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Genetics Research is a fully open access journal providing a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations, developmental, evolutionary, and population genetics as well as ethical, legal and social aspects.
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Condition-Specific Molecular Network Analysis Revealed That Flagellar Proteins Are Involved in Electron Transfer Processes of Shewanella piezotolerans WP3
Because of the ability to metabolize a large number of electron acceptors such as nitrate, nitrite, fumarate, and metal oxides, Shewanella species have attracted much attention in recent years. Generally, the use of these electron acceptors is mainly achieved through electron transfer proteins and their interactions which will dynamically change across different environmental conditions in cells. Therefore, functional analysis of condition-specific molecular networks can reveal biological information on electron transfer processes. By integrating expression data and molecular networks, we constructed condition-specific molecular networks for Shewanella piezotolerans WP3. We then identified condition-specific key genes and studied their potential functions with an emphasis on their roles in electron transfer processes. Functional module analysis showed that different flagellar assembly modules appeared under these conditions and suggested that flagellar proteins are important for these conditions. We also identified the electron transfer modules underlying these various environmental conditions. The present results could help with screening electron transfer genes and understanding electron transfer processes under various environmental conditions for the Shewanella species.
The Identification of Childhood Asthma Progression-Related lncRNAs and mRNAs Suitable as Biomarkers Using Weighted Gene Coexpression Network Analysis
Background. Asthma is a common chronic respiratory disease in children, seriously affecting children’s health and growth. This bioinformatics study aimed to identify potential RNA candidates closely associated with childhood asthma development within current gene databases. Methods. GSE65204 and GSE19187 datasets were screened and downloaded from the NCBI GEO database. Differentially expressed long noncoding RNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) were identified using the Bioconductor limma package in R, and these DE-mRNAs were used to perform biological process (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Thereafter, weighted gene coexpression network analysis (WGCNA) was utilized to screen the modules directly related to childhood asthma, and a coexpression network of DE-lncRNAs and DE-mRNAs was built. Finally, principal component analysis (PCA) was performed. Results. In total, 7 DE-lncRNAs and 1060 DE-mRNAs, as well as 7 DE-lncRNAs and 1027 DE-mRNAs, were identified in GSE65204 and GSE19187, respectively. After comparison, 336 overlapping genes had the same trend of expression, including 2 overlapped DE-lncRNAs and 334 overlapped DE-mRNAs. These overlapped DE-mRNAs were enriched in 28 BP and 12 KEGG pathways. Eleven modules were obtained in GSE65204, and it was found that the purple, black, and yellow modules were significantly positively correlated with asthma development. Subsequently, a coexpression network including 63 DE-mRNAs and 2 DE-lncRNAs was built, and five KEGG pathways, containing 8 genes, were found to be directly associated with childhood asthma. The PCA further verified these results. Conclusion. LncRNAs LINC01559 and SNHG8 and mRNAs VWF, LAMB3, LAMA4, CAV1, ALDH1A3, SMOX, GNG4, and PPARG were identified as biomarkers associated with the progression of childhood asthma.
Association between the PLTP rs4810479 SNP and Serum Lipid Traits in the Chinese Maonan and Han Populations
The association between the phospholipid transfer protein (PLTP) gene rs4810479 single-nucleotide polymorphism (SNP) and serum lipid levels is largely unknown. This investigation aimed to evaluate the relationship between the PLTP rs4810479 SNP, several environmental risk factors, and serum lipid parameters in the Chinese Maonan and Han nationalities. Polymerase chain reaction-restriction fragment length polymorphism, gel electrophoresis, and direct sequencing were employed to determine the PLTP rs4810479 genotypes in 633 Maonan and 646 Han participants. The frequencies of CC, CT, and TT genotypes and the C allele were different between Maonan and Han groups (29.07%, 53.08%, 17.85%, and 55.61% vs. 35.60%, 49.70%, 14.70%, and 60.45%, respectively, ). The C allele carriers in the Maonan group had higher high-density lipoprotein cholesterol levels than the C allele noncarriers, but this finding was only found in Maonan males but not in females. The C allele carriers in Han males had lower total cholesterol and low-density lipoprotein cholesterol levels than the C allele noncarriers. Serum lipid profiles were also affected by several traditional cardiovascular risk factors in both populations. There might be an ethnic- and/or sex-specific association between the PLTP rs4810479 SNP and serum lipid traits.
Association of AFF3 Gene Polymorphism rs10865035 with Rheumatoid Arthritis: A Population-Based Case-Control Study on a Pakistani Cohort
Rheumatoid arthritis (RA) is one of the complex diseases with the involvement of the genetic as well as environmental factors in its onset and severity. Different genome-wide association and candidate gene studies have shown the role of several genetic variants in multiple loci/genes with ethnical and geographical variations. This study was designed to detect the association of a single-nucleotide polymorphism (SNP) rs10865035 in the AFF3 gene with the genetic background of rheumatoid arthritis (RA) in the Pakistani cohort. A total of 703 individuals, including 409 RA patients and 294 healthy controls, were genotyped using TaqMan assay and Tri primer ARMS-PCR (amplification-refractory mutation system-polymerase chain reaction) methods. The association of rs10865035 with the RA was statistically determined using different models. Interestingly, besides the homozygous recessive model (G/G vs. A/G + A/A) (OR = 1.693(1.06–2.648); = 0.025), all other models, which included the codominant (χ2 = 5.169; = 0.075), homozygous dominant (A/A vs. G/G + A/G) (OR = 0.867 (0.636–1.187); = 0.41), heterozygous (A/G vs. A/A + GG) (OR = 0.491 (0.667–1.215); = 0.49), and additive model (OR = 0.826 (0.665–1.027); = 0.08) showed insignificant distribution of the genotypes among the cases and controls. These findings suggest that the AFF3 gene (rs10865035) has no significant role in the onset of RA in the Pakistani population.
trans-Acting Factors and cis Elements Involved in the Human Inactive X Chromosome Organization and Compaction
During X chromosome inactivation, many chromatin changes occur on the future inactive X chromosome, including acquisition of a variety of repressive covalent histone modifications, heterochromatin protein associations, and DNA methylation of promoters. Here, we summarize trans-acting factors and cis elements that have been shown to be involved in the human inactive X chromosome organization and compaction.
Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ ( = 0.04 for rs2114724 and = 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered ( ≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females ( = 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T–T/T and T/T–C/T ( = 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T–T/T (homozygous minor allele), C/T–C/T (heterozygous), and C/C–C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.