Biomics

Microhaplotypes that carry a certain number of SNPs (Single-Nucleotide Polymorphism) are a new type of markers in forensic research for DNA identification of individuals, requiring comparison of data on both paired chromosomes, which is more correctly considered as a microdiplotype analysis. The main method of identifying SNPs in microhaplotypes (microdiplotypes) is massively parallel sequencing. In comparison with individual SNP, a higher discriminating ability of SNPs within microhaplotypes considering their cis/trans relationships has been demonstrated, for family and ancestral analyses, as well as for the analysis of mixed biological samples, which is highly demanded in DNA forensics. The evolution of microhaplotypes used in DNA forensics is shown in the form of a decrease in their size with a simultaneous increase in the number of SNPs in them. Several selected microhaplotypes are presented, including both bi-, and tri- and tetraallelic SNPs flanked by genome nucleotide sequences in which polymorphic nucleotides have not yet been identified and which can serve as places for annealing primers.

DNA, single-nucleotide polymorphism, SNP, microhaplotypes, phased SNPs, cis/trans relationships of SNPs, microdiplotypes, DNA forensics, DNA identification, massively parallel sequencing, MPS

1. Anisimov V.A., Garafutdinov R.R., Sagitov A.M., Sakhabutdinova A.R., Khusnutdinova E.K., Aminev F.G., Chemeris A.V. DNA forensics – the origin, present state and future prospects. Biomics. 2019. V.11(3). P. 282-314. DOI: 10.31301/2221- 6197.bmcs.2019-26 (In Russian)
2. Bennett L., Oldoni F., Long K., Cisana S., Madella K., Wootton S., Chang J., Hasegawa R., Lagacé R., Kidd K.K., Podini D. Mixture deconvolution by massively parallel sequencing of microhaplotypes. Int. J. Legal Med. 2019. V.133(3). P.719-729. doi: 10.1007/s00414-019-02010-7
3. Brookes A.J. The essence of SNPs. Gene. 1999. V.234(2). P.177-186. doi: 10.1016/s0378- 1119(99)00219-x
4. Bulbul O., Pakstis A.J., Soundararajan U., Gurkan C., Brissenden J.E., Roscoe J.M., Evsanaa B., Togtokh A., Paschou P., Grigorenko E.L., Gurwitz D., Wootton S., Lagace R., Chang J., Speed W.C., Kidd K.K. Ancestry inference of 96 population samples using microhaplotypes. Int. J. Legal Med. 2018. V.132(3). P.703-711. doi: 10.1007/s00414-017-1748-6
5. Ceppellini R., Curtoni E.S., Mattiuz P.L., Miggiano C., Scudeller G., Serra A. Genetics of leukocyte antigens: a family study of segregation and linkage. In: Curtoni E.S., Mattiuz P.L., Tosi R.M., eds. Histocompatibility testing. Copenhagen, Munksgaard. 1967. P. 149–187.
