comparison of phasing algorithms for trios and unrelated individuals. , 2006, American journal of human genetics.

[9]  K. Kidd,et al.  Evaluating a subset of ancestry informative SNPs for discriminating among Southwest Asian and circum-Mediterranean populations. , 2016, Forensic science international. Genetics.

[10]  M. Schanfield,et al.  A 50-SNP assay for biogeographic ancestry and phenotype prediction in the U.S. population. , 2014, Forensic science international. Genetics.

[11]  M. Olivier.  A haplotype map of the human genome , 2003, Nature.

[12]  Brian S. Iglehart,et al.  Haplotype counting by next-generation sequencing for ultrasensitive human DNA detection. , 2014, The Journal of molecular diagnostics : JMD.

[13]  Kenneth K Kidd,et al.  Expanding data and resources for forensic use of SNPs in individual identification. , 2012, Forensic science international. Genetics.

[14]  A. Tagliabracci,et al.  A microhaplotypes panel for forensic genetics using massive parallel sequencing , 2017 .

[15]  Perry L. Miller,et al.  ALFRED: an allele frequency database for diverse populations and DNA polymorphisms - an update , 2001, Nucleic Acids Res..

[16]  C R Cantor,et al.  Call for a worldwide survey of human genetic diversity: a vanishing opportunity for the Human Genome Project. , 1991, Genomics.

[17]  Christopher Phillips,et al.  An overview of STRUCTURE: applications, parameter settings, and supporting software , 2013, Front. Genet..

[18]  Bradley P. Coe,et al.  Genome structural variation discovery and genotyping , 2011, Nature Reviews Genetics.

[19]  K. Kidd,et al.  Mongolians in the Genetic Landscape of Central Asia: Exploring the Genetic Relations among Mongolians and Other World Populations , 2015, Human biology.

[20]  D. Altshuler,et al.  A map of human genome variation from population-scale sequencing , 2010, Nature.

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

[22]  D. Reich,et al.  Principal components analysis corrects for stratification in genome-wide association studies , 2006, Nature Genetics.

[23]  N. C. Dracopolia,et al.  A comprehensive genetic linkage map of the human genome. NIH/CEPH Collaborative Mapping Group. , 1992, Science.

[24]  S. Tishkoff,et al.  Global Patterns of Linkage Disequilibrium at the CD4 Locus and Modern Human Origins , 1996, Science.

[25]  Á. Carracedo,et al.  A SNaPshot of next generation sequencing for forensic SNP analysis. , 2015, Forensic science international. Genetics.

[26]  K. Kidd,et al.  Selecting microhaplotypes optimized for different purposes , 2018, Electrophoresis.

[27]  D. Goldstein.  Islands of linkage disequilibrium , 2001, Nature Genetics.

[28]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[29]  S. P. Fodor,et al.  Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21 , 2001, Science.

[30]  N. Qu,et al.  Noninvasive prenatal paternity testing using targeted massively parallel sequencing , 2018, Transfusion.

[31]  Kei-Hoi Cheung,et al.  ALFRED: An allele frequency database for anthropology. , 2002, American journal of physical anthropology.

[32]  N. Morling,et al.  Building a forensic ancestry panel from the ground up: The EUROFORGEN Global AIM-SNP set. , 2014, Forensic science international. Genetics.

[33]  K. Kidd,et al.  Developing a SNP panel for forensic identification of individuals. , 2006, Forensic science international.

[34]  Li Jin,et al.  Diversification of the ADH1B Gene during Expansion of Modern Humans , 2011, Annals of human genetics.

[35]  K. Kidd,et al.  Population-specific variation in haplotype composition and heterozygosity at the POLB locus. , 2009, DNA repair.

[36]  M V Lareu,et al.  Further development of forensic eye color predictive tests. , 2013, Forensic science international. Genetics.

[37]  K. Kidd,et al.  Ancestry inference of 96 population samples using microhaplotypes , 2017, International Journal of Legal Medicine.

[38]  Gabor T. Marth,et al.  An integrated map of structural variation in 2,504 human genomes , 2015, Nature.

