http://informahealthcare.com/mdn ISSN: 1940-1736 (print), 1940-1744 (electronic) Mitochondrial DNA, Early Online: 1–2 ! 2014 Informa UK Ltd. DOI: 10.3109/19401736.2014.987246
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the hepatocellular carcinoma model inbred Sprague–Dawley strain Sheng-Hang Zhang1*, Dong-Liang Li2*, Zhi-Qiang Zhang2, Xia Zhang2, and Li-Rong Cai2 Clinical Laboratory, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, Fuzhou, China and 2Department of Hepatobiliary Medicine, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, Fuzhou, China
Mitochondrial DNA Downloaded from informahealthcare.com by Universitat de Girona on 03/04/15 For personal use only.
1
Abstract
Keywords
In the present work we undertook the complete mitochondrial genome sequencing of an important hepatocellular carcinoma model inbred Sprague–Dawley strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one non-coding control region (D-loop region). The mutation events were also reported.
Genome, hepatocellular carcinoma, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In prostate cancer research, animal models have allowed the study of hepatocellular carcinoma (HCC) disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of HCC disease and the effects of drug intervention (Liu et al., 2014). HCC is among the oncological diseases with high prevalence, increased incidence and usually poor prognosis. At the early stage, surgical resection, liver transplantation and percutaneous radio-frequency are potentially curative treatments. HCC is the fifth most common cancer and the third cause of cancer-related mortality worldwide. More
History Received 2 November 2014 Accepted 10 November 2014 Published online 27 November 2014
than 600,000 people die from HCC each year. Although several major risk factors of HCC have been shown to contribute to hepatocarcinogenesis, the etiology is still unclear. Chronic inflammation developing through the action of various inflammatory mediators has been recently identified as a cofactor in carcinogenesis (Alifakioti et al., 2014; Hu et al., 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 (Lu & Gan, 2014).
Table 1. Genes encoded by this mitochondrial genome. Position Gene
From Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln tRNAMet ND2 tRNATrp tRNAAla tRNAAsn OL
362 432 1388 1455 3025 3102 4058 4124 4198 4267 5309 5377 5447 5520
Base composition (%) To 429 1386 1454 3024 3099 4058 4126 4195 4266 5310 5375 5445 5519 5550
Size (bp)
A
C
G
T
67 955 67 1570 75 957 69 72 69 1044 67 69 73 31
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 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
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
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
Start codon
Stop codon
ATG
TAA
ATA
TAG
Strand H H H H H H H L H H H L L L (continued )
*These authors contributed equally to this work. Correspondence: Dong-liang Li, Department of Hepatobiliary Medicine, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, No. 156 Xi Er Huan Road, Fujian 350025, China. E-mail: [email protected]
2
S.-H. Zhang et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Continued.
Position Gene
Mitochondrial DNA Downloaded from informahealthcare.com by Universitat de Girona on 03/04/15 For personal use only.
Cys
tRNA 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
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
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 68 1545 69 68 684 63 201 681 804 69 357 69 297 1378 70 60 71 1821 528 69 1140 70 66
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
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
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
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
Here, we reported complete mitochondrial genome sequence of an HCC inbred Sprague–Dawley rat model. Total DNA was extracted from the HCC tissue of a female individual that harboring a serious HCC. 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 is 16,308 bp long including 13 proteincoding genes, two rRNA genes, 22 tRNA genes and one control region. The total length of the protein-coding gene sequences is 11,437 bp. Most protein-coding genes initiate with ATG except for ND2, ND3 and ND5 which begin with ATA. Eight proteincoding genes terminate with TAA whereas the ND2, ND3 and COX3 genes terminates with TAG and the CytB gene terminates 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 vary 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 noncoding RNA sequences, and 45.8% were synonymous variants.
Start codon
Stop codon
ATG
TAA
ATG
TAA
ATG ATG ATG
TAA TAA TAG
ATA
TAG
ATG ATG
TAA T– –
ATA ATG
TAA TAA
ATG
AGA
Strand L L H L H H H H H H H H H H H H H H H L L H H L
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. This study is supported by: the Natural Science Foundation of Fujian Province, No. 2012J01399.
References Alifakioti D, Daccord C, Lachenal Y, Fitting JW. (2014). Acute eosinophilic and neutrophilic pneumonia following transarterial chemoembolization with drug-eluting beads loaded with doxorubicin for hepatocellular carcinoma: A case report. Respiration 88:426–9. Hu Q, Lou GG, Liu YC, Qian L, Lv BD. (2014). The tumor necrosis factor-alpha-308 and -238 polymorphisms and risk of hepatocellular carcinoma for Asian populations: A meta-analysis. Curr Ther Res Clin Exp 76:70–5. Liu N, Yang J, Huang Y, Chen B, Chen W, Li J. (2014). Vascular endothelial growth factor accelerates establishment of a model of hepatic metastasis in walker-256 tumor-bearing rats. Am J Med Sci. [Epub ahead of print]. doi: 10.1097/maj.0000000000000359. Lu XY, Gan CB. (2014). Mitochondrial genome of a melanoma disease model rat strain (Muridae; Rattus). Mitochondrial DNA. [Epub ahead of print]. doi: 10.3109/19401736.2014.947594.