6. Chemeris D.A., Sagitov A.M., Aminev F.G., Lutsenko V.I., Garafutdinov R.R., Sakhabutdinova A.R., Vasilov R.G., Alexeyev Ya.I., Slominsky P.A., Khusnutdinova E.K., Chemeris A.V. The evolution of approaches to DNA identification of personality. Biomics. 2018. V.10(1). P.85-140. DOI: 10.31301/2221- 6197.bmcs.2018-16 (In Russian)
7. Chen P., Deng C., Li Z., Pu Y., Yang J., Yu Y., Li K., Li D., Liang W., Zhang L., Chen F. A microhaplotypes panel for massively parallel sequencing analysis of DNA mixtures. Forensic Sci. Int. Genet. 2019. V.40. P.140-149. doi: 10.1016/j.fsigen.2019.02.018
8. Chen P., Yin C., Li Z., Pu Y., Yu Y., Zhao P., Chen D., Liang W., Zhang L., Chen F. Evaluation of the Microhaplotypes panel for DNA mixture analyses. Forensic Sci. Int. Genet. 2018. V.35. P.149-155. doi: 10.1016/j.fsigen.2018.05.003
9. Chen P., Zhu J., Pu Y., Jiang Y., Chen D., Wang H., Mao J., Zhou B., Gao L., Bai P., Liang W., Zhang L. Microhaplotype identified and performed in genetic investigation using PCR-SSCP. Forensic Sci. Int. Genet. 2017. V.28. e1-e7. doi: 10.1016/j.fsigen.2017.01.008
10. Chen P., Zhu W., Tong F., Pu Y., Yu Y., Huang S., Li Z., Zhang L., Liang W., Chen F. Identifying novel microhaplotypes for ancestry inference. Int. J. Legal Med. 2019. V.133(4). P.983-988. doi: 10.1007/s00414- 018-1881-x
11. Daly M.J., Rioux J.D., Schaffner S.F., Hudson T.J., Lander E.S. High-resolution haplotype structure in the human genome. Nat. Genet. 2001. V.29(2). P.229- 232. doi: 10.1038/ng1001-229
12. de la Puente M., Phillips C., Xavier C., Amigo J., Carracedo A., Parson W., Lareu M.V. Building a custom large-scale panel of novel microhaplotypes for forensic identification using MiSeq and Ion S5 massively parallel sequencing systems. Forensic Sci. Int. Genet. 2020. V.45. P.102213. doi: 10.1016/j.fsigen.2019.102213
13. Devesse L., Davenport L., Borsuk L., Gettings K., Mason-Buck G., Vallone P.M., Syndercombe Court D., Ballard D. Classification of STR allelic variation using massively parallel sequencing and assessment of flanking region power. Forensic Sci Int Genet. 2020. V.48. P.102356. doi: 10.1016/j.fsigen.2020.102356
14. Eitan Y., Kashi Y. Direct micro-haplotyping by multiple double PCR amplifications of specific alleles (MD-PASA). Nucleic Acids Res. 2002. V.30(12). e62. doi: 10.1093/nar/gnf062
15. Gabriel S.B., Schaffner S.F., Nguyen H., Moore J.M., Roy J, Blumenstiel B., Higgins J., DeFelice M., Lochner A., Faggart M., Liu-Cordero S.N., Rotimi C., Adeyemo A., Cooper R., Ward R, Lander E.S., Daly M.J., Altshuler D. The structure of haplotype blocks in the human genome. Science. 2002. V.296(5576). P.2225-2229. doi: 10.1126/science.1069424
16. Gandotra N., Speed W.C., Qin W., Tang Y., Pakstis A.J., Kidd K.K., Scharfe C. Validation of novel forensic DNA markers using multiplex microhaplotype sequencing. Forensic Sci. Int. Genet. 2020. V.47. 102275. doi: 10.1016/j.fsigen.2020.102275
17. Garafutdinov R.R., Mavzyutov A.R., Alekseev Ya.I., Vorobiev A.A., Nikonorov Yu.M., Chubukova O.V., Matniyazov R.T., Baimiev An.Kh., Maksimov I.V., Kuluev B.R., Baimiev Al.Kh., Chemeris A.V. Human betacoronaviruses and their highly sensitive detection using PCR and other amplification methods. Biomics. 2020. V.12 (1). P. 121-179. doi: 10.31301/2221-6197.bmcs.2020-7 (In Russian)
18. Garafutdinov R.R., Mavzyutov A.R., Nikonorov Yu.M., Chubukova O.V., Matniyazov R.T., Baymiev An.Kh., Maksimov I.V., Miftakhov I.Yu., Kuluev B.R., Baymiev Al.Kh., Chemeris A.V. Betacoronavirus SARS-CoV-2, its genome, variety of genotypes and molecular-biological approaches to combat it. Biomics. 2020. V.12(2). P. 218-247. DOI: 10.31301/2221- 6197.bmcs.2020-12 (In Russian)
19. Garafutdinov R.R., Sakhabutdinova A.R., Slominsky P.A., Aminev F.G., Chemeris A.V. A new digital approach to SNP encoding for DNA identification. Forensic Science International. 2020. In press.
