Schizophrenia (SZ) onset and treatment outcome have important genetic components, however individual genes do not have strong effects on SZ phenotype. Therefore, it is important to use the ...pathway‐based approach and study metabolic and signaling pathways, such as dopaminergic and serotonergic. Serotonin pathway has an important role in brain signaling, nevertheless, its role in SZ is not as thoroughly examined as that of dopamine pathway. In this study, we reviewed serotonin pathway genes and genetic variations associated with SZ, including variations at DNA, RNA, and epigenetic level. We obtained 30 serotonin pathway genes from Kyoto encyclopedia of genes and genomes and used these genes for the literature review. We extracted 20 protein coding serotonin pathway genes with genetic variations associated with SZ onset, development, and treatment from 31 research papers. Genes associated with SZ are present on all levels of serotonin pathway: serotonin synthesis, transport, receptor binding, intracellular signaling, and reuptake; however, regulatory genes are poorly researched. We summarized common challenges of genetic association studies and presented some solutions. The analysis of reported serotonin pathway‐SZ associations revealed lack of information about certain serotonin pathway genes potentially associated with SZ. Furthermore, it is becoming clear that interactions among serotonin pathway genes and their regulators may bring further knowledge about their involvement in SZ.
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•The DeepSAV predictor of SAV functional impact was updated and improved.•The diversity of multiple sequence alignment is an important factor in DeepSAV performance.•DBSAV provides ...DeepSAV scores for human SAVs and GTS scores for human genes.•DBSAV is a valuable resource for mechanistic interpretation of human SAVs.
Deleterious single amino acid variation (SAV) is one of the leading causes of human diseases. Evaluating the functional impact of SAVs is crucial for diagnosis of genetic disorders. We previously developed a deep convolutional neural network predictor, DeepSAV, to evaluate the deleterious effects of SAVs on protein function based on various sequence, structural, and functional properties. DeepSAV scores of rare SAVs observed in the human population are aggregated into a gene-level score called GTS (Gene Tolerance of rare SAVs) that reflects a gene's tolerance to deleterious missense mutations and serves as a useful tool to study gene-disease associations. In this study, we aim to enhance the performance of DeepSAV by using expanded datasets of pathogenic and benign variants, more features, and neural network optimization. We found that multiple sequence alignments built from vertebrate-level orthologs yield better prediction results compared to those built from mammalian-level orthologs. For multiple sequence alignments built from BLAST searches, optimal performance was achieved with a sequence identify cutoff of 50% to remove distant homologs. The new version of DeepSAV exhibits the best performance among standalone predictors of deleterious effects of SAVs. We developed the DBSAV database (http://prodata.swmed.edu/DBSAV) that reports GTS scores of human genes and DeepSAV scores of SAVs in the human proteome, including pathogenic and benign SAVs, population-level SAVs, and all possible SAVs by single nucleotide variations. This database serves as a useful resource for research of human SAVs and their relationships with protein functions and human diseases.
The objective of the present study was to estimate the correlation coefficients and assess agro-morphological variability of single cross hybrids of maize. This study was conducted at research field ...of National Maize Research Program, Rampur, Chitwan, Nepal during the winter season from October 6, 2015 to March 5, 2016. Fourteen single cross maize hybrids were evaluated to study correlation and agro-morphological traits. Single cross hybrid namely RML-98 / RL-105 (6229 kg ha-1) significantly produced the highest yield, followed by RM1-4 / NML-2 (6073 kg ha-1), RML-95 / RL-105 (5904 kg ha-1) and RML-5/RL-105 (5528 kg ha-1). Cob length was strongly correlated with cob diameter (0.885), number of kernels per row (0.812), number of kernel rows per cob (0.951), test weight (0.870) and grain yield (0.916). Similarly, cob diameter was strongly correlated with number of kernels per row (0.870), number of kernel rows per cob (0.934), test weight (0.922) and grain yield (0.946). The number of kernels per row was strongly correlated with number of kernel rows per cob (0.915), test weight (0.781) and grain yield (0.847). The number of kernel rows per cob was strongly correlated with test weight (0.902) and grain yield (0.942). Similarly, test weight was strongly correlated with grain yield (0.968). The grain yield of the evaluated hybrids was significantly positively correlated with yield attributing traits. There was considerable variability among the hybrids evaluated for growth, grain yield, and traits indicating the presence of variation. Therefore, the results of this study suggest that farmers should grow maize hybrids RML-98 / RL-105, RM1-4 /NML-2, RML-95 / RL-105 and RML-5/RL-105 to achieve higher maize production.
