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Pleiotropic architectures of porcine immune and growth trait pairs revealed by a self-product-based transcriptome method

ABSTRACT: 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.

ORGANISM(S): Sus scrofa

PROVIDER: GSE207483 | GEO | 2022/12/29

REPOSITORIES: GEO

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Project description:During interphase, the inactive X chromosome (Xi) adopts an unusual 3D configuration known as the Barr body and is largely transcriptionally silent. Despite the importance of X inactivation, little is known about the 3D configuration of Xi and its relationship to gene silencing. We recently showed that in humans, Xi exhibits two distinctive structural features. First, Xi is partitioned into two huge intervals, called superdomains, such that pairs of loci in each superdomain show an enhanced contact frequency with one another. The boundary between the two superdomains lies near DXZ4, a macrosatellite repeat spanning ~300kb, whose Xi allele extensively binds the protein CTCF. Second, Xi exhibits extremely large loops, up to 77Mb long, called superloops. DXZ4 lies at the anchor of several superloops. Here, we use 3D mapping to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across mammals. We develop a novel variant of our in situ Hi-C protocol, dubbed COLA (COncatemer Ligation Assay) to probe the higher order structures formed by the superloops. In COLA, in situ proximity ligation of multiple extremely short fragments produced by the enzyme CviJI is used to efficiently map simultaneous proximity among three or more loci. Using data from Hi-C and COLA, we demonstrate that DXZ4 and other superloop anchors tend to co-locate simultaneously within the same cells, a result that is confirmed by 3D-FISH. Finally, we examine the effects of deleting DXZ4 from Xi in human cells. Using in situ Hi-C, microscopy, and RNA-FISH, we show that superdomains and superloops disappear; that Xi frequently dissociates into multiple separate structures; and that transcriptional silencing on Xi is compromised. Deletion of DXZ4 from the active X chromosome (Xa) has no such effect. Thus, DXZ4 is essential for proper folding and silencing of Xi. Hi-C protocol was used on wildtype and DXZ4-deleted cells to examine the structure of Xi. A novel variant of our in situ Hi-C protocol, dubbed COLA (COncatemer Ligation Assay), was developed to probe the higher order structures formed by the superloops. This series also includes RNA-seq data on Retinal Pigmented Epithelial Cells (hTERT-RPE1). At the time of submission, processed data were available only for the RNA-seq samples. Submitter states that processed data files for HiC samples will be added to this series in the future.

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Pleiotropic architectures of porcine immune and growth trait pairs revealed by a self-product-based transcriptome method

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