20. Garafutdinov R.R., Sakhabutdinova A.R., Vasilov R.G., Chemeris A.V Genetic barcoding related individuals. Yu.A.Ovchinnikov Bulletin of Biotechnology and Physical and Chemical Biology. 2015. V.11(2). P.20-26. (In Russian)
21. Ge J., Budowle B., Planz J.V., Chakraborty R. Haplotype block: a new type of forensic DNA markers. Int. J. Legal Med. 2010. V.124(5). P.353-361. doi: 10.1007/s00414-009-0400-5
22. Hiroaki N. , Koji F, Tetsushi K, Kazumasa S, Hiroaki N., Kazuyuki S. Approaches for identifying multiple-SNP haplotype blocks for use in human identification. Leg Med (Tokyo). 2015. V.17(5). P.415- 420. doi: 10.1016/j.legalmed.2015.06.003
23. Jones B., Walsh D., Werner L., Fiumera A. Using blocks of linked single nucleotide polymorphisms as highly polymorphic genetic markers for parentage analysis. Mol. Ecol. Resour. 2009. V.9(2). P.487-497. doi: 10.1111/j.1755-0998.2008.02444.x
24. Judson R., Stephens J.C., Windemuth A. The predictive power of haplotypes in clinical response. Pharmacogenomics. 2000. V.1(1). P.15-26. doi: 10.1517/14622416.1.1.15
25. International HapMap Consortium. The International HapMap Project. Nature. 2003. V.426(6968). P. 789-796. doi: 10.1038/nature02168
26. International HapMap Consortium. A haplotype map of the human genome. Nature. 2005. V.437(7063). P.1299-1320. doi: 10.1038/nature04226
27. International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature. 2007. V.449(7164). P.851-861. doi: 10.1038/nature06258
28. Kidd K.K. Proposed nomenclature for microhaplotypes. Hum Genomics. 2016. V.10(1). P.16. doi: 10.1186/s40246-016-0078-y
29. Kidd K.K., Kidd J.R., Speed W.C., Fang R., Furtado M.R., Hyland F.C.L., Pakstis A.J. Expanding data and resources for forensic use of SNPs in individual identification. Forensic Sci. Int. Genet. 2012. V.6(5). P.646-652. doi: 10.1016/j.fsigen.2012.02.012
30. Kidd K.K., Pakstis A.J., Speed W.C., Lagace R., Chang J., Wootton S., Ihuegbu N. Microhaplotype loci are a powerful new type of forensic marker. Forensic Science International Genetics Supplement Series. 2013. V.4(1). e123-e124. DOI: 10.1016/j.fsigss.2013.10.063
31. Kidd KK, Pakstis AJ, Speed WC, Lagacé R, Chang J, Wootton S, Haigh E, Kidd JR. Current sequencing technology makes microhaplotypes a powerful new type of genetic marker for forensics. Forensic Science International: Genetics. 2014. V. 12. P. 215-224. doi: 10.1016/j.fsigen.2014.06.014
32. Kidd K.K., Pakstis A.J., Speed W.C., Lagace R., Wootton S., Chang J. Selecting microhaplotypes optimized for different purposes. Electrophoresis. 2018. V.39(21). P.2815-2823. doi: 10.1002/elps.201800092
33. Kidd K.K., Speed W.C. Criteria for selecting microhaplotypes: mixture detection and deconvolution. Investig Genet. 2015. V.6:1. doi: 10.1186/s13323-014- 0018-3
34. Kidd KK, Speed WC, Pakstis AJ, Podini DS, Lagacé R, Chang J, Wootton S, Haigh E, Soundararajan U. Evaluating 130 microhaplotypes across a global set of 83 populations. Forensic Science International: Genetics. 2017. V. 29. P. 29-37. doi: 10.1016/j.fsigen.2017.03.014
35. Kidd K.K., Speed W.C., Wootton S., Lagace R. Langit R., Haigh E., Chang J., Pakstis A.J. Genetic markers for massively parallel sequencing in forensics. Forensic Science International: Genetics Supplement Series. 2015. V.5.P. e677-e679. doi: 10.1016/j.fsigss.2015.12.004
36. Kureshi A., Li J., Wen D., Sun S., Yang Z., Zha L. Construction and forensic application of 20 highly polymorphic microhaplotypes. Royal Soc. Open Sci. 2020. V.7(5). P.191937. doi: 10.1098/rsos.191937
37. Levy S., Sutton G., Ng P.C., Feuk L., Halpern A.L., Walenz B.P., Axelrod N., Huang J., Kirkness E.F., Denisov G., Lin Y., MacDonald J.R., Pang A.W., Shago M., Stockwell T.B., Tsiamouri A., Bafna V., Bansal V., Kravitz S.A., Busam D.A., Beeson K.Y., McIntosh T.C., Remington K.A., Abril J.F., Gill J., Borman J., Rogers Y.H., Frazier M.E., Scherer S.W., Strausberg R.L., Venter J.C. The diploid genome sequence of an individual human. PLoS Biol. 2007. V.5(10). e254. doi: 10.1371/journal.pbio.0050254
