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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.10 P.711-720


Sequence-length variation of mtDNA HVS-I C-stretch in Chinese ethnic groups

Author(s):  Feng CHEN, Yong-hui DANG, Chun-xia YAN, Yan-ling LIU, Ya-jun DENG, David J. R. FULTON, Teng CHEN

Affiliation(s):  Department of Forensic Medicine, School of Medicine, Xi’ more

Corresponding email(s):   chenteng@mail.xjtu.edu.cn

Key Words:  Mitochondrial DNA (mtDNA), Clone sequencing, Length heteroplasmy, Population genetics

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Feng CHEN, Yong-hui DANG, Chun-xia YAN, Yan-ling LIU, Ya-jun DENG, David J. R. FULTON, Teng CHEN. Sequence-length variation of mtDNA HVS-I C-stretch in Chinese ethnic groups[J]. Journal of Zhejiang University Science B, 2009, 10(10): 711-720.

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author="Feng CHEN, Yong-hui DANG, Chun-xia YAN, Yan-ling LIU, Ya-jun DENG, David J. R. FULTON, Teng CHEN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Sequence-length variation of mtDNA HVS-I C-stretch in Chinese ethnic groups
%A Feng CHEN
%A Yong-hui DANG
%A Chun-xia YAN
%A Yan-ling LIU
%A Ya-jun DENG
%A David J. R. FULTON
%A Teng CHEN
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 10
%P 711-720
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0920140

T1 - Sequence-length variation of mtDNA HVS-I C-stretch in Chinese ethnic groups
A1 - Feng CHEN
A1 - Yong-hui DANG
A1 - Chun-xia YAN
A1 - Yan-ling LIU
A1 - Ya-jun DENG
A1 - David J. R. FULTON
A1 - Teng CHEN
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 10
SP - 711
EP - 720
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0920140

The purpose of this study was to investigate mitochondrial DNA (mtDNA) hypervariable segment-I (HVS-I) C-stretch variations and explore the significance of these variations in forensic and population genetics studies. The C-stretch sequence variation was studied in 919 unrelated individuals from 8 Chinese ethnic groups using both direct and clone sequencing approaches. Thirty eight C-stretch haplotypes were identified, and some novel and population specific haplotypes were also detected. The C-stretch genetic diversity (GD) values were relatively high, and probability (P) values were low. Additionally, C-stretch length heteroplasmy was observed in approximately 9% of individuals studied. There was a significant correlation (r=−0.961, P<0.01) between the expansion of the cytosine sequence length in the C-stretch of HVS-I and a reduction in the number of upstream adenines. These results indicate that the C-stretch could be a useful genetic maker in forensic identification of Chinese populations. The results from the Fst and dA genetic distance matrix, neighbor-joining tree, and principal component map also suggest that C-stretch could be used as a reliable genetic marker in population genetics.

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[1] Allen, M., Engstrom, A.S., Meyers, S., Handt, O., Saldeen, T., von Haeseler, A., Paabo, S., Gyllensten, U., 1998. Mitochondrial DNA sequencing of shed hairs and saliva on robbery caps: sensitivity and matching probabilities. J Forensic Sci., 43(3):453-464.

[2] Anderson, S., Bankier, A.T., Barrell, B.G., de Bruijn, M.H., Coulson, A.R., Drouin, J., Eperon, I.C., Nierlich, D.P., Roe, B.A., Sanger, F., et al., 1981. Sequence and organization of the human mitochondrial genome. Nature, 290(5806):457-465.

[3] Andrews, R.M., Kubacka, I., Chinnery, P.F., Lightowlers, R.N., Turnbull, D.M., Howell, N., 1999. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet., 23(2):147.

[4] Barbosa, A.B., da Silva, L.A., Azevedo, D.A., Balbino, V.Q., Mauricio-da-Silva, L., 2008. Mitochondrial DNA control region polymorphism in the population of Alagoas state, north-eastern Brazil. J. Forensic. Sci., 53(1):142-146.

[5] Bini, C., Pappalardo, G., 2005. mtDNA HVI length heteroplasmic profile in different tissues of maternally related members. Forensic. Sci. Int., 152(1):35-38.

[6] Bowling, A.C., Mutisya, E.M., Walker, L.C., Price, D.L., Cork, L.C., Beal, M.F., 1993. Age-dependent impairment of mitochondrial function in primate brain. J. Neurochem., 60(5):1964-1967.

