A color image encryption algorithm based on hyperchaotic map and DNA mutation

We devise a color image encryption scheme via combining hyperchaotic map,cross-plane operation and gene theory.First,the hyperchaotic map used in the encryption scheme is analyzed and studied.On the basis of the dynamics of hyperchaotic map,a color image encryption scheme is designed.At the end of the encryption process,a DNA mutation operation is used to increase the encoding images’randomness and to improve the encryption algorithm’s security.Finally,simulation experiments,performance analysis,and attack tests are performed to prove the effectiveness and security of the designed algorithm.This work provides the possibility of applying chaos theory and gene theory in image encryption.

Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

Alterations in oxidative phosphorylation resulting from mitochondriai dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA （mtDNA） mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

Mitochondrial DNA Mutations Associated with Aminoglycoside Ototoxicity

The mitochondrial 12S rRNA has been shown to be the hot spot for mutations associated with both aminoglycoside-induced and non-syndromic hearing loss. Of all the mutations, the homoplasmic A1555G and C1494T mutations at a highly conserved decoding region in the 12S rRNA have been associated with aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. The A1555G or C1494T mutation is expected to form novel 1494C-G1555 or 1494U-A1555 base-pair at the highly conserved A-site of 12S rRNA. These transitions make the secondary structure of this RNA more closely resemble the corresponding region of bacterial 16S rRNA. Thus, the new U-A or G-C pair in 12S rRNA created by the C1494T or A1555G transition facilitates the binding of aminoglycosides, thereby accounting for the fact that the exposure to aminoglycosides can induce or worsen hearing loss in individuals carrying these mutations. Furthermore, the growth defect and impairment of mitochondrial translation were observed in cell lines carrying the A1555G or C1494T mutation in the presence of high concentration of aminoglycosides. In addition, nuclear modifier genes and mitochondrial haplotypes modulate the phenotypic manifestation of the A1555G and C1494T mutations. These observations provide the direct genetic and biochemical evidences that the A1555G or C1494T mutation is a pathogenic mtDNA mutation associated with aminoglycoside-induced and nonsyndromic hearing loss. Therefore, these data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.

A Preliminary Study on DNA Mutation Induction of Maize Pollen Implanted by Low Energy N^+ Beam

The maize pollens were implanted with seven different doses of 30 keV N+ beam respectively, The genomic DNA polymorphism from treated pollens were analyzed with 104 primers by using RAPD respectively. The results showed that N^+ beam-induced mutation of maize pollens can result in the change of their DNA bases. The mutation is not properly random and its frequency increases with a rise in 30 keV N+ beam doses. It is conformed with A-G transformation, which is one of the most important factors in DNA bases induced by N+ beam.

Late-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with mitochondrial DNA 3243A>G mutation masquerading as autoimmune encephalitis:A case report

BACKGROUND Here,we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)syndrome,which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation.CASE SUMMARY A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations,symmetrical bitemporal lobe abnormalities,clinical and laboratory findings,and a lack of relevant prodromal history,which suggested diagnosis of autoimmune encephalitis.Further work-up,in conjunction with the patient’s medical history,family history,and lactate peak on brain lesions on magnetic resonance imaging,suggested a mitochondrial disorder.Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene,which led to a diagnosis of MELAS syndrome.CONCLUSION This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age,as the symptoms and signs are atypical for MELAS syndrome.

Sensitive DNA Mutation Detection at Physiological Temperature with Endonuclease IV by Inhibiting Its Side Activity

Endonuclease IV(Endo IV)has the side activity to cleave the apurinic/apyrimidinic site in the single-stranded DNA probe(AP-ssDNA),which adversely affects its performance in single-nucleotide variation(SNV)detection.In this work,we developed a simple strategy to inhibit Endo IV's side activity by introducing an assistant strand into the detection system.The assistant strand effectively inhibited the side-activity of Endo IV by conf ini ng the freedom of AP-ssDNA through rigid double-stranded DNA formati on,and the inhibition efficiency could reach 98%.About 20 times enhancement of the discrimination factor(DF)was obtained compared to the detection system without the assistant strand.After optimization,a mean DF value was calculated to be 738 for different mutation types,and the sample with 0.005%allele frequency was discriminated from the wild-type target.Another advantage of using an assists nt stra nd was that the SNV detection could be executed at physiological temperature without precise temperature optimization as in other Endo IV-based SNV detection system.Besides,EGFR T790M mutant in the synthesized and clinical samples was detected by our strategy.The results showed satisfactory sensitivity and accuracy by comparison with Sanger sequencing.Thus,this strategy has the potential to be applied in the field of precision medicine.