38. Li W.H., Sadler L.A. Low nucleotide diversity in man. Genetics. 1991. V.129(2). P.513-523.
39. Li Z., Yang J., Liang W., Zhang L., Chen F., Chen P. Application of MHanalyser software in the study of microhaplotypes in forensics. Forensic Science International: Genetics Supplement Series. 2019. V.7(1). P.271-273. doi: 10.1016/j.fsigss.2019.09.104
40. Mustafin R.N., Khusnutdinova E.K. COVID-19 mysteries and possible ways of their solution. Herald of the Academy of Sciences of the Republic of Bashkortostan. 2020. V.35(2). P.92-101. DOI: 10.24411/1728-5283-2020-10211 (In Russian)
41. Novroski N.M.M., Wendt F.R., Woerner A.E., Bus M.M., Coble M., Budowle B. Expanding beyond the current core STR loci: An exploration of 73 STR markers with increased diversity for enhanced DNA mixture deconvolution. Forensic Sci Int Genet. 2019. V.38. P.121-129. doi: 10.1016/j.fsigen.2018.10.013
42. Oldoni F., Kidd K.K., Podini D. Microhaplotypes in forensic genetics. Forensic Sci Int Genet. 2019. V.38. P.54-69. doi: 10.1016/j.fsigen.2018.09.009
43. Pakstis A.J., Fang R., Furtado M.R., Kidd J.R., Kidd K.K. Mini-haplotypes as lineage informative SNPs and ancestry inference SNPs. Eur. J. Hum. Genet. 2012. V.20(11). P.1148-1154. doi: 10.1038/ejhg.2012.69
44. Pang J-B., Rao M., Chen Q-F., Ji A-Q., Zhang C., Kang K-L., Wu H., Ye J., Nie S-J., Wang L. A 124- plex Microhaplotype Panel Based on Next-generation Sequencing Developed for Forensic Applications. Sci. Rep. 2020. V.10(1). P.1945. doi: 10.1038/s41598-020- 58980-x
45. Pendleton M., Sebra R., Pang A.W., Ummat A., Franzen O., Rausch T., Stütz A.M., Stedman W., Anantharaman T., Hastie A., Dai H., Fritz M.H., Cao H., Cohain A., Deikus G., Durrett R.E., Blanchard S.C., Altman R., Chin C.S., Guo Y., Paxinos E.E., Korbel J.O., Darnell R.B., McCombie W.R., Kwok P.Y., Mason C.E., Schadt E.E., Bashir A. Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nat. Methods. 2015. V.12(8). P.780-786. doi: 10.1038/nmeth.3454
46. Petersdorf E.W. In celebration of Ruggero Ceppellini: HLA in transplantation. HLA. 2017. V.89(2). P.71-76. doi: 10.1111/tan.12955
47. Soifer I., Fong N.L., Yi N., Ireland A.T., Lam I., Sooknah M., Paw J.S., Peluso P., Concepcion G.T., Rank D., Hastie A.R., Jojic V., Ruby J.G., Botstein D., Roy M.A. Fully phased sequence of a diploid human genome determined de novo from the DNA of a single individual. G3 (Bethesda). 2020. Jul 6;g3.400995.2019. doi: 10.1534/g3.119.400995
48. Stephens M., Donnelly P. A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am. J. Hum. Genet. 2003. V.73(5). P.1162-1169. doi: 10.1086/379378
49. Stephens M., Smith N.J., Donnelly P. A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 2001. V.68(4). P.978-989. doi: 10.1086/319501
50. Sun S., Liu Y., Li J., Yang Z., Wen D., Liang W., Yan Y., Yu H., Cai J., Zha L. Development and application of a nonbinary SNP-based microhaplotype panel for paternity testing involving close relatives. Forensic Sci. Int. Genet. 2020. V.46. P.102255. doi: 10.1016/j.fsigen.2020.102255
