RESUMEN
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Asunto(s)
Humanos , Adenocarcinoma del Pulmón/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Objective Deletion detection and annotation of 18 lines from the population of specific chromosome 1 substitution strains ( PCSSs) derived from Chinese wild mice based on whole genome re-sequencing data. Methods Whole genome re?sequencing of the 18 lines were performed on the Illumina Hiseq platform. SpeedSeq software was used to detect the deletion after read alignment. Further annotation was obtained using SnpEff software. Results 13803 dele?tions were identified among the 18 lines, the length of deletion was ranged from 51bp to 70 kb, among them nearly 50%were less than 500 bp. Through functional annotation,we found most of the variants were located in intronic (50. 361%) and intergenic (28. 745%) regions. However, we also identified 31 protein coding genes harboring loss?of?function dele?tions. Among them, 3 genes were associated with human diseases, 7 genes were participated in 11 KEGG pathways. Conclusion The chromosome 1 of PCSSs harbors abundant deletion mutations which can be used as genetic markers in genetic studies.
RESUMEN
Bambusa emeiensis is one of the preponderant species of sympodial bamboos in Sichuan province of China, and has excellent fiber length and quality as raw materials for papermaking, textile and other industries. In this study, with the application of Illumina HiSeq™ 2000 platform, we analyzed transcriptome in B. emeiensis with different heights of 10, 50, 100 and 150 cm. A total of 69.28 M reads were obtained, and a sum up of 111 137 bands of Unigenes were acquired following de novo stitching, assembly and clustering, among which there were 63 094 bands that had been integrated in the COG, GO, KEGG, Swiss-Prot and Nr databases using annotated methods. These Unigenes not only had general functions, such as transcription and signal transduction, but were also involved in sucrose transport and metabolism, secondary metabolites and cell wall biosynthesis. There was significant difference regarding the expression of cellulose synthase gene in B. emeiensis at different heights, relevant genes were found that might be responsible for the regulation of the growth and development of B. emeiensis as well as the biosynthesis of cellulose and lignin. Our findings could provide some elementary theories for breed improvement of B. emeiensis.