Remarkably different results between two studies from North America on genomic mutations and sensitivity to DNA demethylating agents for myelodysplastic syndromes

Sekeres et al. （1） conducted a multicenter randomized, controlled trial to compare whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates to azacitidine in the treatment of myelodysplastic syndromes （MDS）. In that trial, 224 patients with higher-risk MDS and 53 with chronic myelomonocytic leukemia （CMML） were enrolled and randomly assigned to the ＂azacitidine＂ group, ＂azacitidine plus lenalidomide＂ group or ＂azacitidine plus vorinostat＂ group. The researchers found that patients with MDS treated with azacitidine-based combinations had similar response rate to azacitidine monotherapy. Using genomic mutation analysis, they found that the overall response rate to azacitidine-based treatment was higher for patients with mutations in DNMT3A and lower for those with mutations in SRSF2. Whereas in another study, Welch et al. enrolled 26 patients with MDS and 90 with acute myeloid leukemia （AML） who were treated with decitabine, and they found that patients with TP53 mutations had a higher response rate, but not those with DNMT3A mutations （2）. We propose that this big discrepancy in the conclusions between the two studies might have been caused by the presence of many co-interacting factors, e.g. study aims, DNA demethylating agents, treatment protocols, and patient sources.

APC and K-ras gene mutation in aberrant crypt foci of human colon

AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .

Comparative analysis of dideoxy sequencing,the KRAS StripAssay and pyrosequencing for detection of KRAS mutation

AIM:To compare the differences between dideoxy sequencing/KRAS StripAssay/pyrosequencing for detection of KRAS mutation in Chinese colorectal cancer (CRC) patients.METHODS:Formalin-f ixed, paraff in-embedded (FFPE) samples with tumor cells ≥ 50% were collected from 100 Chinese CRC patients at Beijing Cancer Hospital. After the extraction of genome DNA from FFPE samples, fragments contained codons 12 and 13 of KRAS exon 2 were amplified by polymerase chain reaction and analyzed by dideoxy sequencing, the KRAS Strip Assay and pyrosequencing. In addition, the sensitivities of the 3 methods were compared on serial dilutions (contents of mutant DNA: 100%,50%,20%, 5%,10%, 5%,1%,0%) of A549 cell line DNA (carrying the codon 12 Gly>Ser mutation) into wild-type DNA (human normal intestinal mucosa). The results of dideoxy sequencing,the KRAS StripAssay and pyrosequencing were analyzed by Chromas Software, Collector forKRAS Strip Assay and the pyrosequencing PyroMarkTM Q24 system, respectively.RESULTS: Among 100 patients, KRAS mutations were identif ied in 34%, 37% and 37% of patients by dideoxy sequencing, the KRAS StripAssay and pyrosequencing, respectively. The sensitivity was highest with the KRAS Strip Assay (1%), followed by pyrosequencing (5%), and dideoxy sequencing was lowest (15%). Six different mutation types were found in this study with 3 main mutations Gly12 Asp (GGT>GAT), Gly12 Val (GGT>GTT) and Gly13 Asp (GGC>GAC). Thirty-three patients were identifi ed to have KRAS mutations by the 3 methods, and a total of 8 patients had conflicting results between 3 methods: 4 mutations not detected by dideoxy sequencing and the KRAS StripAssay were identified by pyrosequencing; 3 mutations not detected by dideoxy sequencing and pyrosequencing were identif ied by the KRAS StripAssay; and 1 mutation not detected by pyrosequencing was conf irmed by dideoxy sequencing and the KRAS StripAssay. Among these discordant results, the results identif ied by dideoxy sequencing were consistent either with the KRAS StripAssay or with pyrosequencing, which indicated that the accuracy of dideoxy sequencing was high. CONCLUSION: Taking a worldwide view of reports and our results,dideoxy sequencing remains the most popular method because of its low cost and high accuracy.

Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression

Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA(mtDNA).In the past decades,several types of somatic mtDNA alterations have been identified in gastric cancer.However,the role of these mtDNA alterations in gastric cancer progression remains unclear.In this review,we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer.The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed.We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers.The two primary mutation types(transition mutations and mononucleotide or dinucleotide repeat instability)imply potential causative factors.Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer.The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.

Polymorphism analysis of PARK2 gene mutations in Han Chinese patients with early-onset Parkinson's disease

The PARK2 gene is a common disease gene in Han Chinese patients with Parkinson＇s disease.The detection of mutations in the PARK2 gene remains low.To investigate the role PARK2 gene mutations play in the pathogenesis of Parkinson＇s disease,30 Han Chinese patients with early-onset Parkinson＇s disease and 38 normal controls were studied to determine the sequence changes of 1,4,6 and 7 exon sections.In the 30 patients with Parkinson＇s disease,a heterozygous intron mutation（nt 119,G→G/A）in exon 1 was detected in one case;a homozygous intron mutation（nt 526500,T→C）between intron 3 and exon 4 in fourteen cases was found;a heterozygous intron mutation（nt 526607,G→G/A）between intron 3 and exon 4 was observed in eight cases;an exon 6missense mutation（nt 754317,C→C/T;codon 193,CGG→CGG/TGG;aa 193,Arg→Arg/Trp）in three cases was seen;and an exon 7 missense mutation（nt 941943,C→A/C;codon 272,CTC→CTC/ATC;aa 272,Leu→Leu/lle）was found in one case.These changes were not found in the normal population.The results indicated that the PARK2 exons 6 and 7 mutations are possibly pathogenic mutations,along with the intron 3-exert 4 and exon 1 mutations.PARK2 gene mutations are possible factors leading to the onset of Parkinson＇s disease.

Sequencing of hepatitis C virus cDNA with polymerase chain reaction directed sequencing *

AIM To explore a rapid and easy sequencing method for hepatitis C virus (HCV) genome, and establish a new sequencing method in China. METHODS Polymerase Chain Reaction (PCR) was combined with DNA sequencing technique. PCR products were purified by agarose gel electrophoresis, polyacrylamide gel electrophoresis (PAGE), Polyethylene glycol (PEG) respectively. Then in the presence of a 5′ labeling PCR primer, purified PCR products were directly sequenced. By this method, HCV NS5b cDNA from two HCV infected individuals (HC 42 and HC 49) were sequenced.

Novel ATP7B gene mutations in Chinese Han patients with hepatolenticular degeneration