Metabolic alterations encountered in tumors are well recognized and considered as a hallmark of cancer. In addition to Warburg Effect, epidemiological and experimental studies support the crucial ...role of lipid metabolism in colorectal cancer (CRC). The overexpression of four lipid metabolism-related genes (
and
genes) has been proposed as prognostic marker of stage II CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic and genomic scenarios of
,
,
and
genes, we performed a transcriptomic meta-analysis in more than one thousand CRC individuals. Additionally we analyzed their genomic coding sequence in 95 patients, to find variants that could orchestrate CRC prognosis. We found that genetic variant rs3071, located on
gene, defines a 9.77% of stage II CRC patients with high risk of death. Moreover, individuals with upregulation of
and
expression have an increased risk of CRC recurrence, independently of tumor stage.
emerges as one of the main contributors to signature's prognostic effect. Indeed, both high
expression and presence of tumoral genetic variants located in
coding region, seem to be associated with CRC risk of death. In addition the non-synonymous polymorphism rs2230808, located on
, is associated with gene expression. Patients carrying at least one copy of minor allele showed higher levels of
expression than patients carrying homozygous major allele. This study broaden the prognostic value of
and
genes, independently of CRC tumor stage, leading to future precision medicine approaches and "omics"-guided therapies.
Regulation of glucose metabolism by NAD-dependent ADP-ribosyltransferase is well investigated in different populations. Genetic variations NAD + ADP-ribosyltransferase has been shown to alter the ...activity of the enzyme and associated with susceptibility to diabetes. However, reports on neonatal diabetes are minimal. We, therefore, in the present report aimed to investigate the involvement of NAD + ADP-ribosyltransferase variants as a possible risk factor for predisposition to neonatal diabetes mellitus in Chinese patients. Neonatal subjects diagnosed with diabetes mellitus and healthy infants from a similar geographical area were enrolled at China-Japan Union Hospital of Jilin University, China. The involvement of NAD + ADP-ribosyltransferase with neonatal diabetes mellitus was investigated in DNA samples of all participants by PCR methods. One hundred Twenty neonatal diabetes mellitus cases and a matched number of healthy neonates were enrolled in the present study. GG and G SNPs of NAD + ADP-ribosyltransferase were mainly involved in developing neonatal diabetes mellitus and the individuals with GA SNPs protect responsible for protecting from neonatal diabetes mellitus. Thus, NAD + ADP-ribosyltransferase involved in neonatal diabetes mellitus and risk of developing is approx. 2 times higher compared to healthy subjects. Our finding showed that polymorphism in NAD + ADP-ribosyltransferase gene is associated with the predisposition to neonatal diabetes mellitus in Chinese. The present study also suggested that NAD + ADP-ribosyltransferase is a promising target for the treatment of neonatal diabetes mellitus and an effective care of patients. Our study results encourage conducting further investigation in the multi-centric clinical genetic study including larger samples to assesses the role of NAD + ADP-ribosyltransferase polymorphism in neonatal diabetes mellitus.
•The U-box gene family was firstly identified in wild emmer wheat and other 3 triticum species.•Segmental duplication and polyploidization mainly contributed to the expansion of U-box family in wild ...emmer wheat.•Expression patterns and co-expression network of the TdPUBs were comprehensively investigated using RNA-seq samples and the stress-responsive candidates were obtained.•Genetic variation analysis of U-box genes based on the public resequencing data showed that significant genetic bottleneck has occurred during evolution process of tetraploid wheat.
In this study, 82 U-box genes were identified in wild emmer wheat (TdPUBs) through a genome-search method. Phylogenetic analysis classified them into seven groups and the genes belonging to the same group shared the similar exon–intron structure, motif organization and cis-element compositions. Synteny analysis of the U-box genes between different species revealed that segmental duplication and polyploidization mainly contributed to the expansion of TdPUBs. Furthermore, the genetic variations of U-box were investigated in wild emmer, domesticated emmer and durum wheat. Results showed that significant genetic bottleneck has occurred during domestication process of tetraploid emmer wheat. Meanwhile, 12 TdPUBs were co-located with known domestication related QTLs. Finally, the tissue-specific and stress-responsive TdPUB genes were identified through RNA-seq analysis. Combined with qPCR validation of 19 salt-responsive TdPUBs, the candidates involving in salt response were obtained. It lays the foundation to better understand the regulatory roles of U-box family in emmer wheat and beyond.
