Sex Differences in Correlation with Gene Expression Levels between <i>Ifi200</i> Family Genes and Four Sets of Immune Disease-Relevant Genes

Cao, Yukun; Wang, Lishi; Wang, Cong-Yi; Ye, Jicheng; Wang, Ying; Li, Tiantian; Garcı́a-Godoy, Franklin; Sun, Dianjun; Gu, Weikuan; Postlethwaite, Arnold E.

doi:10.1155/2018/1290814

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…Ifi205 binds DNA in response to interferon signaling, which activates the immune system ( Albrecht et al 2005 ). Significant sex differences have been reported in mice, in which females have higher total Ifi205 expression levels than males ( Cao et al 2018 ). Growth arrest specific 1 ( Gas1 ) had significant diet and sex effects in LIV, reflected in strong SM/J biases in the three low fat diet-related (LF, LM, L), female, and “All” contexts.…”

Section: Resultsmentioning

confidence: 99%

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

et al. 2022

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Allele-specific expression (ASE) is a phenomenon where one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final allelic composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific gene regulation, but how they contribute to this crosstalk remains understudied. Here, we explored how allelic genotype, parent-of-origin, tissue type, sex, and dietary fat simultaneously influence ASE biases in a F1 reciprocal cross mouse model. Male and female mice from a F1 reciprocal cross of the LG/J and SM/J strains were fed a high fat or low fat diet. We harnessed strain-specific variants to distinguish between two classes of ASE: parent-of-origin dependent (unequal expression based on an allele's parental origin) and sequence dependent (unequal expression based on an allele's nucleotide identity). We present a comprehensive map of ASE patterns in 2,853 genes across three metabolically relevant tissues and nine environmental contexts. We found that both ASE classes are highly dependent on tissue type and environmental context. They vary across metabolic tissues, between males and females, and in response to dietary fat levels. We found 45 genes with inconsistent ASE biases that switched direction across tissues and/or contexts (e.g. SM/J biased in one cohort, LG/J biased in another). We also integrated ASE and QTL data from populations at various degrees of intercrossing the LG/J and SM/J strains. ASE genes in these tissues are often enriched in QTLs for metabolic and musculoskeletal traits, highlighting how this orthogonal approach can prioritize candidate genes for functional validation. Together, our results provide novel insights into how genetic, epigenetic, and environmental mechanisms govern allele-specific gene regulation, which is an essential step towards deciphering the genotype to phenotype map.

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Section: Resultsmentioning

confidence: 99%

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

et al. 2022

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“…Ifi205 binds DNA in response to interferon signaling, a cytokine family that activates the immune system. Significant sex differences have been reported in mouse Ifi205 expression levels, where females have higher total expression levels than males (Albrecht et al 2005; Cao et al 2018). Gas1 (growth arrest specific 1) had significant diet and sex effects in LIV, reflected in strong SM/J biases in the three low-fat fed diet-related (LF, LM, L), female, and “All” contexts.…”

Section: Resultsmentioning

confidence: 99%

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

Pierre

Macias-Velasco²,

Wayhart³

et al. 2021

Preprint

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Allele-specific expression (ASE) is a phenomenon where one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final allelic composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific gene regulation, but how they contribute to this crosstalk remains understudied. Here, we explored how allelic genotype, parent-of-origin, tissue type, sex, and dietary fat simultaneously influence ASE biases in a F1 reciprocal cross mouse model. Male and female mice from a F1 reciprocal cross of the LG/J and SM/J strains were fed a high-fat or low-fat diet. We harnessed strain-specific variants to distinguish between two classes of ASE: parent-of-origin dependent (unequal expression based on an allele's parental origin) and sequence dependent (unequal expression based on an allele's nucleotide identity). We present a comprehensive genome-wide map of ASE patterns across three metabolically-relevant tissues and nine environmental contexts. We find that both ASE classes are highly dependent on tissue type and environmental context. They vary across metabolic tissues, between males and females, and in response to dietary fat levels. Surprisingly, we also find several genes with inconsistent ASE biases that switched direction across tissues and/or contexts (e.g. SM/J biased in one cohort, LG/J biased in another). Together, our results provide novel insights into how genetic, epigenetic, and environmental mechanisms govern allele-specific gene regulation, which is an essential step towards deciphering the genotype to phenotype map.

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“…Transcriptomic expressions QTL (eQTL), which regulate the expression level of each of the four genes, are conducted using interval mapping platform at the GeneNetwork website. The procedure follows our previous publication and contains three major steps [ 28 ]. First, all possible probes of each of these four genes were identified from the kidney genome sets.…”

Section: Methodsmentioning

confidence: 99%

“…Animal models have been used to illustrate the molecular mechanisms of human diseases. The BXD strains of mouse model have become one of the preeminent genetic reference populations to understand the genetic variations and pathways of variety of diseases and phenotypes including sex difference [ 28 , 29 , 30 ]. Particularly regarding CKD, whole genome expression profiles from female and male of more than 70 BXD strains are currently available at the GeneNetwork ( (accessed between 4 December 2020–6 March 2021)).…”

Section: Introductionmentioning

confidence: 99%

Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model

Yu¹,

Zhan

Dong

et al. 2022

JPM

Self Cite

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COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes. There are considerable sex differences among genes in upstream regulation, Ace2 complex interaction, and downstream pathways. Snap25 and Plcb4 may play important roles in the regulation of the expression level of Adam17, Tmprss2, and Cd146 in females. In males, Adh4 is a candidate gene for the regulation of Adam17, while Asl, Auts2, and Rabger1 are candidates for Tmprss2. Within the Ace2 complex, Cd146 directly influences the expression level of Adam17 and Ace2 in the female, while in the male Adam potentially has a stronger influence on Ace2 than that of Tmprss2. Among the top 100 most related genes, only one or two genes from four key genes and 11 from the control B-Actin were found to be the same between sexes. Among the top 10 sets of genes in the downstream pathway of Ace2, only two sets are the same between the sexes. We concluded that these known key genes and novel genes in CKD may play significant roles in the sex difference in the CKD and COVID-19 disease pathways.

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Sex Differences in Correlation with Gene Expression Levels between Ifi200 Family Genes and Four Sets of Immune Disease-Relevant Genes

Cited by 9 publications

References 46 publications

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model

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