BACKGROUND： ATP7B gene exon 8 Arg778Leu and exon 12 Arg952Lys are gene mutation hot spots in Chinese Han patients with hepatolenticular degeneration, or Wilson＇s disease （WD）. However, the gene fragments are too short for detection and the mutation detection rate remains low. OBJECTIVE： To analyze DNA sequences of ATP7B gene exon 8-exon 9 and exon 10-exon 12 sections. DESIGN, TIME AND SE＇I-rlNG： A concurrent, non-randomized, controlled, genetic polymorphism study was performed at the Anhui Medical Genetics Center, Anhui, China from March to July in 2009. PARTICIPANTS： Fifty patients, who were admitted to the Department of Neurology at the First Affiliated Hospital of Anhui Traditional Chinese Medical College between March and July in 2009, were diagnosed with WD. The WD group comprised 32 males and 18 females, with an average age of （18.8 ± 8.3） years. WD was confirmed by clinical observation, as well as physical, imaging, and biochemical examinations, including testing for serum copper, ceruloplasmin, and copper oxidase. The control group comprised 20 normal subjects, who underwent physical examination at the First Affiliated Hospital of Anhui Traditional Chinese Medical College, and included 13 males and 7 females, with an average age of （27.9 ± 2.4） years. All subjects were Chinese Han population. METHODS： Genomic DNA was extracted from 50 WD patients and 20 normal controls. Polymerase chain reaction amplification of ATP7B gene exon 8-exon 9 （about 1 100 bp） and exon 10-exon 12 （about 850 bp） segments was performed. DNA exon-intron amplification products from all subjects were processed through direct bidirectional sequencing, and sequencing results were analyzed. MAIN OUTCOME MEASURES： Sequence changes of ATPTB gene exon 8-exon 9 and exon 10-exon 12 segments. RESULTS： In the 50 included WD patients, ATP7B gene intron 8 nt53592A → G with nt53671G→ A homozygous mutation was detected between exon 8-exon 9 in seven cases; exon 8 Arg778Leu mutations with Leu770Leu synonymous mutation was detected in four cases; exert 11 Gly790Arg heterozygous missense mutation between exon 10-exon 12 was found in four cases; exon 12 Arg952Lys heterozygous missense mutation was seen in 11 cases; and two additional cases were associated with exon 1211e929Val polymorphism. CONCLUSION： ATP7B gene intron 8 mutation is a possible pathogenic mutation that is associated with WD pathogenesis. The exon 11 mutation rate accounts for 8% of all WD patients, and the very few previously reported cases deserve further study.

DETECTION OF p53 GENE MUTATION IN PLASMA OF PATIENTS WITH GASTRIC CANCER

Objective: To investigated p53 gene mutation in plasma of gastric cancer patients. Methods: DNA extracted from plasma and matched tumor and tumor-adjacent non-cancerous tissues of 96 gastric cancer patients, and DNA from 20 healthy volunteers were studied. Exon 5, 6, 7, and 8 of p53 were amplified by Polymerase Chain Reaction (PCR). The mutation status was analyzed by denaturing high-performance liquid chromatography (DHPLC), followed by direct sequencing of cases with aberrant chromatographic patterns. Results: Heterozygous mutations of p53 gene were detected in 19.9% (19/96) of primary tumor tissues and 5.2% (5/96) of corresponding plasma. All p53 gene mutations detected in plasma DNA consisted with mutations in the matched primary tumor samples. Neither the tumor-adjacent gastric mucosa tissues nor control plasma from healthy volunteers showed p53 gene mutation. No correlation was found between p53 mutation status and clinicopathological features of gastric cancer patients. Conclusion: p53 gene mutation in plasma can be detected in tissues and plasma of gastric cancer patients, which could be applied in screening and surveillance of this disease.

Comprehensive cross cancer analyses reveal mutational signature cancer specificity

Mutational signatures refer to distinct patterns of DNA mutations that occur in a specific context or under certain conditions.It is a powerful tool to describe cancer etiology.We conducted a study to show cancer heterogeneity and cancer specificity from the aspect of mutational signatures through collinearity analysis and machine learning techniques.Through thorough training and independent validation,our results show that while the majority of the mutational signatures are distinct,similarities between certain mutational signature pairs can be observed through both mutation patterns and mutational signature abundance.The observation can potentially assist to determine the etiology of yet elusive mutational signatures.Further analysis using machine learning approaches demonstrated moderate mutational signature cancer specificity.Skin cancer among all cancer types demonstrated the strongest mutational signature specificity.

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

AIM： To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer （HNPCC） families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands. METHODS： Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography （DHPLC） were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles. RESULTS： One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms （77.9%） were diagnosed as colorectal cancer, with an average age of onset at 48.57 ±29.00 years. Gastric cancer was the most common extracolonic cancer （10.3%） in these families. Twenty-three different sequence variations in hMLHI and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic. CONCLUSION： Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.

A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage

Background： Cardiovascular diseases, including dilated cardiomyopathy （DCM） and hypertension, are the leading cause of death worldwide.The role of mitochondrial DNA （mtDNA） in the pathogenesis of these diseases has not been completely clarified.In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage.Methods： Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed.We divided all the family members into case （7 maternal members） and control group （7 nonmaternal members） for comparison.Clinical evaluations and sequence analysis ofmtDNA were obtained from all participants.Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations.Results： The majority of the family members presented with a maternal inheritance of hypertension and DCM.Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations.Among the mutations identified, there was only one significant mutation： A8701G （P =0.005）, which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives.There was no clear evidence for any synergistic effects between A8701G and other mutations.Conclusions： A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conj unction with genetic disorders caused by consanguineous marriage.