[7] Brandon, M.C., Lott, M.T., Nguyen, K.C., Spolim, S., Navathe, S.B., Baldi, P., Wallace, D.C., 2005. MITOMAP: a human mitochondrial genome database—2004 update. Nucleic. Acids. Res., 33(Database Issue):D611-D613.

[8] Brown, W.M., Prager, E.M., Wang, A., Wilson, A.C., 1982. Mitochondrial DNA sequences of primates: tempo and mode of evolution. J. Mol. Evol., 18(4):225-239.

[9] Carracedo, A., Bar, W., Lincoln, P., Mayr, W., Morling, N., Olaisen, B., Schneider, P., Budowle, B., Brinkmann, B., Gill, P., et al., 2000. DNA commission of the international society for forensic genetics: guidelines for mitochondrial DNA typing. Forensic. Sci. Int., 110(2):79-85.

[10] Chen, M.H., Lee, H.M., Tzen, C.Y., 2002. Polymorphism and heteroplasmy of mitochondrial DNA in the D-loop region in Taiwanese. J. Formos. Med. Assoc., 101(4):268-276.

[11] Cooper, J.M., Mann, V.M., Schapira, A.H., 1992. Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing. J. Neurol. Sci., 113(1):91-98.

[12] Du, R., Yip, V.F., 1993. Ethnic Groups in China. Science Press, Beijing, China.

[13] Howell, N., Smejkal, C.B., 2000. Persistent heteroplasmy of a mutation in the human mtDNA control region: hypermutation as an apparent consequence of simple-repeat expansion/contraction. Am. J. Hum. Genet., 66(5):1589-1598.

[14] Imaizumi, K., Parsons, T.J., Yoshino, M., Holland, M.M., 2002. A new database of mitochondrial DNA hypervariable regions I and II sequences from 162 Japanese individuals. Int. J. Legal. Med., 116(2):68-73.

[15] Ingman, M., Kaessmann, H., Pääbo, S., Gyllensten, U., 2000. Mitochondrial genome variation and the origin of modern humans. Nature, 408(6813):708-713.

[16] Irwin, J.A., Saunier, J.L., Niederstatter, H., Strouss, K.M., Sturk, K.A., Diegoli, T.M., Brandstatter, A., Parson, W., Parsons, T.J., 2009. Investigation of heteroplasmy in the human mitochondrial DNA control region: a synthesis of observations from more than 5000 global population samples. J. Mol. Evol., 68(5):516-527.

[17] Kirches, E., Michael, M., Warich-Kirches, M., Schneider, T., Weis, S., Krause, G., Mawrin, C., Dietzmann, K., 2001. Heterogeneous tissue distribution of a mitochondrial DNA polymorphism in heteroplasmic subjects without mitochondrial disorders. J. Med. Genet., 38(5):312-317.

[18] Lee, H.C., Li, S.H., Lin, J.C., Wu, C.C., Yeh, D.C., Wei, Y.H., 2004. Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutat. Res., 547(1-2):71-78.

[19] Lee, H.Y., Chung, U., Yoo, J.E., Park, M.J., Shin, K.J., 2004. Quantitative and qualitative profiling of mitochondrial DNA length heteroplasmy. Electrophoresis, 25(1):28-34.

[20] Lee, H.Y., Chung, U., Park, M.J., Yoo, J.E., Han, G.R., Shin, K.J., 2006. Differential distribution of human mitochondrial DNA in somatic tissues and hairs. Ann. Hum. Genet., 70(Pt 1):59-65.

[21] Lutz-Bonengel, S., Sanger, T., Pollak, S., Szibor, R., 2004. Different methods to determine length heteroplasmy within the mitochondrial control region. Int. J. Legal. Med., 118(5):274-281.

[22] Lutz-Bonengel, S., Schmidt, U., Sanger, T., Heinrich, M., Schneider, P.M., Pollak, S., 2008. Analysis of mitochondrial length heteroplasmy in monozygous and non-monozygous siblings. Int. J. Legal. Med., 122(4): 315-321.

[23] Ma, Y., 1994. China’s Minority Nationalities. Foreign Languages Press, Beijing, China.

[24] Mabuchi, T., Susukida, R., Kido, A., Oya, M., 2007. Typing the 1.1 kb control region of human mitochondrial DNA in Japanese individuals. J. Forensic. Sci., 52(2):355-363.

