<i>Apolipoprotein E</i> Gene Variants on the Risk of End Stage Renal Disease

<div><p>Objective</p><p>End-stage renal disease (ESRD) is a severe health concern over the world. Associations between apolipoprotein E (apoE) gene polymorphisms and the risk of ESRD remained inconclusive. This study aimed to investigate the association between <i>apoE</i> gene polymorphisms and ESRD susceptibility.</p> <p>Methods</p><p>Databases including PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. Meta-analysis method was used synthesize the eligible studies. </p> <p>Results</p><p>Sixteen pertinent case-control studies which included 3510 cases and 13924 controls were analyzed. A significant association was found between ε2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence interval (CI) 1.15–1.46, <i>P</i> < 0.0001; <i>I</i>² = 18%, <i>P</i> for heterogeneity = 0.24). The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31–2.10, <i>P</i> < 0.0001; OR = 1.62, 95% CI 1.31–2.01, <i>P</i> < 0.0001, respectively), but not in Caucasians. E2 carriers had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, <i>P</i> = 0.0002) than the (ε3 + ε4) carriers in patients with ESRD. The publication bias was not significant.</p> <p>Conclusion</p><p>The ε2 allele of <i>apoE</i> gene might increase the risk of ESRD. E2 carriers expressed higher level of plasma apoE in patients with ESRD. More well-designed studies are needed to confirm these associations in the future.</p> </div

Genome-Wide Characterization of Insertion and Deletion Variation in Chicken Using Next Generation Sequencing

<div><p>Insertion and deletion (INDEL) is one of the main events contributing to genetic and phenotypic diversity, which receives less attention than SNP and large structural variation. To gain a better knowledge of INDEL variation in chicken genome, we applied next generation sequencing on 12 diverse chicken breeds at an average effective depth of 8.6. Over 1.3 million non-redundant short INDELs (1–49 bp) were obtained, the vast majority (92.48%) of which were novel. Follow-up validation assays confirmed that most (88.00%) of the randomly selected INDELs represent true variations. The majority (95.76%) of INDELs were less than 10 bp. Both the detected number and affected bases were larger for deletions than insertions. In total, INDELs covered 3.8 Mbp, corresponding to 0.36% of the chicken genome. The average genomic INDEL density was estimated as 0.49 per kb. INDELs were ubiquitous and distributed in a non-uniform fashion across chromosomes, with lower INDEL density in micro-chromosomes than in others, and some functional regions like exons and UTRs were prone to less INDELs than introns and intergenic regions. Nearly 620,253 INDELs fell in genic regions, 1,765 (0.28%) of which located in exons, spanning 1,358 (7.56%) unique Ensembl genes. Many of them are associated with economically important traits and some are the homologues of human disease-related genes. We demonstrate that sequencing multiple individuals at a medium depth offers a promising way for reliable identification of INDELs. The coding INDELs are valuable candidates for further elucidation of the association between genotypes and phenotypes. The chicken INDELs revealed by our study can be useful for future studies, including development of INDEL markers, construction of high density linkage map, INDEL arrays design, and hopefully, molecular breeding programs in chicken.</p></div

SNP to INDEL ratio.

<p>The ratios were plotted based on the non-redundant (Union) data and the data averaged by chickens (Average), respectively. A: SNP to INDEL ratio across chromosomes. B: SNP to INDEL ratios in functional categories.</p

Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

Egg number (EN), egg laying rate (LR) and age at first egg (AFE) are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS) was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens

One-way sensitivity analysis for the ε2 allele and ESRD risk.

<p>One-way sensitivity analysis for the ε2 allele and ESRD risk.</p

Cumulative meta-analysis of associations between the ε2 allele and ESRD risk.

<p>Cumulative meta-analysis of associations between the ε2 allele and ESRD risk.</p

INDEL and SNP density in each chromosome.

<p>Densities were calculated as the number per 10 kb (INDEL) and kb (SNP), respectively. Densities are averaged by chicken individuals and corrected by read depth. Coverage was calculated based on Q20 reads.</p

Flow chart of the study identification, inclusion, and exclusion.

<p>Flow chart of the study identification, inclusion, and exclusion.</p

Distribution of INDEL length.

<p>INDELs with multiple genotypes were not included.</p