Abstract
Sequence analysis of the human mitochondrial genome (mtDNA) has proven to be a valuable tool in forensic identity testing and the analysis of crime scene stains. In contrast to the very expensive sequencing technique, typing of different length variants can greatly facilitate screening of a large number of traces for their relevance during casework. Within the mitochondrial control region, a dinucleotide (CA) n repeat locus is present. To assess the discrimination power of this marker, we have determined (CA) n allele distribution and the frequency of heteroplasmy in a population sample of 2,458 Germans. The inclination to develop heteroplasmic mixtures (CA) n /(CA) n−1 was positively correlated with the number of CA repeats in the mtDNA. In addition, we have studied the inheritance patterns of (CA) n repeat sequence heteroplasmy in two pedigrees. In one pedigree, we also found a length heteroplasmy in the homopolymeric C-tract (nt 303–309). Our data show stable inheritance of heteroplasmy within the homopolymeric C-stretch, but rather unstable inheritance regarding the (CA) n repeat locus.
References
Anderson S, Bankier AT, Barrell BG et al (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465
Bär W, Brinkmann B, Budowle B et al (2000) DNA Commission of the International Society for Forensic Genetics: guidelines for mitochondrial DNA typing. Int J Legal Med 113:193–196
Bendall KE, Sykes BC (1995) Length heteroplasmy in the first hypervariable segment of the human mtDNA control region. Am J Hum Genet 57:248–256
Bendall KE, Macaulay VA, Baker JR, Sykes BC (1996) Heteroplasmic point mutations in the human mtDNA control region. Am J Hum Genet 59:1276–1287
Bendall KE, Macaulay VA, Sykes BC (1997) Variable levels of a heteroplasmic point mutation in individual hair roots. Am J Hum Genet 61:1303–1308
Bodenteich A, Mitchell LG, Polymeropoulos MH, Merril CR (1992) Dinucleotide repeat in the human mitochondrial D-loop. Hum Mol Genet 1:140
Brinkmann B, Klintschar M, Neuhuber F, Hühne J, Rolf B (1998) Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet 62:1408–1415
Butler JM, Wilson MR, Reeder DJ (1998) Rapid mitochondrial DNA typing using restriction enzyme digestion of polymerase chain reaction amplicons followed by capillary electrophoresis separation with laser-induced fluorescence detection. Electrophoresis 19:119–124
Cali F, Le Roux MG, D’Anna R et al V (2001) MtDNA control region and RFLP data for Sicily and France. Int J Legal Med 114: 229–231
Cavelier L, Jazin E, Jalonen P, Gyllensten U (2000) MtDNA substitution rate and segregation of heteroplasmy in coding and noncoding regions. Hum Genet 107:45–50
Chung U, Lee HY, Yoo JE, Park MJ, Shin KJ (2005) Mitochondrial DNA CA dinucleotide repeats in Koreans: the presence of length heteroplasmy. Int J Legal Med 119:50–53
Forster P (2004) Ice ages and the mitochondrial DNA chronology of human dispersals: a review. The Royal Society (Published online 13 January 2004)
Gill P, Ivanov PL, Kimpton C et al (1994) Identification of the remains of the Romanov family by DNA analysis. Nat Genet 6:130–135
Gocke CD, Benko FA, Rogan PK (1998) Transmission of mitochondrial DNA heteroplasmy in normal pedigrees. Hum Genet 102:182–186
Hopgood R, Sullivan KM, Gill P (1992) Strategies for automated sequencing of human mitochondrial DNA directly from PCR products. Biotechniques 13:82–92
Howell N, Halvorson S, Kubacka I et al (1992) Mitochondrial gene segregation in mammals: is the bottleneck always narrow? Hum Genet 90:117–120
Howell N, Kubacka I, Mackey DA (1996) How rapidly does the human mitochondrial genome evolve? Am J Hum Genet 59:501–509
Hühne J, Pfeiffer H, Brinkmann B (1999) Heteroplasmic substitutions in the mitochondrial DNA control region in mother and child samples. Int J Legal Med 112:27–30
Lutz S, Weisser HJ, Heizmann J, Pollak S (1996) mtDNA as a tool for identification of human remains. Identification using mtDNA. Int J Legal Med 109:205–209
Lutz S, Weisser HJ, Heizmann J, Pollak S (1997) A third hypervariable region in the human mitochondrial D-loop. Hum Genet 101:384
Lutz S, Weisser HJ, Heizmann J, Pollak S (2000) Mitochondrial heteroplasmy among maternally related individuals. Int J Legal Med 113:155–161
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 113:97–101
Marchington DR, Poulton J, Sellar A, Holt IJ (1996) Do sequence variants in the major non-coding region of the mitochondrial genome influence mitochondrial mutations associated with disease? Hum Mol Genet 5:473–479
Orrego C, King, MC (1991) Determination of familiar relationship. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds) A guide to methods and application PCR protocols. Academic, San Diego, pp 416–426
Parson W, Parsons TJ, Scheithauer R, Holland MM (1998) Population data for 101 Austrian Caucasian mitochondrial DNA d-loop sequences: application of mtDNA sequence analysis to a forensic case. Int J Legal Med 111:124–132
Parsons TJ, Muniec DS, Sullivan K et al (1997) A high observed substitution rate in the human mitochondrial DNA control region. Nat Genet 15:363–368
Stewart JE, Fisher CL, Aagaard PJ et al (2001) Length variation in HV2 of the human mitochondrial DNA control region. J Forensic Sci 46:862–870
Sullivan KM, Hopgood R, Lang B, Gill P (1991) Automated amplification and sequencing of human mitochondrial DNA. Electrophoresis 12:17–21
Sullivan KM, Hopgood R, Gill P (1992) Identification of human remains by amplification and automated sequencing of mitochondrial DNA. Int J Legal Med 105:83–86
Szibor R, Michael M, Spitsyn VA et al (1997) Mitochondrial D-loop 3′ (CA) n repeat polymorphism: optimization of analysis and population data. Electrophoresis 18:2857–2860
Szibor R, Michael M, Plate I, Krause D (2000) Efficiency of forensic mtDNA analysis. Case examples demonstrating the identification of traces. Forensic Sci Int 113:71–78
Szibor R, Michael M, Plate I, Wittig H, Krause D (2003) Identification of the minor component of a mixed stain by using mismatch primer-induced restriction sites in amplified mtDNA. Int J Legal Med 117:160–164
Szibor R, Plate I, Schmitter H, Wittig H, Krause D (2006) Forensic mass screening using mt DNA. Int J Legal Med DOI 10.1007/s00414-006-0085-y
Wilson MR, Polanskey D, Replogle J et al (1997) A family exhibiting heteroplasmy in the human mitochondrial DNA control region reveals both somatic mosaicism and pronounced segregation of mitotypes. Hum Genet 100:167–171
Wilson MR, Allard MW, Monson K et al (2002) Recommendations for consistent treatment of length variants in the human mitochondrial DNA control region. Forensic Sci Int 129:35–42
Acknowledgement
We thank Dr. Bernhard Bonengel for carefully reviewing this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Szibor, R., Plate, I., Heinrich, M. et al. Mitochondrial D-loop (CA) n repeat length heteroplasmy: frequency in a German population sample and inheritance studies in two pedigrees. Int J Legal Med 121, 207–213 (2007). https://doi.org/10.1007/s00414-006-0096-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00414-006-0096-8