http://informahealthcare.com/mdn ISSN: 1940-1736 (print), 1940-1744 (electronic) Mitochondrial DNA, Early Online: 1–2 ! 2014 Informa UK Ltd. DOI: 10.3109/19401736.2014.974160
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the liver cancer model inbred C57BL/6 mice strain Sen Lu1, Yuan-yuan Gao2, Wen-yu Shao1, Guo-yong Han3, Wen-zhou Ding3, and Xin-li Huang1 Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China, 2Department of General Surgery, Changzhou No.2 People’s Hospital, Changzhou, Jiangsu Province, P.R. China, and 3Department of General Surgery, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
Mitochondrial DNA Downloaded from informahealthcare.com by McMaster University on 12/22/14 For personal use only.
1
Abstract
Keywords
In the present work, we undertook the complete mitochondrial genome sequencing of an important liver cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.
Genome, liver cancer, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In liver cancer research, animal models have allowed the study of liver cancer disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of liver cancer disease and the effects of drug intervention (Bour et al., 2014). Hepatocellular carcinoma (HCC) remains the fifth leading cause of cancer-related death worldwide and the second most common malignancy in China. Moreover, HCC is often diagnosed at a late stage and the prognosis is poor. Recent studies highlight new molecular mechanisms involved in HCC pathogenesis, including consequence of cumulative genetic and epigenetic events. Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor related death and hepatitis B virus (HBV) is associated with 70% of all HCC cases world-wide. The patients with HCC mostly have underlying chronic liver disease including liver cirrhosis (Ling et al., 2014; Yu & Kim, 2014). Unlike other solid tumors, the prognosis of patients with HCC is influenced not only by intrahepatic tumor status, but also by underlying liver function (Ling et al., 2014; Yu & Kim, 2014). Inbred rat and mouse strains with variations in their mitochondrial genomic sequences serve as good substrates for construction of conplastic strains for examining genetic contributions. Several complex traits are controlled by genetic elements of the mitochondrial genome (Zhu et al., 2014).
History Received 28 September 2014 Accepted 5 October 2014 Published online 28 October 2014
Here, we reported complete mitochondrial genome sequence of an liver cancer inbred C57BL/6 mice model. Total DNA was extracted from the liver cancer tissue of a female individual that harboring a serious liver cancer. Polymerase chain reaction (PCR) was carried out using 22 pairs of primers to amplify the entire mitochondrial genome. Mitochondrial DNA information of this strain is described in the Table 1 and sequence from the current study were deposited in GenBank (Accession No. KJ939361). The mitochondrial genome was 16,308 bp long including 13 proteincoding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The total length of the protein-coding gene sequences was 11,437 bp. Most protein-coding genes initiated with ATG except for ND2, ND3 and ND5 which begin with ATA. Eight proteincoding genes terminated with TAA whereas the ND2, ND3 and COX3 genes terminated with TAG and the CytB gene terminated with AGA. The incomplete stop codon (T– –) is used in ND4. A strong bias against G at the third codon position is observed in the protein-coding genes. The length of tRNA genes varied from 60 to 73 bp. Sequence data obtained from the current study were compared with the reference BN sequence (AC_000022.1). Eighty-nine variations in mtDNA were observed between these two strains. 35.5% of the variations were within gene-coding sequences, 18.7% were within non-coding RNA sequences, and 45.8% were synonymous variants.
Correspondence: Xin-li Huang, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210000, P.R. China. E-mail: [email protected]
2
S. Lu et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Genes encoded by this mitochondrial genome. Position Gene
Mitochondrial DNA Downloaded from informahealthcare.com by McMaster University on 12/22/14 For personal use only.
Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln tRNAMet ND2 tRNATrp tRNAAla tRNAAsn OL tRNACys tRNATyr COX1 tRNASer tRNAAsp COX2 tRNALys ATP8 ATP6 COX3 tRNAGly ND3 tRNAArg ND4L ND4 tRNAHis tRNASer tRNALeu ND5 ND6 tRNAGlu CytB tRNAThr tRNAPro
Base composition (%)
From
To
Size (bp)
A
C
G
T
362 432 1388 1455 3025 3102 4058 4124 4198 4267 5309 5377 5447 5520 5552 5619 5688 7230 7306 7375 8065 8130 8291 8971 9755 9824 10,171 10,240 10,530 11,908 11,978 12,039 12,110 13,914 14,442 14,515 15,658 15,727
429 1386 1454 3024 3099 4058 4126 4195 4266 5310 5375 5445 5519 5550 5618 5686 7232 7298 7373 8058 8127 8330 8971 9774 9823 10,180 10,239 10,536 11,907 11,977 12,037 12,109 13,930 14,441 14,510 15,654 15,727 15,789
67 955 67 1570 75 957 69 72 69 1044 67 69 73 31 67 68 1545 69 68 684 63 201 681 804 69 357 69 297 1378 70 60 71 1821 528 69 1140 70 66
35.8 36.8 38.8 37.7 33.3 31.9 40.6 25.0 27.5 36.4 37.3 27.6 23.3 35.5 25.4 33.8 28.8 26.1 36.8 34.2 34.9 39.8 33.6 26.5 31.9 30.3 40.6 32.3 32.3 41.4 31.7 38.0 32.7 22.2 29.0 31.2 34.3 24.2
25.4 22.7 19.4 21.0 21.3 27.9 13.0 9.7 24.6 26.4 20.9 10.1 16.4 29.0 20.9 16.2 25.3 14.5 13.2 23.8 17.5 23.9 27.4 28.7 18.8 29.4 10.1 24.6 28.2 15.7 18.3 14.1 29.3 8.7 11.6 30.2 21.4 13.7
17.9 18.0 11.9 17.7 16.0 12.6 14.5 29.2 18.9 8.9 16.4 23.2 31.5 25.8 25.4 20.6 16.3 27.5 17.6 14.6 17.5 7.9 11.1 14.8 16.0 12.9 10.1 11.5 10.9 8.6 16.7 18.3 10.5 28.2 20.3 13.4 17.1 28.8
20.9 22.5 29.9 23.6 29.4 27.6 31.9 36.1 29.0 28.3 25.4 39.1 28.8 9.7 28.3 29.4 29.6 31.9 32.4 27.4 30.1 28.4 27.9 30.0 33.3 27.4 39.2 31.6 28.6 34.3 33.3 29.6 27.5 40.9 39.1 25.2 27.2 33.3
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Reference Bour G, Martel F, Goffin L, Bayle B, Gangloff J, Aprahamian M, Marescaux J, Egly JM. (2014). Design and development of a robotized system coupled to microct imaging for intratumoral drug evaluation in a hcc mouse model. PLoS One 9:e106675.
Start codon
Stop codon
ATG
TAA
ATA
TAG
ATG
TAA
ATG
TAA
ATG ATG ATG
TAA TAA TAG
ATA
TAG
ATG ATG
TAA T– –
ATA ATG
TAA TAA
ATG
AGA
Strand H H H H H H H L H H H L L L L L H L H H H H H H H H H H H H H H H L L H H L
Ling Q, Shi W, Huang C, Zheng J, Cheng Q, Yu K, Chen S, et al. (2014). Epigenetic silencing of dual oxidase 1 by promoter hypermethylation in human hepatocellular carcinoma. Am J Cancer Res 4:508–17. Yu SJ, Kim YJ. (2014). Hepatitis B viral load affects prognosis of hepatocellular carcinoma. World J Gastroenterol 20: 12039–44. Zhu R, Meng ZL, Chen L, Chen W, Wang H, Hong YQ. (2014). Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus). Mitochondrial DNA. [Epub ahead of print].
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the liver cancer model inbred C57BL/6 mice strain Sen Lu1, Yuan-yuan Gao2, Wen-yu Shao1, Guo-yong Han3, Wen-zhou Ding3, and Xin-li Huang1 Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China, 2Department of General Surgery, Changzhou No.2 People’s Hospital, Changzhou, Jiangsu Province, P.R. China, and 3Department of General Surgery, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
Mitochondrial DNA Downloaded from informahealthcare.com by McMaster University on 12/22/14 For personal use only.
1
Abstract
Keywords
In the present work, we undertook the complete mitochondrial genome sequencing of an important liver cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.
Genome, liver cancer, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In liver cancer research, animal models have allowed the study of liver cancer disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of liver cancer disease and the effects of drug intervention (Bour et al., 2014). Hepatocellular carcinoma (HCC) remains the fifth leading cause of cancer-related death worldwide and the second most common malignancy in China. Moreover, HCC is often diagnosed at a late stage and the prognosis is poor. Recent studies highlight new molecular mechanisms involved in HCC pathogenesis, including consequence of cumulative genetic and epigenetic events. Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor related death and hepatitis B virus (HBV) is associated with 70% of all HCC cases world-wide. The patients with HCC mostly have underlying chronic liver disease including liver cirrhosis (Ling et al., 2014; Yu & Kim, 2014). Unlike other solid tumors, the prognosis of patients with HCC is influenced not only by intrahepatic tumor status, but also by underlying liver function (Ling et al., 2014; Yu & Kim, 2014). Inbred rat and mouse strains with variations in their mitochondrial genomic sequences serve as good substrates for construction of conplastic strains for examining genetic contributions. Several complex traits are controlled by genetic elements of the mitochondrial genome (Zhu et al., 2014).
