| Purpose:Research points that in the oldest old generally keep energy metabolism, indicates that mitochondria is an vital part of the cell/tissue to produce energy and play an significant role in human longevity. Studies have pointed out that some mutations could be beneficial to longevity by slowing down the function of the electron transport chain, reducing free radical production. We evaluated mitochondrial genome data as the main research object, using the second generation of high-throughput sequencing technologies (NGS) to. We sequenced the entire mitochondrial DNA from 34 individuals and examined aging-relatd variations in the Hainan population. Genetic analysis of mtDNA mutation and the relationship between the individual life, in order to further explore longevity genes and signaling pathways.Methods:In this study, we assessed sequence data by comparing two groups of whole SNP frequencies,individual SNP frequencies, the effect of SNPs, SNP accumulation in certain mtDNA regions. The mutation results in Burrows Wheeler Aligner (BWA) than to the human genome; Use GATK software for SNPS and InDel mutation detection, and associated the result of the variation with ANNOVAR software multiple databases (such as dbSNP,1000 g, ESP6500, etc.).Results:(1) Choose Hainan region,17 female cases that over 100-year-old age (age 100+2). All of centenarians are illiterate (100.0%),13 cases are agriculture, forestry and fishing workers(76.5%),15 cases(88.2%) are widowed, smoking in 17 cases (100.0%,1 case had given up smoking), drinking in 0 cases(0%), drinking tea in 5 cases (29.4%), one stool/1?2d of 17 cases (100.0%). age> 85 in 2 cases (11.7%), age< 85 in 11 cases (64.7%), can't prove that in 4 cases (23.5%).No important diseases (heart, lung and brain (Alzheimer's) 17 cases (100%).(2) All mtDNA sequence data were compared to reference sequence(rCRS). Sequencing of 16.596 mtDNA bases yielded a total of 355different single nucleotide variations at 794 positions in the centenarians and control groups. Most of the detected polymorphisms were transitions(93.1% for centenarians and 81.7% for controls),while transversions?insertions or deletions were less common.(3) Investigation on the distribution of SNP revealed considerable variability between groups.(4) 11 mutations would be found in the experimental group, the all experiment sample on these sites mutation;(5) Nine mutation was found in the experimental group, all of the experimental sample mutations in these genes;(6) Analysis of the detected SNPs revealed that the D-loop mutant were significantly associated with longevity (P=0.021); Frameshift mutant were significantly negative associated with longevity(P=0.0000);(7) Mitochondria integrity found no exception;(8) Found three mutations (310.3105.4048) significant differences between the experimental group and control group (p-value are:0.00005911,0.000000000857, 0.01669);(9) Found four genes or area (RNR1 RNR2, "RNR1, TRNF", "TRNP; CYTB, TRNT") there were significant differences between the experimental group and the control group.Conclusion:Our findings support a role formitochondrial genome variations and the functionality of oxidative phosphorylation in longevity. |
PDF Full Text Request