International Journal of Legal Medicine

, Volume 118, Issue 3, pp 137–146 | Cite as

Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians

  • Michael D. Coble
  • Rebecca S. Just
  • Jennifer E. O’Callaghan
  • Ilona H. Letmanyi
  • Christine T. Peterson
  • Jodi A. Irwin
  • Thomas J. Parsons
Original Article

Abstract

We have sequenced the entire mtDNA genome (mtGenome) of 241 individuals who match 1 of 18 common European Caucasian HV1/HV2 types, to identify sites that permit additional forensic discrimination. We found that over the entire mtGenome even individuals with the same HV1/HV2 type rarely match. Restricting attention to sites that are neutral with respect to phenotypic expression, we have selected eight panels of single nucleotide polymorphism (SNP) sites that are useful for additional discrimination. These panels were selected to be suitable for multiplex SNP typing assays, with 7–11 sites per panel. The panels are specific for one or more of the common HV1/HV2 types (or closely related types), permitting a directed approach that conserves limiting case specimen extracts while providing a maximal chance for additional discrimination. Discrimination provided by the panels reduces the frequency of the most common type in the European Caucasian population from ~7% to ~2%, and the 18 common types we analyzed are resolved to 105 different types, 55 of which are seen only once.

Keywords

Human mitochondrial DNA genome Single nucleotide polymorphism Forensic DNA testing Increased forensic discrimination mtDNA coding region 

