Single Nucleotide Polymorphism Database Research Articles

The evolution of dbSNP: 25 years of impact in genomic research.

The Single Nucleotide Polymorphism Database (dbSNP), established in 1998 by the National Center for Biotechnology Information (NCBI), has been a critical resource in genomics for cataloging small genetic variations. Originally focused on single nucleotide polymorphisms (SNPs), dbSNP has since expanded to include a variety of genetic variants, playing a key role in genome-wide association studies (GWAS), population genetics, pharmacogenomics, and cancer research. Over 25 years, dbSNP has grown to include more than 4.4 billion submitted SNPs and 1.1 billion unique reference SNPs, providing essential data for identifying disease-related genetic variants and studying human diversity. Integrating large-scale projects like 1000 Genomes, gnomAD, TOPMed, and ALFA has expanded dbSNP's catalog of human genetic variation, increasing its usefulness for research and clinical applications. Keeping up with advancements such as next-generation sequencing and cloud-based infrastructure, dbSNP remains a cornerstone of genetic research supporting continued discoveries in precision medicine and population genomics. DATABASE URL: https://www.ncbi.nlm.nih.gov/snp.

Causal relationship between uric acid and stroke: a two-sample mendelian randomization study.

Many previous observational studies have disputed whether there is a link between uric acid and stroke. And the causal relationship between uric acid and stroke is unclear. To determine whether there is a causal relationship between uric acid and stroke by using mendelian randomization (MR). Uric acid dataset was obtained from Anna Kottgen et al, with a sample size of 110,347 people, including 2450,548 single nucleotide polymorphisms (SNPs). Stroke pooled data from Malik R et al, publicly available in MEGASTROKE genome-wide association study, included meta-analysis data from 40,585 stroke patients and 406,111 control patients, totaling 8211,693 SNPs. The summary data of genome-wide association study of uric acid and stroke were collected from publicly available online databases. Inverse variance weighting was used to determine the causal relationship between uric acid and stroke. MR-Egger and weighted median model were used for supplementary analysis. Results were then analyzed for heterogeneity, pleiotropy, and sensitivity to ensure no statistical pleiotropy and to reduce bias. A total of 27 SNPs were included in this study after the disequilibrium instrumental variables were excluded. Check the PhenoScanner database for SNPs associated with confounders. In the end, a total of 8 SNPs were excluded. Two SNPs were excluded because the correction direction was the same. Since the F statistic is >10, rs10761587 and rs1825043 are excluded. Finally, 15 SNPs were selected as uric acid instrumental variables. Inverse variance weighting-fixed effect model suggested that there was no causal relationship between uric acid and stroke (odds ratio = 1.004, 95% confidence interval = 0.940, 1.072). MR-Egger and weighted median model also showed the same result. In addition, the results of this study were robust without heterogeneity and pleiotropy. This MR study suggests no support of a causal relationship between uric acid and stroke.

MiRNASNP-v4: a comprehensive database for miRNA-related SNPs across 17 species.

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) and their target binding sites can influence miRNA biogenesis and target regulation, thereby participating in a variety of diseases and biological processes. Current miRNA-related SNP databases are often species-limited or based on outdated data. Therefore, we updated our miRNASNP database to version 4 by updating data, expanding the species from Homo sapiens to 17 species, and introducing several new features. In miRNASNP-v4, 82580 SNPs in miRNAs and 24836179 SNPs in 3'UTRs of genes across 17 species were identified and their potential effects on miRNA secondary structure and target binding were characterized. In addition, compared to the last release, miRNASNP-v4 includes the following improvements: (i) gene enrichment analysis for gained or lost miRNA target genes; (ii) identification of miRNA-related SNPs associated with drug response and immune infiltration in human cancers; (iii) inclusion of experimentally supported immune-related miRNAsand (iv) online prediction tools for 17 animal species. With the extensive data and user-friendly web interface, miRNASNP-v4 will serve as an invaluable resource for functional studies of SNPs and miRNAs in multiple species. The database is freely accessible at http://gong_lab.hzau.edu.cn/miRNASNP/.

Causality of genetically determined serum metabolites on lower back pain or/and sciatica: a comprehensive Mendelian randomized study.

