RESUMO
Mitochondrial DNA mutations play crucial roles in the pathogenesis and progression of human malignancies. Therefore, to determine whether maternal background or mitochondrial DNA somatic mutations were essential cofactors in the lung cancer of Chinese patients as well, the complete mitochondrial DNA displacement loop of the primary cancerous, matched para-cancerous normal and distant normal tissues for 79 Chinese patients with lung cancer were analyzed in this study. Our results indicated that the higher detected frequency of haplogroups prevalent in southern East Asia (53.16%; 42/79) versus those of northern East Asia in the studied population supported the southern East Asian characteristics of the Chinese lung cancer group. Further statistical analysis revealed that the haplogroups F* and G* contributed to the susceptibility to lung cancer in Chinese patients. In addition, by comparing sequences from different tissues of the same patients, a total of eight somatic mutations from six patients were detected. Combined with the fourteen somatic mutations identified in our previous study, the somatic mutation spectrum of the 79 Chinese patients with lung cancer was 25.32% (20/79). Our results suggest that mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Yunnan, Southwest China, and that somatic mitochondrial DNA mutations in the displacement loop can serve as potential biomarkers for clinical utility.
Assuntos
DNA Mitocondrial/genética , Predisposição Genética para Doença , Genoma Mitocondrial , Haplótipos , Neoplasias Pulmonares/genética , Mutação , Povo Asiático , Sequência de Bases , Feminino , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , FilogeniaRESUMO
The mitochondrion is a crucial intracellular organelle responsible for regulating cellular energy metabolism, producing free radicals, initiating and executing the apoptotic pathways. Previous studies have shown that somatic mutations in mitochondrial DNA are associated with various tumors, which may be involved during carcinogenesis and tumor progression. To examine the mutation pattern in cancer, 625 reported somatic mutations in the mitochondrial DNA genome were analyzed. We found that, except for deletions and insertions, most somatic mutations were point mutations, accounting for 89.44% of somatic mutations. Transition was the predominant form of somatic mutation in the entire mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which were homoplastic. Frequency statistics analysis of point mutations indicated that, except for 3 tRNA genes, the mutations were distributed on all resting genes and in the D-loop region, with the latter showing the highest frequency of somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA genes showed a relatively lower frequency of somatic point mutations. Nonsynonymous mutations and terminal amino acid changes were the primary point somatic mutations detected from 13 coding-region genes, which may cause mitochondrial dysfunction in cancer cells. We found that the somatic mutations may affect the mitochondrial DNA genome; the non-coding region should be examined to identify somatic mutations as potential diagnostic biomarkers for early detection of cancer.
Assuntos
Análise Mutacional de DNA , DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Mitocôndrias/genética , Sequência de Bases/genética , Humanos , Mutação/genéticaRESUMO
Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality throughout the world. The purpose of our study was to uncover biomarkers and explore its pathogenic mechanisms at the molecular level. The gene expression profiles of COPD samples and normal controls were downloaded from Gene Expression Omnibus. Matlab was used for data preprocessing and SAM4.0 was applied to determine the differentially expressed genes (DEGs). Furthermore, a protein-protein interaction (PPI) network was constructed by mapping the DEGs into PPI data, and functional analysis of the network was conducted with BiNGO. A total of 348 DEGs and 765 interactive genes were identified. The hub genes were mainly involved in metabolic processes and ribosome biogenesis. Several genes related to COPD in the PPI network were found, including CAMK1D, ALB, KIT, and DDX3Y. In conclusion, CAMK1D, ALB, KIT, and DDX3Y were chosen as candidate genes, which have the potential to be biomarkers or candidate target molecules to apply in clinical diagnosis and treatment of COPD.
Assuntos
Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas/genética , Doença Pulmonar Obstrutiva Crônica/genética , Transdução de Sinais/genética , Biomarcadores/metabolismo , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença/genética , Humanos , Antígenos de Histocompatibilidade Menor , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Albumina Sérica/genética , Albumina Sérica/metabolismo , Albumina Sérica HumanaRESUMO
The spotted babylon, Babylonia areolata, is one of the most extensively cultured marine mollusks in southeast Asia. Eight polymorphic microsatellite markers were developed for this species, from a microsatellite-enriched library. These markers, characterized in 32 individuals from a hatchery population, were polymorphic, with allele numbers ranging from 6 to 18 per locus, expected and observed heterozygosities ranging from 0.68 to 0.94 and 0.56 to 0.81, respectively. One locus (HUBA09) showed significant deviation from Hardy-Weinberg equilibrium, probably due to the presence of null alleles. These microsatellite loci should be useful for future population genetic studies and marker-assisted breeding in this species.
Assuntos
DNA/genética , Gastrópodes/genética , Repetições de Microssatélites , Alelos , Animais , Sudeste Asiático , Cruzamento , Primers do DNA/genética , Loci Gênicos , Biblioteca Genômica , Técnicas de Genotipagem , Heterozigoto , Polimorfismo Genético , Análise de Sequência de DNARESUMO
The abalone, Haliotis diversicolor, is one of the most important mariculture species in southern China. We developed 60 new polymorphic microsatellite markers for H. diversicolor and characterized them in 30 individuals from a cultured population in Sanya, China. All 60 markers were found to be polymorphic. The number of alleles ranged from two to nine per locus, with an average of 4.12/locus. The expected and observed heterozygosities ranged from 0.10 to 0.88 and from 0.07 to 0.87, respectively. Forty-four loci were in Hardy-Weinberg equilibrium. These 44 microsatellite markers should be useful for genome mapping and population genetic studies.