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the hepatocellular carcinoma model inbred Sprague–Dawley strain Sheng-Hang Zhang1*, Dong-Liang Li2*, Zhi-Qiang Zhang2, Xia Zhang2, and Li-Rong Cai2 Clinical Laboratory, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, Fuzhou, China and 2Department of Hepatobiliary Medicine, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, Fuzhou, China
Mitochondrial DNA Downloaded from informahealthcare.com by Universitat de Girona on 03/04/15 For personal use only.
1
Abstract
Keywords
In the present work we undertook the complete mitochondrial genome sequencing of an important hepatocellular carcinoma model inbred Sprague–Dawley strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one non-coding control region (D-loop region). The mutation events were also reported.
Genome, hepatocellular carcinoma, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In prostate cancer research, animal models have allowed the study of hepatocellular carcinoma (HCC) disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of HCC disease and the effects of drug intervention (Liu et al., 2014). HCC is among the oncological diseases with high prevalence, increased incidence and usually poor prognosis. At the early stage, surgical resection, liver transplantation and percutaneous radio-frequency are potentially curative treatments. HCC is the fifth most common cancer and the third cause of cancer-related mortality worldwide. More
History Received 2 November 2014 Accepted 10 November 2014 Published online 27 November 2014
than 600,000 people die from HCC each year. Although several major risk factors of HCC have been shown to contribute to hepatocarcinogenesis, the etiology is still unclear. Chronic inflammation developing through the action of various inflammatory mediators has been recently identified as a cofactor in carcinogenesis (Alifakioti et al., 2014; Hu et al., 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 (Lu & Gan, 2014).
Table 1. Genes encoded by this mitochondrial genome. Position Gene
From Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln tRNAMet ND2 tRNATrp tRNAAla tRNAAsn OL
362 432 1388 1455 3025 3102 4058 4124 4198 4267 5309 5377 5447 5520
Base composition (%) To 429 1386 1454 3024 3099 4058 4126 4195 4266 5310 5375 5445 5519 5550
Size (bp)
A
C
G
T
67 955 67 1570 75 957 69 72 69 1044 67 69 73 31
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 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
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
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
Start codon
Stop codon
ATG
TAA
ATA
TAG
Strand H H H H H H H L H H H L L L (continued )
*These authors contributed equally to this work. Correspondence: Dong-liang Li, Department of Hepatobiliary Medicine, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, No. 156 Xi Er Huan Road, Fujian 350025, China. E-mail: [email protected]
2
S.-H. Zhang et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Continued.
Position Gene
Mitochondrial DNA Downloaded from informahealthcare.com by Universitat de Girona on 03/04/15 For personal use only.
Cys
tRNA 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
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
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 68 1545 69 68 684 63 201 681 804 69 357 69 297 1378 70 60 71 1821 528 69 1140 70 66
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
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
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
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
Here, we reported complete mitochondrial genome sequence of an HCC inbred Sprague–Dawley rat model. Total DNA was extracted from the HCC tissue of a female individual that harboring a serious HCC. 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 is 16,308 bp long including 13 proteincoding genes, two rRNA genes, 22 tRNA genes and one control region. The total length of the protein-coding gene sequences is 11,437 bp. Most protein-coding genes initiate with ATG except for ND2, ND3 and ND5 which begin with ATA. Eight proteincoding genes terminate with TAA whereas the ND2, ND3 and COX3 genes terminates with TAG and the CytB gene terminates 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 vary 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 noncoding RNA sequences, and 45.8% were synonymous variants.
Start codon
Stop codon
ATG
TAA
ATG
TAA
ATG ATG ATG
TAA TAA TAG
ATA
TAG
ATG ATG
TAA T– –
ATA ATG
TAA TAA
ATG
AGA
Strand L L H L H H H H H H H H H H H H H H H L L H H L
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. This study is supported by: the Natural Science Foundation of Fujian Province, No. 2012J01399.
References Alifakioti D, Daccord C, Lachenal Y, Fitting JW. (2014). Acute eosinophilic and neutrophilic pneumonia following transarterial chemoembolization with drug-eluting beads loaded with doxorubicin for hepatocellular carcinoma: A case report. Respiration 88:426–9. Hu Q, Lou GG, Liu YC, Qian L, Lv BD. (2014). The tumor necrosis factor-alpha-308 and -238 polymorphisms and risk of hepatocellular carcinoma for Asian populations: A meta-analysis. Curr Ther Res Clin Exp 76:70–5. Liu N, Yang J, Huang Y, Chen B, Chen W, Li J. (2014). Vascular endothelial growth factor accelerates establishment of a model of hepatic metastasis in walker-256 tumor-bearing rats. Am J Med Sci. [Epub ahead of print]. doi: 10.1097/maj.0000000000000359. Lu XY, Gan CB. (2014). Mitochondrial genome of a melanoma disease model rat strain (Muridae; Rattus). Mitochondrial DNA. [Epub ahead of print]. doi: 10.3109/19401736.2014.947594.