References

  1. Allard MW, Miller K, Wilson M, Monson K, Budowle B (2002) Characterization of the Caucasian haplogroups present in the SWGDAM forensic mtDNA dataset for 1771 human control region sequences. Scientific Working Group on DNA Analysis Methods. J Forensic Sci 47:1215–1223PubMedGoogle Scholar
  2. Anderson S, Bankier AT, Barrell BG et al. (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465PubMedGoogle Scholar
  3. Andreasson H, Asp A, Alderborn A, Gyllensten U, Allen M (2002) Mitochondrial sequence analysis for forensic identification using pyrosequencing technology. Biotechniques 32:124–133PubMedGoogle Scholar
  4. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N (1999) Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet 23:147PubMedGoogle Scholar
  5. Aquadro CF, Greenberg BD (1983) Human mitochondrial DNA variation and evolution: analysis of nucleotide sequences from seven individuals. Genetics 103:287–312PubMedGoogle Scholar
  6. Armstrong B, Stewart M, Mazumder A (2000) Suspension arrays for high throughput, multiplexed single nucleotide polymorphism genotyping. Cytometry 40:102–108CrossRefPubMedGoogle Scholar
  7. Bandelt HJ, Quintana-Murci L, Salas A, Macaulay V (2002) The fingerprint of phantom mutations in mitochondrial DNA data. Am J Hum Genet 71:1150–1160CrossRefPubMedGoogle Scholar
  8. Bodenteich A, Mitchell LG, Polymeropoulos MH, Merril CR (1992) Dinucleotide repeat in the human mitochondrial D-loop. Hum Mol Genet 1:140Google Scholar
  9. Brandstätter A, Parsons TJ, Niederstätter H, Parson W (2003) Rapid screening of mtDNA coding region SNPs for the identification of Caucasian haplogroups. Int J Legal Med 117:291–298CrossRefPubMedGoogle Scholar
  10. Brown MD, Shoffner JM, Kim YL et al. (1996) Mitochondrial DNA sequence analysis of four Alzheimer’s and Parkinson’s disease patients. Am J Med Genet 61:283–289CrossRefPubMedGoogle Scholar
  11. Cavelier L, Erikson I, Tammi M et al. (2002) MtDNA mutations in maternally inherited diabetes: presence of the 3397 ND1 mutation previously associated with Alzheimer’s and Parkinson’s disease. J Neuropathol Exp Neurol 61:634–639PubMedGoogle Scholar
  12. Finnila S, Lehtonen MS, Majamaa K (2001) Phylogenetic network for European mtDNA. Am J Hum Genet 68:1475–1484PubMedGoogle Scholar
  13. Gabriel MN, Calloway CD, Reynolds RL, Primorac D (2003) Identification of human remains by immobilized sequence-specific oligonucleotide probe analysis of mtDNA hypervariable regions I and II. Croatian Med J 44:293–298Google Scholar
  14. Herrnstadt C, Elson JL, Fahy E et al. (2002) Reduced-median-network analysis of complete mitochondrial DNA coding region sequences for the major African, Asian, and European haplogroups. Am J Hum Genet 70:1152–1171Google Scholar
  15. Herrnstadt C, Preston G, Howell N (2003) Errors, phantoms and otherwise, in human mtDNA sequences. Am J Hum Genet 72:1585–1586CrossRefPubMedGoogle Scholar
  16. Holland MM, Parsons TJ (1999) Mitochondrial DNA sequence analysis—Validation and use for forensic casework. Forensic Sci Rev 11:21–50Google Scholar
  17. Horai S, Hayasaka K (1990) Intraspecific nucleotide sequence differences in the major noncoding region of human mitochondrial DNA. Am J Hum Genet 46:828–842PubMedGoogle Scholar
  18. Ingman M, Gyllensten U (2003) Mitochondrial genome variation and evolutionary history of Australian and New Guinean Aborigines. Genome Res 13:1600–1606CrossRefPubMedGoogle Scholar
  19. Ingman M, Kaessmann H, Pääbo S, Gyllensten U (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408:708–713PubMedGoogle Scholar
  20. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  21. Lee MS, Levin BC (2002) MitoAnalyzer, a computer program and interactive web site to determine the effects of single nucleotide polymorphisms and mutations in human mitochondrial DNA. Mitochondrion 1:321–326CrossRefGoogle Scholar
  22. Lee SD, Lee YS, Lee JB (2002) Polymorphism in the mitochondrial cytochrome B gene in Koreans. An additional marker for individual identification. Int J Legal Med 116:74–78PubMedGoogle Scholar
  23. Levin BC, Holland KA, Hancock DK et al. (2003) Comparison of the complete mtDNA genome sequences of human cell lines—HL-60 and GM10742A—from individuals with pro-myelocytic leukemia and leber heredity optic neuropathy, respectively, and the inclusion of HL-60 in the NIST human mitochondrial DNA standard reference material—SRM 2392-I. Mitochondrion 2:387–400CrossRefGoogle Scholar
  24. Lin MT, Simon DK, Ahn CH, Kim LM, Beal MF (2002) High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer’s disease brain. Hum Mol Genet 11:133–145CrossRefPubMedGoogle Scholar
  25. Lutz S, Wittig H, Weisser HJ et al. (2000) Is it possible to differentiate mtDNA by means of HVIII in samples that cannot be distinguished by sequencing the HVI and HVII regions? Forensic Sci Int 113:97–101CrossRefPubMedGoogle Scholar
  26. Lutz-Bonengel S, Schmidt U, Schmitt T, Pollak S (2003) Sequence polymorphisms within the human mitochondrial genes MTATP6, MTATP8, and MTND4. Int J Legal Med 117:133–142PubMedGoogle Scholar
  27. Maca-Meyer N, Gonzalez AM, Larruga JM, Flores C, Cabrera VM (2001) Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2:13PubMedGoogle Scholar
  28. Macaulay V, Richards M, Hickey E et al. (1999) The emerging tree of west Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs. Am J Hum Genet 64:232–249PubMedGoogle Scholar
  29. Malyarchuk BA, Rogozin IB, Berikov VB, Derenko MV (2002) Analysis of phylogenetically reconstructed mutational spectra in human mitochondrial DNA control region. Hum Genet 111:46–53CrossRefPubMedGoogle Scholar
  30. Mehta AB, Vulliamy T, Gordon-Smith EC, Luzzatto L (1989) A new genetic polymorphism in the 16S ribosomal RNA gene of human mitochondrial DNA. Ann Hum Genet 53:303–310PubMedGoogle Scholar
  31. Meyer S, Weiss G, Haeseler A von (1999) Pattern of nucleotide substitution and rate heterogeneity in the hypervariable regions I and II of human mtDNA. Genetics 152:1103–1110PubMedGoogle Scholar
  32. Monson KL, Miller KWP, Wilson MR, DiZinno JA, Budowle B (2002) The mtDNA population database: an integrated software and database resource for forensic comparison. Forensic Sci Comm 4:2. http://www.fbi.gov/hq/lab/fsc/backissu/april2002/miller1.htm
  33. Parsons TJ, Coble MD (2001) Increasing the forensic discrimination of mitochondrial DNA testing through analysis of the entire mitochondrial DNA genome. Croatian Med J 42:304–309Google Scholar
  34. Saccone C, Pesole G, Sbisa E (1991) The main regulatory region of mammalian mitochondrial DNA: structure-function model and evolutionary pattern. J Mol Evol 33:83–91PubMedGoogle Scholar
  35. Stewart JE, Fisher CL, Aagaard PJ et al. (2001) Length variation in HV2 of the human mitochondrial DNA control region. J Forensic Sci 46:862–870PubMedGoogle Scholar
  36. Torroni A, Lott MT, Cabell MF, Chen YS, Lavergne L, Wallace DC (1994) mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region. Am J Hum Genet 55:760–776PubMedGoogle Scholar
  37. Torroni A, Huoponen K, Francalacci P et al. (1996) Classification of European mtDNAs from an analysis of three European populations. Genetics 144:1835–1850PubMedGoogle Scholar
  38. Tzen CY, Wu TY, Liu HF (2001) Sequence polymorphism in the coding region of mitochondrial genome encompassing position 8389–8865. Forensic Sci Int 120:204–209CrossRefPubMedGoogle Scholar
  39. Vallone PM, Just RS, Coble MD, Butler JM, Parsons TJ (2004) A multiplex allele-specific primer extension assay for forensically informative SNPs distributed throughout the mitochondrial genome. Int J Legal Med 118 (in press)Google Scholar
  40. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482–1488PubMedGoogle Scholar
  41. Wallace DC, Brown MD, Lott MT (1999) Mitochondrial DNA variation in human evolution and disease. Gene 238:211–230PubMedGoogle Scholar
  42. Walsh PS, Metzger DA, Higuchi R (1991) Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques 10:506–513PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Michael D. Coble
    • 1
    • 2
  • Rebecca S. Just
    • 1
  • Jennifer E. O’Callaghan
    • 1
  • Ilona H. Letmanyi
    • 1
  • Christine T. Peterson
    • 1
    • 3
  • Jodi A. Irwin
    • 1
  • Thomas J. Parsons
    • 1
  1. 1.The Armed Forces DNA Identification LaboratoryRockvilleUSA
  2. 2.The George Washington University Graduate Program in GeneticsWashingtonUSA
  3. 3.The Institute for Genomic ResearchRockvilleUSA

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