[39]  Manfred Kayser,et al.  The HIrisPlex system for simultaneous prediction of hair and eye colour from DNA. , 2013, Forensic science international. Genetics.

[40]  R. Chakraborty,et al.  Haplotype block: a new type of forensic DNA markers , 2009, International Journal of Legal Medicine.

[41]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[42]  Nakanishi Hiroaki,et al.  Approaches for identifying multiple-SNP haplotype blocks for use in human identification. , 2015, Legal medicine.

[43]  Á. Carracedo,et al.  Inferring ancestral origin using a single multiplex assay of ancestry-informative marker SNPs. , 2007, Forensic science international. Genetics.

[44]  K. Kidd,et al.  Current sequencing technology makes microhaplotypes a powerful new type of genetic marker for forensics. , 2014, Forensic science international. Genetics.

[45]  C. E. Pearson,et al.  Table S2: Trans-factors and trinucleotide repeat instability Trans-factor , 2010 .

[46]  E. Anderson,et al.  Microhaplotypes provide increased power from short‐read DNA sequences for relationship inference , 2018, Molecular ecology resources.

[47]  Á. Carracedo,et al.  Tetra-allelic SNPs: Informative forensic markers compiled from public whole-genome sequence data. , 2015, Forensic science international. Genetics.

[48]  Peter Donnelly,et al.  A comparison of bayesian methods for haplotype reconstruction from population genotype data. , 2003, American journal of human genetics.

[49]  K. Kidd,et al.  Microhaplotypes for ancestry prediction , 2017 .

[50]  Michael D. Coble,et al.  Sequence-based analysis of stutter at STR loci: Characterization and utility , 2015 .

[51]  Manfred Kayser,et al.  Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes. , 2015, Forensic science international. Genetics.

[52]  Francisco M De La Vega,et al.  Analyses of a set of 128 ancestry informative single-nucleotide polymorphisms in a global set of 119 population samples , 2011, Investigative Genetics.

[53]  P. Suess,et al.  Comparison of short tandem repeat and variable number tandem repeat genetic markers for quantitative determination of allogeneic bone marrow transplant engraftment , 2002, Bone Marrow Transplantation.

[54]  R. W. Davis,et al.  Distribution of haplotypes from a chromosome 21 region distinguishes multiple prehistoric human migrations. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[55]  S. Gabriel,et al.  The Structure of Haplotype Blocks in the Human Genome , 2002, Science.

[56]  M V Lareu,et al.  Revision of the SNPforID 34-plex forensic ancestry test: Assay enhancements, standard reference sample genotypes and extended population studies. , 2013, Forensic science international. Genetics.

[57]  Á. Carracedo,et al.  A multiplex assay with 52 single nucleotide polymorphisms for human identification , 2006, Electrophoresis.

[58]  Kenneth K Kidd,et al.  Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel , 2013, Investigative Genetics.

[59]  R. Ward,et al.  Informativeness of genetic markers for inference of ancestry. , 2003, American journal of human genetics.

[60]  U. Motro,et al.  Facilitating complex DNA mixture interpretation by sequencing highly polymorphic haplotypes. , 2018, Forensic science international. Genetics.

[61]  Niels Morling,et al.  Next generation sequencing and its applications in forensic genetics. , 2015, Forensic science international. Genetics.

[62]  Titia Sijen,et al.  Tri-allelic SNP markers enable analysis of mixed and degraded DNA samples. , 2009, Forensic science international. Genetics.

[63]  Peter M Schneider,et al.  DNA-based prediction of human externally visible characteristics in forensics: motivations, scientific challenges, and ethical considerations. , 2009, Forensic science international. Genetics.

[64]  L. Kruglyak.  Prospects for whole-genome linkage disequilibrium mapping of common disease genes , 1999, Nature Genetics.

[65]  J. Kidd,et al.  Assessing linkage disequilibrium in a complex genetic system. I. Overall deviation from random association , 1999, Annals of human genetics.

[66]  Gabor T. Marth,et al.  A global reference for human genetic variation , 2015, Nature.

[67]  Carl W. Schmid,et al.  Sequence organization of the human genome , 1975, Cell.

[68]  K. Kidd,et al.  Single nucleotide polymorphisms and haplotypes in Native American populations. , 2011, American journal of physical anthropology.

[69]  Derek E. Kelly,et al.  Loci associated with skin pigmentation identified in African populations , 2017, Science.

[70]  Carina M. Schlebusch,et al.  Extensive Population Structure in San, Khoe, and Mixed Ancestry Populations from Southern Africa Revealed by 44 Short 5-SNP Haplotypes , 2012, Human biology.

[71]  M. Florek,et al.  Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection , 1999, Bone Marrow Transplantation.

[72]  Gabriel Silva,et al.  Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America , 2009, Human mutation.

[73]  Á. Carracedo,et al.  Inference of biogeographical ancestry across central regions of Eurasia , 2015, International Journal of Legal Medicine.

[74]  M. Daly,et al.  High-resolution haplotype structure in the human genome , 2001, Nature Genetics.

[75]  John M. Butler,et al.  Fundamentals of Forensic DNA Typing , 2009 .

[76]  K. Kidd,et al.  Genetic variation in Tunisia in the context of human diversity worldwide , 2016, American journal of physical anthropology.

[77]  Andrew G Clark,et al.  Linkage disequilibrium and the mapping of complex human traits. , 2002, Trends in genetics : TIG.

[78]  Weibo Liang,et al.  Identifying novel microhaplotypes for ancestry inference , 2018, International Journal of Legal Medicine.

[79]  Anthony J Brookes,et al.  Linkage disequilibrium patterns vary substantially among populations , 2005, European Journal of Human Genetics.

[80]  Kenneth K Kidd,et al.  Significant variation in haplotype block structure but conservation in tagSNP patterns among global populations , 2007, European Journal of Human Genetics.

[81]  B. O’Roak,et al.  Haplotype evolution of SLITRK1, a candidate gene for Gilles de la Tourette Syndrome , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[82]  J. Butler.  Lineage Markers: Y Chromosome and mtDNA Testing , 2010 .

[83]  Sharon R Grossman,et al.  Integrating common and rare genetic variation in diverse human populations , 2010, Nature.

[84]  Manfred Kayser,et al.  Improving human forensics through advances in genetics, genomics and molecular biology , 2011, Nature Reviews Genetics.

[85]  K. Kidd,et al.  Candidate SNPs for a universal individual identification panel , 2007, Human Genetics.

[86]  K K Kidd,et al.  A global haplotype analysis of the myotonic dystrophy locus: implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations. , 1998, American journal of human genetics.

[87]  Kenneth K. Kidd,et al.  SNPs for a universal individual identification panel , 2010, Human Genetics.

[88]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[89]  Amanda B. Hepler,et al.  Genetic relatedness analysis: modern data and new challenges , 2006, Nature Reviews Genetics.

[90]  Michael D. Edge,et al.  Individual Identifiability Predicts Population Identifiability in Forensic Microsatellite Markers , 2016, Current Biology.

[91]  Titia Sijen,et al.  Developmental validation of the HIrisPlex system: DNA-based eye and hair colour prediction for forensic and anthropological usage. , 2014, Forensic science international. Genetics.

[92]  Haseena Rajeevan,et al.  Introducing the Forensic Research/Reference on Genetics knowledge base, FROG-kb , 2012, Investigative Genetics.

[93]  M. Skolnick,et al.  Report of the committee on human gene mapping by recombinant DNA techniques. , 1982, Birth defects original article series.

[94]  Andrew Smith.  Genome sequence of the nematode C-elegans: A platform for investigating biology , 1998 .

[95]  K. Kidd,et al.  Genetic markers for massively parallel sequencing in forensics , 2015 .

[96]  Kenneth K. Kidd,et al.  ALFRED: an allele frequency resource for research and teaching , 2011, Nucleic Acids Res..

[97]  Jonathan Scott Friedlaender,et al.  A Human Genome Diversity Cell Line Panel , 2002, Science.

[98]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[99]  Report on ISFG SNP Panel Discussion , 2008 .

[100]  K. Kidd,et al.  Progress toward an efficient panel of SNPs for ancestry inference. , 2014, Forensic science international. Genetics.