[25] Macaulay, V., Richards, M., Hickey, E., Vega, E., Cruciani, F., Guida, V., Scozzari, R., Bonne-Tamir, B., Sykes, B., Torroni, A., 1999. The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs. Am. J. Hum. Genet., 64(1):232-249.

[26] Malik, S., Sudoyo, H., Pramoonjago, P., Sukarna, T., Darwis, D., Marzuki, S., 2002a. Evidence for the de novo regeneration of the pattern of the length heteroplasmy associated with the T16189C variant in the control (D-loop) region of mitochondrial DNA. J. Hum. Genet., 47(3): 122-130.

[27] Malik, S., Sudoyo, H., Pramoonjago, P., Suryadi, H., Sukarna, T., Njunting, M., Sahiratmadja, E., Marzuki, S., 2002b. Nuclear mitochondrial interplay in the modulation of the homopolymeric tract length heteroplasmy in the control (D-loop) region of the mitochondrial DNA. Hum. Genet., 110(5):402-411.

[28] Meierhofer, D., Mayr, J.A., Foetschl, U., Berger, A., Fink, K., Schmeller, N., Hacker, G.W., Hauser-Kronberger, C., Kofler, B., Sperl, W., 2004. Decrease of mitochondrial DNA content and energy metabolism in renal cell carcinoma. Carcinogenesis, 25(6):1005-1010.

[29] Montanini, L., Regna-Gladin, C., Eoli, M., Albarosa, R., Carrara, F., Zeviani, M., Bruzzone, M.G., Broggi, G., Boiardi, A., Finocchiaro, G., 2005. Instability of mitochondrial DNA and MRI and clinical correlations in malignant gliomas. J. Neuro-Oncol., 74(1):87-89.

[30] Nei, M., 1987. Molecular Evolutionary Genetics. Columbia University Press, New York.

[31] Nei, M., 1996. Phylogenetic analysis in molecular evolutionary genetics. Annu. Rev. Genet., 30(1):371-403.

[32] Ota, T., 1993. DISPAN: Genetic Distance and Phylogenetic Analysis. Institute of Molecular Evolutionary Genetics, Pennsylvania State University, PA, USA.

[33] Pfeiffer, H., Lutz-Bonengel, S., Pollak, S., Fimmers, R., Baur, M.P., Brinkmann, B., 2004. Mitochondrial DNA control region diversity in hairs and body fluids of monozygotic triplets. Int. J. Legal. Med., 118(2):71-74.

[34] Salas, A., Lareu, M.V., Carracedo, A., 2001. Heteroplasmy in mtDNA and the weight of evidence in forensic mtDNA analysis: a case report. Int. J. Legal. Med., 114(3): 186-190.

[35] Sangkhathat, S., Kusafuka, T., Yoneda, A., Kuroda, S., Tanaka, Y., Sakai, N., Fukuzawa, M., 2005. Renal cell carcinoma in a pediatric patient with an inherited mitochondrial mutation. Pediatr. Surg. Int., 21(9):745-748.

[36] Schneider, S., Roessli, D., Excoffier, L., 2000. Arlequin: A Software for Population Genetic Data Analysis. Genetics and Biometry Laboratory, University of Geneva, Switzerland.

[37] Stoneking, M., Hedgecock, D., Higuchi, R.G., Vigilant, L., Erlich, H.A., 1991. Population variation of human mtDNA control region sequences detected by enzymatic amplification and sequence-specific oligonucleotide probes. Am. J. Hum. Genet., 48(2):370-382.

[38] Tamura, K., Dudley, J., Nei, M., Kumar, S., 2007. MEGA4: molecular evolutionary genetics analysis. Mol. Biol. Evol., 24(8):1596-1599.

[39] Tan, D.J., Bai, R.K., Wong, L.J., 2002. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res., 62(4):972-976.

[40] Walsh, P.S., Metzger, D.A., Higuchi, R., 1991. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques, 10(4): 506-513.

[41] Watson, E., Bauer, K., Aman, R., Weiss, G., von Haeseler, A., Paabo, S., 1996. mtDNA sequence diversity in Africa. Am. J. Hum. Genet., 59(2):437-444.

[42] Yen, T.C., Chen, Y.S., King, K.L., Yeh, S.H., Wei, Y.H., 1989. Liver mitochondrial respiratory functions decline with age. Biochem. Biophys. Res. Commun., 165(3):994-1003.

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