A candidate gene identification strategy utilizing mouse to human big-data mining: "3R-tenet" in COPD genetic research.

ABSTRACT: BACKGROUND:Early life impairments leading to lower lung function by adulthood are considered as risk factors for chronic obstructive pulmonary disease (COPD). Recently, we compared the lung transcriptomic profile between two mouse strains with extreme total lung capacities to identify plausible pulmonary function determining genes using microarray analysis (GSE80078). Advancement of high-throughput techniques like deep sequencing (eg. RNA-seq) and microarray have resulted in an explosion of genomic data in the online public repositories which however remains under-exploited. Strategic curation of publicly available genomic data with a mouse-human translational approach can effectively implement "3R- Tenet" by reducing screening experiments with animals and performing mechanistic studies using physiologically relevant in vitro model systems. Therefore, we sought to analyze the association of functional variations within human orthologs of mouse lung function candidate genes in a publicly available COPD lung RNA-seq data-set. METHODS:Association of missense single nucleotide polymorphisms, insertions, deletions, and splice junction variants were analyzed for susceptibility to COPD using RNA-seq data of a Korean population (GSE57148). Expression of the associated genes were studied using the Gene Paint (mouse embryo) and Human Protein Atlas (normal adult human lung) databases. The genes were also assessed for replication of the associations and expression in COPD-/mouse cigarette smoke exposed lung tissues using other datasets. RESULTS:Significant association (p 

SUBMITTER: Vishweswaraiah S 

PROVIDER: S-EPMC5989378 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature