ALBERT

Description: Background: The genomic information which is transcribed into the primary RNA can be altered by RNA editing at the transcriptional or post-transcriptional level, which provides an effective way to create transcript diversity in an organism. Altering can occur through substitutional RNA editing or via the insertion or deletion of nucleotides relative to the original template. Taking advantage of recent high throughput sequencing technology combined with bioinformatics tools, several groups have recently studied the genome-wide substitutional RNA editing profiles in human. However, while insertional/deletional (indel) RNA editing is well known in several lower species, only very scarce evidence supports the existence of insertional editing events in higher organisms such as human, and no previous work has specifically focused on indel differences between RNA and their matching DNA in human. Here, we provide the first study to examine the possibility of genome-wide indel RNA-DNA differences in one human individual, NA12878, whose RNA and matching genome have been deeply sequenced. Results: We apply different computational tools that are capable of identifying indel differences between RNA reads and the matching reference genome and we initially find hundreds of such indel candidates. However, with careful further analysis and filtering, we conclude that all candidates are false-positives created by splice junctions, paralog sequences, diploid alleles, and known genomic indel variations. Conclusions: Overall, our study suggests that indel RNA editing events are unlikely to exist broadly in the human transcriptome and emphasizes the necessity of a robust computational filter pipeline to obtain high confidence RNA-DNA difference results when analyzing high throughput sequencing data as suggested in the recent genome-wide RNA editing studies.

Description: Background: The CYP7A1 gene polymorphism has been reported to be associated with gallbladder stone disease (GSD) and serum lipid levels, but the results were inconsistent. This meta-analysis aimed to evaluate the influence of the -204A 〉 C polymorphism in the promoter of CYP7A1 gene on the GSD and serum lipid levels. Methods: According to inclusion/exclusion criteria, eligible studies on CYP7A1 gene -204A 〉 C polymorphism of serum lipid levels and the risk of GSD were retrieved. Depending on the between-study heterogeneity, the fixed- or random-effects model was applied, and the data were analyzed using the RevMan software (V5.2). Results: Five studies totaling 830 GSD patients and 882 healthy controls were used to evaluate the relation of CYP7A1 -204A 〉 C polymorphism with GSD. Overall comparison of alleles A with C in all study population yielded 5% but non-significant increased risk of GSD (OR = 1.05, 95% CI: 0.91--1.22, P = 0.48). Subgroup analysis by ethnic differences did not show any association between CYP7A1 -204A 〉 C polymorphism and GSD either. Four studies totaling 802 cases and 691 controls were used to assess the relation of CYP7A1 -204A 〉 C polymorphism with serum lipid levels. All the subjects were from the Asian population. The pooled effects indicated that AC genotype had higher levels of TG than AA (MD = -0.42, 95% CI: -0.76---0.08, P = 0.01). CC genotype in cases had higher levels of TC (MD = 0.65, 95% CI: 0.25--1.05, P = 0.001) and LDL-C (MD = 0.40, 95% CI: 0.06--0.73, P = 0.02) than AA, AA (MD = -0.35, 95% CI: -0.60---0.10, P = 0.007) and AC (MD = -0.35, 95% CI: -0.61---0.08, P = 0.01) genotypes in controls had higher levels of TC than CC, and AA genotype in controls had higher levels of HDL-C than CC (MD = -0.15, 95% CI: -0.21---0.09, P 〈 0.00001). Conclusions: The CYP7A1 -204A 〉 C polymorphism is significantly associated with serum lipid levels in Asian population, but not gallbladder stone disease.