[101]  Carla Santos,et al.  Inference of Ancestry in Forensic Analysis II: Analysis of Genetic Data. , 2016, Methods in molecular biology.

[102]  Weibo Liang,et al.  NGS technology makes microhaplotype a potential forensic marker , 2015 .

[103]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[104]  Jeroen F. J. Laros,et al.  Short hypervariable microhaplotypes: A novel set of very short high discriminating power loci without stutter artefacts. , 2018, Forensic science international. Genetics.

[105]  M V Lareu,et al.  Eurasiaplex: a forensic SNP assay for differentiating European and South Asian ancestries. , 2013, Forensic science international. Genetics.

[106]  L. Wood,et al.  Haplotype Counting for Sensitive Chimerism Testing: Potential for Early Leukemia Relapse Detection. , 2017, The Journal of molecular diagnostics : JMD.

[107]  F. Collins,et al.  The Human Genome Project: Lessons from Large-Scale Biology , 2003, Science.

[108]  N. W. Davis,et al.  The complete genome sequence of Escherichia coli K-12. , 1997, Science.

[109]  Chris Phillips,et al.  Forensic genetic analysis of bio-geographical ancestry. , 2015, Forensic science international. Genetics.

[110]  D. Haussler,et al.  A physical map of the human genome , 2001, Nature.

[111]  The International HapMap Consortium.  A haplotype map of the human genome , 2005 .

[112]  Feng Chen,et al.  Evaluation of the Microhaplotypes panel for DNA mixture analyses. , 2018, Forensic science international. Genetics.

[113]  Ping Wang,et al.  A panel of 74 AISNPs: Improved ancestry inference within Eastern Asia. , 2016, Forensic science international. Genetics.

[114]  R. Fleischmann,et al.  Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. , 1995, Science.

[115]  Titia Sijen,et al.  The HIrisPlex-S system for eye, hair and skin colour prediction from DNA: Introduction and forensic developmental validation. , 2018, Forensic science international. Genetics.

[116]  A. Fraser.  An introduction to population genetic theory. By J. F. Crow and M. Kimura. Harper and Row, New York. 656 pp. 1970 , 1972 .

[117]  Titia Sijen,et al.  Developmental validation of the IrisPlex system: determination of blue and brown iris colour for forensic intelligence. , 2011, Forensic science international. Genetics.

[118]  Jong Jin Kim,et al.  The distribution and most recent common ancestor of the 17q21 inversion in humans. , 2010, American journal of human genetics.

[119]  K. Kidd,et al.  Criteria for selecting microhaplotypes: mixture detection and deconvolution , 2015, Investigative Genetics.

[120]  K. Kidd,et al.  Evaluating 130 microhaplotypes across a global set of 83 populations. , 2017, Forensic science international. Genetics.

[121]  Kevin M. Kiesler,et al.  Performance of a next generation sequencing SNP assay on degraded DNA. , 2015, Forensic science international. Genetics.

[122]  †The International HapMap Consortium.  The International HapMap Project , 2003, Nature.

[123]  Loy En Yun,et al.  Next Generation Sequencing Technologies and Their Applications , 2010 .

[124]  M. Batzer,et al.  Alu repeats and human genomic diversity , 2002, Nature Reviews Genetics.

[125]  The International HapMap Consortium,et al.  A physical map of the human genome , 2001 .

[126]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[127]  J. Stephens,et al.  Haplotype Variation and Linkage Disequilibrium in 313 Human Genes , 2001, Science.

[128]  T. Lion,et al.  Sequential monitoring of chimerism and detection of minimal residual disease after allogeneic blood stem cell transplantation (BSCT) using multiplex PCR amplification of short tandem repeat-markers , 2001, Leukemia.

[129]  Nnamdi E. Ihuegbu,et al.  Microhaplotype loci are a powerful new type of forensic marker , 2013 .

[130]  J. Berg.  Genome sequence of the nematode C. elegans: a platform for investigating biology. , 1998, Science.

[131]  K. Kidd,et al.  Mini-haplotypes as lineage informative SNPs and ancestry inference SNPs , 2012, European Journal of Human Genetics.