History Received 28 September 2014 Accepted 5 October 2014 Published online 28 October 2014
Here, we reported complete mitochondrial genome sequence of an liver cancer inbred C57BL/6 mice model. Total DNA was extracted from the liver cancer tissue of a female individual that harboring a serious liver cancer. Polymerase chain reaction (PCR) was carried out using 22 pairs of primers to amplify the entire mitochondrial genome. Mitochondrial DNA information of this strain is described in the Table 1 and sequence from the current study were deposited in GenBank (Accession No. KJ939361). The mitochondrial genome was 16,308 bp long including 13 proteincoding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The total length of the protein-coding gene sequences was 11,437 bp. Most protein-coding genes initiated with ATG except for ND2, ND3 and ND5 which begin with ATA. Eight proteincoding genes terminated with TAA whereas the ND2, ND3 and COX3 genes terminated with TAG and the CytB gene terminated with AGA. The incomplete stop codon (T– –) is used in ND4. A strong bias against G at the third codon position is observed in the protein-coding genes. The length of tRNA genes varied from 60 to 73 bp. Sequence data obtained from the current study were compared with the reference BN sequence (AC_000022.1). Eighty-nine variations in mtDNA were observed between these two strains. 35.5% of the variations were within gene-coding sequences, 18.7% were within non-coding RNA sequences, and 45.8% were synonymous variants.
Correspondence: Xin-li Huang, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210000, P.R. China. E-mail: [email protected]
2
S. Lu et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Genes encoded by this mitochondrial genome. Position Gene
Mitochondrial DNA Downloaded from informahealthcare.com by McMaster University on 12/22/14 For personal use only.
Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln tRNAMet ND2 tRNATrp tRNAAla tRNAAsn OL tRNACys tRNATyr COX1 tRNASer tRNAAsp COX2 tRNALys ATP8 ATP6 COX3 tRNAGly ND3 tRNAArg ND4L ND4 tRNAHis tRNASer tRNALeu ND5 ND6 tRNAGlu CytB tRNAThr tRNAPro
Base composition (%)
From
To
Size (bp)
A
C
G
T
362 432 1388 1455 3025 3102 4058 4124 4198 4267 5309 5377 5447 5520 5552 5619 5688 7230 7306 7375 8065 8130 8291 8971 9755 9824 10,171 10,240 10,530 11,908 11,978 12,039 12,110 13,914 14,442 14,515 15,658 15,727
429 1386 1454 3024 3099 4058 4126 4195 4266 5310 5375 5445 5519 5550 5618 5686 7232 7298 7373 8058 8127 8330 8971 9774 9823 10,180 10,239 10,536 11,907 11,977 12,037 12,109 13,930 14,441 14,510 15,654 15,727 15,789
67 955 67 1570 75 957 69 72 69 1044 67 69 73 31 67 68 1545 69 68 684 63 201 681 804 69 357 69 297 1378 70 60 71 1821 528 69 1140 70 66
35.8 36.8 38.8 37.7 33.3 31.9 40.6 25.0 27.5 36.4 37.3 27.6 23.3 35.5 25.4 33.8 28.8 26.1 36.8 34.2 34.9 39.8 33.6 26.5 31.9 30.3 40.6 32.3 32.3 41.4 31.7 38.0 32.7 22.2 29.0 31.2 34.3 24.2
25.4 22.7 19.4 21.0 21.3 27.9 13.0 9.7 24.6 26.4 20.9 10.1 16.4 29.0 20.9 16.2 25.3 14.5 13.2 23.8 17.5 23.9 27.4 28.7 18.8 29.4 10.1 24.6 28.2 15.7 18.3 14.1 29.3 8.7 11.6 30.2 21.4 13.7
17.9 18.0 11.9 17.7 16.0 12.6 14.5 29.2 18.9 8.9 16.4 23.2 31.5 25.8 25.4 20.6 16.3 27.5 17.6 14.6 17.5 7.9 11.1 14.8 16.0 12.9 10.1 11.5 10.9 8.6 16.7 18.3 10.5 28.2 20.3 13.4 17.1 28.8
20.9 22.5 29.9 23.6 29.4 27.6 31.9 36.1 29.0 28.3 25.4 39.1 28.8 9.7 28.3 29.4 29.6 31.9 32.4 27.4 30.1 28.4 27.9 30.0 33.3 27.4 39.2 31.6 28.6 34.3 33.3 29.6 27.5 40.9 39.1 25.2 27.2 33.3
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Reference Bour G, Martel F, Goffin L, Bayle B, Gangloff J, Aprahamian M, Marescaux J, Egly JM. (2014). Design and development of a robotized system coupled to microct imaging for intratumoral drug evaluation in a hcc mouse model. PLoS One 9:e106675.
Start codon
Stop codon
ATG
TAA
ATA
TAG
ATG
TAA
ATG
TAA
ATG ATG ATG
TAA TAA TAG
ATA
TAG
ATG ATG
TAA T– –
ATA ATG
TAA TAA
ATG
AGA
Strand H H H H H H H L H H H L L L L L H L H H H H H H H H H H H H H H H L L H H L
Ling Q, Shi W, Huang C, Zheng J, Cheng Q, Yu K, Chen S, et al. (2014). Epigenetic silencing of dual oxidase 1 by promoter hypermethylation in human hepatocellular carcinoma. Am J Cancer Res 4:508–17. Yu SJ, Kim YJ. (2014). Hepatitis B viral load affects prognosis of hepatocellular carcinoma. World J Gastroenterol 20: 12039–44. Zhu R, Meng ZL, Chen L, Chen W, Wang H, Hong YQ. (2014). Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus). Mitochondrial DNA. [Epub ahead of print].