51. Turchi C., Melchionda F., Pesaresi M., Tagliabracci A. Evaluation of a microhaplotypes panel for forensic genetics using massive parallel sequencing technology. Forensic Sci Int Genet. 2019. V.41. P.120- 127. doi: 10.1016/j.fsigen.2019.04.009
52. van der Gaag K.J., de Leeuw R.H., Laros J.F.J., den Dunnen J.T., de Knijff P. Short hypervariable microhaplotypes: A novel set of very short high discriminating power loci without stutter artefacts. Forensic Sci. Int. Genet. 2018. V.35. P.169-175. doi: 10.1016/j.fsigen.2018.05.008
53. Venter J.C. Multiple personal genomes await. Nature. 2010. V.464(7289). P.676-677. doi: 10.1038/464676a
54. Voskoboinik L., Motro U., Darvasi A. Facilitating complex DNA mixture interpretation by sequencing highly polymorphic haplotypes. Forensic Sci. Int. Genet. 2018. V.35. P.136-140. doi: 10.1016/j.fsigen.2018.05.001
55. Wang H. Zhu J., Zhou N., Jiang Y., Wang L., He W., Peng D., Su Q., Ma J., Chen D., Liang W., Zhang L. NGS technology makes microhaplotype a potential forensic marker. Forensic Science International: Genetics Supplement Series. 2015. V.5. P. e233-e234. doi: 10.1016/j.fsigss.2015.09.093
56. Zhang C., Cao Y-D., Song J-J., Rao M., Nie SJ., Zhang G-F., Kang, K-L., Ji A-Q., Ye J., Wang L. MHTyper: a microhaplotype allele-calling pipeline for use with next generation sequencing data. Australian Journal of Forensic Sciences. 2019. doi: 10.1080/00450618.2019.1699956
57. Zhang R., Tan Y., Jian H., Qu S., Liu Y., Zhu J., Wang L., Lv M., Liao M., Zhang L., Yang F., Liang W. A new approach to detect a set of SNP-SNP markers: Combining ARMS-PCR with SNaPshot technology. Electrophoresis. 2020. V.41(13-14). P.1189-1197. doi: 10.1002/elps.202000009
58. Zhu J., Chen P., Qu S., Wang Y., Jian H., Cao S., Liu Y., Zhang R., Lv M., Liang W., Zhang L. Evaluation of the microhaplotype markers in kinship analysis. Electrophoresis. 2019. V.40(7). P.1091-1095. doi: 10.1002/elps.201800351
59. Zhu J., Long B., Qu S., Yin L., He W., Mao J., Wang H., Zhang L., Jin B., Chen D., Liang W. A new proposed nomenclature for microhaplotypes. Forensic Science International: Genetics Supplement Series. 2019a. V.7(1). P. 813-815. doi: 10.1016/j.fsigss.2019.10.186
60. Zhu J., Lv M., Zhou N., Chen D., Jiang Y., Wang L., He W., Peng D., Li Z., Qu S., Wang Y., Wang H., Luo H., An G., Liang W., Zhang L. Genotyping polymorphic microhaplotype markers through the Illumina(®) MiSeq platform for forensics. Forensic Sci. Int. Genet. 2019b. V.39. P.1-7. doi: 10.1016/j.fsigen.2018.11.005
61. Zhu J., Zhou N., Jiang Y., Wang L., He W., Peng D., Su Q., Mao J., Chen D., Liang W., Zhang L., FLfinder: A novel software for the microhaplotype marker. Forensic Science International: Genetics Supplement Series. 2015. V.5. P. e622-e624. doi: 10.1016/j.fsigss.2015.10.002