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Global gene-expression analysis has shown remarkable difference between males and females in response to exposure to many diseases. Nevertheless, gene expression studies in asthmatics have so far focused on sex-combined analysis, ignoring inherent variabilities between the sexes, which potentially drive disparities in asthma prevalence. The objectives of this study were to identify (1) sex-specific differentially expressed genes (DEGs), (2) genes that show sex-interaction effects and (3) sex-specific pathways and networks enriched in asthma risk. We analyzed 711 males and 689 females and more than 2.8 million transcripts covering 20 000 genes leveraged from five different tissues and cell types (i.e. epithelial, blood, induced sputum, T cells and lymphoblastoids). Using tissue-specific meta-analysis, we identified 439 male- and 297 female-specific DEGs in all cell types, with 32 genes in common. By linking DEGs to the genome-wide association study (GWAS) catalog and the lung and blood eQTL annotation data from GTEx, we identified four male-specific genes (FBXL7, ITPR3 and RAD51B from epithelial tissue and ALOX15 from blood) and one female-specific gene (HLA-DQA1 from epithelial tissue) that are disregulated during asthma. The hypoxia-inducible factor 1 signaling pathway was enriched only in males, and IL-17 and chemokine signaling pathways were enriched in females. The cytokine-cytokine signaling pathway was enriched in both sexes. The presence of sex-specific genes and pathways demonstrates that sex-combined analysis does not identify genes preferentially expressed in each sex in response to diseases. Linking DEG and molecular eQTLs to GWAS catalog represents an important avenue for identifying biologically and clinically relevant genes.
This article was published in the following journal.
Name: Human molecular genetics
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To reveal the genetic determinants of the treatment outcome of escitalopram in depressed patients (by using candidate gene approach and whole genome scanning).
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An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.
MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENETIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with POLYMERASE CHAIN REACTION.
The use of techniques that produce a functional MUTATION or an effect on GENE EXPRESSION of a specific gene of interest in order to identify the role or activity of the gene product of that gene.
Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.
The pattern of GENE EXPRESSION at the level of genetic transcription in a specific organism or under specific circumstances in specific cells.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...