Point mutations of muscle mitochondrial DNA from patients with mitochondrial encephalomyopathies

Objective To study the relation between point mutations at nt3243 and nt8344 of muscle mitochondrial DNA from patients with mitochondrial encephalomyopathies and phenotypes. Methods DNA was extracted from muscle specimens from 5 patients with mitochondrial encephalomyopathies and amplified by PCR method, using corresponding oligonucleotide primers. DNA fragments were digested with restriction enzymes BglⅠ and ApaⅠ, then the digested DNA fragments were analyzed with an electrophoresis method.Results The point mutation at nt3243 of mtDNA was found in 2 patients, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and another with myoclonic epilepsy with ragged red fibers (MERRF). The point mutation at nt8344 was found in 2 patients with MERRF, including the one with point mutation at nt3243.Conclusion The point mutation of DNA at nt3243 correlated with MELAS and nt8344 correlated with MERRF. In addition, the detection of point mutations at both nt3243 and nt8344 in a patient with MERRF shows the association of mutation with diversity in clinical manifestations of mitochondrial encephalomyopathies.

Promoter methylation status of hMLH1,MGMT,and CDKN2A/p16 in colorectal adenomas

AIM:To investigate aberrant DNA methylation of CpG islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma(tu-bular or villous/tubulovillous)patients,and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1(hMLH1),Cyclin-dependent kinase inhibitor 2A(CDKN2A/p16),and O-6-methylguanine DNA methyltransferase(MGMT),as well as their rela- tion to MSI. RESULTS:The frequency of promoter methylation for each locus increased in the sequence healthy tissue/adenoma/carcinoma.MGMT showed the highest frequency in each group.MGMT and CDKN2A/p16 presented a statistically significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas(tubular vs tubullovillous and villous adenomas).All patients with tubulovillous/villous adenomas,as well as all colorectal cancer patients,showed promoter methylation in at least one of the examined loci.These findings suggest a potentially crucial role for methylation in the polyp/adenoma to cancer progres- sion in colorectal carcinogenesis.MSI and methylation seem to be interdependent,as simultaneous hMLH1, CDKN2A/p16,and MGMT promoter methylation was present in 8/9 colorectal cancer patients showing the MSI phenotype. CONCLUSION:Methylation analysis of hMLH1,CD- KN2A/p16,and MGMT revealed specific methylation profiles for tubular adenomas,tubulovillous/villous adenomas,and colorectal cancers,supporting the use of these alterations in assessment of colorectal tumorigenesis.

Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes

Background Recent studies have indicated that many mutations in mitochondrial (mt)DNA NDI gene region are related to diabetes mellitus. In this study we explored the relationship between various mtDNA ND1 gene mutations and type 2 diabetes mellitus (DM) among Chinese. Methods Using PCR restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing, 4 spots of mtDNA (nt3243, nt3316, nt3394, nt3426) were screened in 478 diabetics and 430 non-diabetic subjects.Results In diabetic group, there were 13 carriers (2.72%)of 3316 G→A mutation,12 (2.51%) of 3394 T→C mutation and 2 (0.42%) of 3426A→G mutation. In controls, only 3394 T→C mutation was observed in 2 subjects (0.47%). There was significant difference in the frequency of 3316 and 3394 mutation between two groups (P<0.05, respectively). More subjects with mitochondrial DNA ND1 gene mutations had DM family history and greater tendency of maternal inheritance when compared to those patients without mutation in diabetic group(P<0.01). A 3426 mutation diabetic pedigree was studied, and we found 12 maternal members in the family had the same mutation. Conclusion mtDNA ND1 gene mutations at nt3316 (G→A), nt3394 (T→C) and 3426 (A→G) might contribute to the pathogenesis of DM with other genetic factors and environment factors.