Telomere length (TL) is an index of cellular aging and can predict the incidences of many age-related diseases. Change of TL might be affected by environmental pollution and individual's genetic ...background. In this cohort study, we aimed to evaluate the associations between polycyclic aromatic hydrocarbons (PAHs) exposure and longitudinal TL shortening, and investigate whether genetic variations in TERT-CLPTM1L can modify these associations. We measured the baseline concentrations of twelve urinary PAH metabolites and genotyped six variants at TERT-CLPTM1L among 1243 coke-oven workers. The relative leukocyte TL was detected in both baseline and follow-up (4 years later) visits. The TL shortening were estimated by TL decline and TL ratio. We found that the urinary level of 1-hydroxypyrene (1-OHP) had significant dose-response relationships with increased TL decline β(95%CI) = 0.078(0.023, 0.133), P = 0.005 and TL ratio β(95%CI) = 0.096(0.037, 0.155), P = 0.002. Besides, urinary 1-hydroxynaphthalene (1-OHNa) was marginally dose-related with elevated TL decline β(95%CI) = 0.053(-0.001, 0.107), P = 0.055 and TL ratio β(95%CI) = 0.057(-0.002, 0.116), P = 0.058. Analyses of TERT-CLPTM1L variants showed that the rs401681 and rs465498 could modify the effect of 1-OHP on increasing TL decline (Pinteraction = 0.012 and 0.035, respectively) and TL ratio (Pinteraction = 0.014 and 0.067, respectively), which were pronounced among rs401681TT and rs465498CC carriers, but not seen among rs401681TC + CC and rs465498CT + TT carriers. In conclusion, elevated exposure to PAHs can accelerate the TL shortening and this effect can be modified by TERT-CLPTM1L variants. These results may add potential evidence for gene-environment interactions on dynamic changes of telomere length. Further studies are warranted to validate these findings and uncover the underlying mechanisms.
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•A cohort design to study the PAHs-gene interactions on dynamic telomere shortening.•Elevated exposure to PAHs could accelerate 4-year telomere shortening.•Telomere shortening varies in people with distinct rs465498 genotypes.•TERT-CLPTM1L variants interact with PAHs to accelerate 4-year telomere shortening.
PAHs exposure can interact with TERT-CLPTM1L variants to accelerate longitudinal telomere shortening.
The milk casein genes in goats, are highly polymorphic genes with numerous synonymous and non-synonymous mutations. So far, 20 protein variants have been reported in goats for alpha-S1-casein, eight ...for beta-casein, 14 for alpha-S2-casein, and 24 for kappa-casein. This review provides a comprehensive overview on identified milk casein protein variants in goat and non-coding DNA sequence variants with some affecting the expression of the casein genes. The high frequency of some casein protein variants in different goat breeds and geographical regions might reflect specific breeding goals with respect to milk processing characteristics, properties for human nutrition and health, or adaptation to the environment. Because protein names, alongside the discovery of protein variants, go through a historical process, we linked old protein names with new ones that reveal more genetic variability. The haplotypes across the cluster of the four genetically linked casein genes are recommended as a valuable genetic tool for discrimination between breeds, managing genetic diversity within and between goat populations, and breeding strategies. The enormous variation in the casein proteins and genes is crucial for producing milk and dairy products with different properties for human health and nutrition, and for genetic improvement depending on local breeding goals.
•Genetic modifications in genes associated with neurodevelopmental disorders might cause ophthalmic diseases;•Genes associated with brain development and maintenance interact with specific genes and ...metabolic pathways involved in ophthalmic phenotypes;•Genes expressed in the brain and associated with neurodevelopmental disorders are also expressed in distinct parts and stages of eye development;•The diagnose of ophthalmic diseases based on genetic screening requires the use of multiple genetic disease databanks and literature screening;
Changes in the nervous system are related to a wide range of mental disorders, which include neurodevelopmental disorders (NDD) that are characterized by early onset mental conditions, such as schizophrenia and autism spectrum disorders and correlated conditions (ASD). Previous studies have shown distinct genetic components associated with diverse schizophrenia and ASD phenotypes, with mostly focused on rescuing neural phenotypes and brain activity, but alterations related to vision are overlooked. Thus, as the vision is composed by the eyes that itself represents a part of the brain, with the retina being formed by neurons and cells originating from the glia, genetic variations affecting the brain can also affect the vision. Here, we performed a critical systematic literature review to screen for all genetic variations in individuals presenting NDD with reported alterations in vision. Using these restricting criteria, we found 20 genes with distinct types of genetic variations, inherited or de novo, that includes SNP, SNV, deletion, insertion, duplication or indel. The variations occurring within protein coding regions have different impact on protein formation, such as missense, nonsense or frameshift. Moreover, a molecular analysis of the 20 genes found revealed that 17 shared a common protein–protein or genetic interaction network. Moreover, gene expression analysis in samples from the brain and other tissues indicates that 18 of the genes found are highly expressed in the brain and retina, indicating their potential role in adult vision phenotype. Finally, we only found 3 genes from our study described in standard public databanks of ophthalmogenetics, suggesting that the other 17 genes could be novel target for vision diseases.
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