The Close Association Of Complicated Disease Susceptibility And Genetic Variation

Most complex traits are determined by both genetic and environmental factors. And genetic factors, can be divided into monogenic disease and polygenic disease. However, whether monogenic diseases or polygenic diseases, is focused on the function of major genes. Under the same environment, even if the main effect genes have no significant difference, different biological individuals still have different disease susceptibility, the individual difference of SNP is one of the causes of individual differences. C. elegans, as a kind of widely used model organism, only has innate immune ability. Upon pathogen infection, it can recognize a conservative inherent pattern, the so called Pathogen Associated Molecular Pattern(PAMP).Objective:Our research is to learn these function of the tiny effect SNP, so as to explore whethr the less MAC individuals have stronger on the evolution of conservative inherent immunityMethod:We calculated the minor allele contents (MAC) of recombinant inbred advanced intercross (RIAILs) of worms, which were produced by tinterbreeding between two Caenorhabditis elegans strains, and determined the MAC of each RIAILs by sequence analysis, we also shown that proteins involved in innate immunity are more conserved than those involved in the adaptive immune system. To investigate whether individual worms with lower MAC may have stronger innate immunity, we used the pathogen Pseudomonas aeruginosa14to infect different RIL strains and measured their life long age.Results:We found a negative correlation between life expectancy and MAC (R2=0.41, p<0.005).Conclusion:The results suggest that innate immunity is inversely proportional to the level of genetic variation. The degeneration of dopamine neurons is the pathological feature of Parkinson’s disease. One of the common agricultural herbicide, paraquat,has strong oxidiazation activity. It can increase intracellular reactive oxygen content, generate cytotoxic effect, and cause damage to dopamine neurons. It is one of the suspected pathogenicity factors of Parkinson’s disease. There is great variation in the risk of developing Parkinson’s disease among individuals of a populaiton.Objective:In order to better understand the fuction of paraquat and further understand of the relevant genetic mechanism at the same time.Method:We used recombinant inbred lines of nematodes to test the mortality, reactive oxygen content under50mm/L paraquat concentration, and brood size under200um/L paraquat concentration. We further identified several candidate genes involved in mortality and reproduction, including nhr-116, dct-16, and C18E9.5. We used RNAi to knock down these genes in wild type nematodes CB4856and N2Result:The results show that strains of high MAC has lower reproductive fitness and higher fatality rate, and lower reactive oxygen content(P<0.05).. RNA interference results showed that nhr-116RNAi incresed fatality rate, dct-16RNAi and C18E9.5RNAi decreased reproductive fitness (P<0.05).Conclusion:These results indicate that paraquat may affect worms of high MAC, and has implications for understanding the role of MAC or genetic diversity in the action of paraquat.