| Immunity,growth and reproduction are all important quantitative traits in pig breeding.It is one of the most important tasks to dissect the genetic mechanism of these traits.With the development of whole-genome molecular markers detection technologies,quantitative trait loci(QTL)mapping or genome-wide association studies(GWAS)have been widely used to study the molecular genetic mechanism of these traits.More importantly,these traits are correlated and interacted with each other.For instance,many immune factors have been proved to play roles in growth and reproductive processes;energy is preferentially allocated to essential immune activities rather than growth and reproduction,which results in the trading-off relationship among them.In addition,we found that the imported pigs from developed countries performed worse and worse on productive traits in Chinese pig farms with poorer hygiene condition and more complicated vaccination procedure,which might be due to the influence of immunity on other traits.Unfortunately,it has been very rare to genetically study the correlations between immunity and growth,and between immunity and reproduction.Meanwhile,it is unclear how the change of vaccination procedure or environmental hygiene condition influences the productive traits like growth and reproduction.In addition,if this environmental differences persist,whether it will cause the variation of genetic architecture of a population is also worth studying.It will be significant for animal breading,human health,scientific use of vaccine and improvement of environment to study these problems.Therefore,we have performed the following 6 studies and got some results.(1)The genetic background of the correlations among traits is the pervasive pleiotropy along the genome,which can be classified as biological pleiotropy(causal variants of different traits fall into the same gene),spurious pleiotropy(causal variants of different traits fall into different genes which are in linkage disequilibrium),mediated pleiotropy(causal variants of different traits fall into different genes which interact with each other).Therefore,based on pig QTL database,we firstly annotated QTL overlapping intervals between immunity and growth,and between immunity and reproduction.As a result,we identified 482 biological pleiotropic genes,8 spurious pleiotropic linkage blocks and 29 mediated pleiotropic pathways between immunity and growth,and the corresponding numbers between immunity and reproduction were 101,4 and 45.These results also indicated that biological pleiotropy plays important role in the correlation between immunity and growth,while the correlation between immunity and reproduction mainly depends on the mediated pleiotropy.(2)The genetic correlation coefficients,between immunity and growth,and between immunity and reproduction were calculated based on the summary statistics of human genome-wide association studies(GWAS).The and cause-and-effect relationship between these traits were also studied by Mendelian randomization.As a result,there exists statistically significant correlations between immunity and growth,and between immunity and reproduction,and the correlation between immunity and growth was negative.Human height trait was negatively influenced by three traits of immune cells.In addition,the homologous pig genes were identified using the results of human GWAS to supplement pleiotropic genes identified by QTL database.At last,we identified 639 biological pleiotropic genes,29 spurious pleiotropic genes and 505 mediated pleiotropic genes between immunity and growth,and the corresponding numbers between immunity and reproduction were 127,14 and 404,which lay a good foundation for further steps.(3)We compared two sets of estimated breeding values(EBV)of four growth traits of a single Duroc pig population.One set of EBV was calculated using the information of their relatives in China,and the other set was calculated based on the information of their relatives in USA.Negative correlation coefficient(-0.21,P=0.01)was observed for the trait of days to 115 kg between the two sets of EBV,indicating the re-ranking of animals.This result illustrated that the environmental effect significantly influenced on the genetic background of growth,and the existence of gene-environment interaction.Considering that vaccination procedure in Chinese pig farm is much more complicated than that in American pig farm,this result might be due to that environmental difference changed genetic background of immunity,which further influenced the growth traits by pleiotropy.(4)In order to verify the hypothesis above,cattle were taken as model animals of pigs in this step.We measured four female fertility traits of Danish Holstein cattle in conventional herds with complicated vaccination procedure and organic herds with simple vaccination procedure,and part of animals were genotyped using 50 K single nucleotide polymorphism(SNP)chip to study the genetic mechanism of fertility traits influenced by different herds environments.As a result,higher fertility could be observed for cattle in organic herds,and genetic background of two fertility traits were influenced by environment significantly.A total of 110 genes were identified to be affected by environment using GWAS,among which 7 genes were found in mediated pleiotropic gene sets between immunity and reproduction,which reached the significant level of enrichment(P=0.0007).These results validated our previous hypothesis that environment can affect genetic pleiotropy of immune traits,which will further influence other traits.(5)We performed a genomic comparison between two Duroc populations which originated from the same population using 76895 genome-wide SNPs.One Duroc population(D05)was in Chinese environment and the other one(D13)was in American environment.The results of principal component analysis and population structure analysis indicated that significant divergence had already appeared in the two populations as a result of different selection pressures within short time,though.Using selection signal detection method based on population differentiation,we identified significant selection signals between D05 and D13,which were related to immunity(PSMA)and meat quality(PPP2R5A and PGM1).In addition,on the immunity-related signal,the genetic distance(0.46)between D05 and Chinese Taihu pigs,which have high immunity and adaptability to Chinese environment,was shorter than that between D13 and Chinese Taihu.These results indicated that in order to adapt to the environmental change,population genetic structure can be influenced even in a short time.(6)We detected positive selection signals between Chinese indigenous pigs and western pig breeds based on population differentiation using 129882 genome-wide SNPs.The most significant signal was in a pleiotropic gene,IGF1 R,related to immunity,growth and reproduction,and 11 out of a total of 182 candidate genes were from pleiotropic gene set between immunity and growth,which nearly reached the significant level of enrichment(P=0.068),and 8 was included in mediated pleiotropic genes between immunity and reproduction,which reached significant level of enrichment(P=0.048).Then we detected runs of homozygosity(ROH)regions along genomes of Chinese and western pig populations,respectively.The results showed that Chinese pigs had more autosomes covered by long ROH(27.2%)than western pigs(17.3%),while western pigs had more autosomes covered by short ROH(82.6%)than Chinese pigs(72.8%).Among 173 genes involved in high frequent long ROH regions in Chinese pigs,14 were from biological pleiotropic gene set between immunity and growth(P=0.015),and 5 were from biological pleiotropic gene set between immunity and reproduction(P=0.018),both of which reached significant level of enrichment.These results indicated that different selection pressures of Chinese and western environments can affect pleiotropy and further caused different germplasms of Chinese and western pigs,and also verified the co-evolution of immune,growth and reproductive traits during the adaption to the environment.In summary,this thesis dissected thoroughly the genetic background of correlations between immune and growth traits,and between immune and reproductive traits in pigs.This helped us to study the mechanism of influences of environment on genetic background of immunity,which further caused the variation of growth and reproductive traits.These results helped to understand the correlations among different traits,and arevery theoretically instructive for gene editing,scientific import of pigs,pig breeding,and development of vaccination and pharmacy. |
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