Pleiotropic architectures of porcine immune and growth trait pairs revealed by a self-product-based transcriptome method
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PROVIDER: PRJNA855903 | ENA |
REPOSITORIES: ENA
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Project description:Pleiotropy is an important biological phenomenon with complicated genetic architectures for multiple traits. To date, pleiotropy was mainly identified by multi-trait GWAS, but GWAS method has its disadvantages, and new developments for pleiotropy detection methods are needed. Here we defined a novel metric, self-product, and based on it, we developed a transcriptome method to identify candidate pleiotropic genes and revealed the genetic architectures of immune and growth trait pairs in pigs. In statistics, the well-known covariance is used to quantify the co-variation between two variables. Suppose that X and Y represent two traits with individual records of xi and yi and corresponding means of μx and μy. We defined the individual-level product (xi − μx)(yi − μy) as self-product. Obviously, self-product is an individual-level measurement for the co-variation between two traits of the ith individual, and the covariance Cov(X , Y) is the mean of the self-product (xi − μx)(yi − μy). The self-product-based transcriptome method was tested using immune and growth trait pairs in pigs.We identify candidate pleiotropic genes using the Affymetrix Porcine Genechip. Result:Comparative transcriptome analyses identified dozens of candidate pleiotropic genes related to 8 trait pairs from two tails of self-product distribution. GO enrichment analysis indicated that most of identified pleiotropic genes were involved in both immune- and growth-related biological processes. We established pleiotropic genes interaction network to exhibit core genes shared by 8 trait pairs, of which CCL5 and IL-10 genes were hub genes. Genetic association analyses showed that SmaI-polymorphisms of CCL5 and IL-10 genes had significant associations with phenotypic co-variations of multiple trait pairs, indicating that the variants in pleiotropic genes were also pleiotropic variants. Conclusions:The validity of our proposed method was preliminarily verified, and our findings provide new insights into the genetic basis of pleiotropic architectures of immune and growth trait pairs in pigs.
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Project description:There is currently much debate about how much the genetic heritability of complex traits is due to very rare alleles. This issue is important because it determines sampling strategies for genetic association studies. Several recent theoretical papers based on a pleiotropic model for trait evolution suggest that it is possible that a large proportion of the genetic variance could be explained by rare alleles. This model assumes that mutations with a large effect on fitness also tend to have large positive or negative effects on phenotypic traits. We show that conclusions based on standard diffusion results are generally applicable to simulations of whole genomes with overlapping generations in a finite population, although the variance contribution of rare alleles is somewhat smaller than theoretical predictions. We show that under many scenarios the pleiotropic model predicts trait distributions that are unrealistically leptokurtic. We argue that this imposes a limit on the relationship between fitness and trait effects.
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