There is an urgent need to confirm biomarkers reflecting the pathogenesis and targeted drugs of lower back pain or/and sciatica in clinical practice. This study aimed to conduct a two sample bidirectional Mendelian randomization (MR) analysis to explore the causal link between 486 serum metabolites and lower back pain or/and sciatica. All data come from two public shared databases of European ancestry and single nucleotide polymorphisms (SNPs) for lower back pain or/and sciatica acted as instrumental variables. The traditional inverse variance weighting (IVW) method, weighted-median method, MR-Egger methodand other methods were used to estimate causality. The horizontal pleiotropy, heterogeneities were also verified through the MR-Egger intercept test, Cochran's Q test, MR-PRESSO test and the leave-one-out sensitivity analysis. Reverse MR analysis was employed to evaluate the direct impact of metabolites on lower back pain or/and sciatica. Additionally, we conducted the colocalization analysis to reflect the causality deeply. Furthermore, metabolic pathway analysis was performed. 28 metabolites (18 known metabolites, 1 identified metabolites and 9 unknown metabolites) relevant to the risk of sciatica or/and lower back pain after using genetic variants as probes at PIVW < 0.05 were identifed. Among them, 8 serum metabolites decreased risk of sciatica or/and lower back pain significantly (P < 0.05), and 14 serum metabolites increased risk of sciatica or/and lower back pain significantly (P < 0.05). No reverse causal association was found between 28 metabolites and sciatica or/and lower back pain. Colocalization analysis results showed that the associations between sciatica or/and lower back pain and the 28 identified metabolites were not due to shared causal variant sites. Moreover, pathway enrichment analysis identifed 11 signifcant metabolic pathways, which are mainly involved in the pathological mechanism of sciatica or/and lower back pain (P < 0.05). There was no horizontal pleiotropy or heterogeneity in the other analyses. Our analyses provided robust evidence of causal associations between blood metabolites on sciatica or/and lower back pain. However, the underlying mechanisms remain to be further investigated.

Abstract C167: Understanding the effect of single nucleotide polymorphism rs2292596 on the interaction of aryl hydrocarbon receptor repressor and aryl hydrocarbon receptor nuclear translocator

Abstract Lung cancer is the leading cause of cancer death in America. Additionally, the incident rates among Black/African American (B/AA) men and women are significantly higher than those of their white counterparts, despite B/AA’s lower exposure to cigarette smoke (Berg et al, 2010. Journal of Pharmacology and Experimental Therapeutics, Vol. 332, p202). One factor that may increase the risk of lung adenocarcinoma in B/AA individuals is a single nucleotide polymorphism (SNP) found in the aryl hydrocarbon receptor repressor (AHRR) gene. To date, this SNP has been poorly studied, particularly in B/AA individuals. As its name suggests, AHRR represses the detoxification of tobacco smoke induced by aryl hydrocarbon receptor (AHR). Upon exposure to tobacco smoke, AHR enters the nucleus where it dimerizes with aryl hydrocarbon receptor nuclear translocator (ARNT) and binds to xenobiotic response elements (XREs), thereby inducing the genes mediating the detoxification process. Simultaneously, AHRR is turned on as part of a negative feedback loop. AHRR down-regulates the detoxification process by binding to ARNT, forming a negative regulatory complex that binds to XREs. Within the region of AHRR that encodes for the ARNT interaction domain, a single nucleotide polymorphism (SNP) is found in exon 6. SNP rs2292596 encodes a proline or alanine, with 63% of the White subjects having proline while 89% of the B/AA subjects have proline (Single Nucleotide Polymorphism Database, NCBI). As proline is a turn-inducing amino acid, this change, residing in one of the AHRR loops that encircles ARNT, may affect the kinetics of AHRR/ARNT complex association and/or dissociation, thereby potentially affecting the regulatory balance of detoxification. We are currently synthesizing recombinant AHRR protein containing the two different amino acids, along with ARNT. To assess how these changes in the amino acid sequence affect the interaction of AHRR and ARNT, we will measure the association and dissociation rates using a SwitchSense DRX2 instrument. If the SNP affects the kinetics of AHRR/ARNT heterodimer formation, it may affect detoxification and thereby lung cancer risk. If so, in the future the accuracy of lung cancer detection may be improved by increased screening for individuals carrying the risk allele. Furthermore, if the presence of the risk allele implicates a higher risk for lung cancer, this may strengthen lung cancer prevention within the B/AA community. Funding: This research is supported by R21CA290319 from National Institute of Health (NIH)/National Cancer Institute (NCI), the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI, and by the Undergraduate Research Associates Program supported by the USC Provost. Citation Format: Shiori Fukutome, Matthew A. Gladstone, Chunli Yan, Diego A. Velarde, Nicholas Mancuso, Ite Offringa. Understanding the effect of single nucleotide polymorphism rs2292596 on the interaction of aryl hydrocarbon receptor repressor and aryl hydrocarbon receptor nuclear translocator [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C167.

The biomedical relationship corpus of the BioRED track at the BioCreative VIII challenge and workshop.

The automatic recognition of biomedical relationships is an important step in the semantic understanding of the information contained in the unstructured text of the published literature. The BioRED track at BioCreative VIII aimed to foster the development of such methods by providing the participants the BioRED-BC8 corpus, a collection of 1000 PubMed documents manually curated for diseases, gene/proteins, chemicals, cell lines, gene variants, and species, as well as pairwise relationships between them which are disease-gene, chemical-gene, disease-variant, gene-gene, chemical-disease, chemical-chemical, chemical-variant, and variant-variant. Furthermore, relationships are categorized into the following semantic categories: positive correlation, negative correlation, binding, conversion, drug interaction, comparison, cotreatment, and association. Unlike most of the previous publicly available corpora, all relationships are expressed at the document level as opposed to the sentence level, and as such, the entities are normalized to the corresponding concept identifiers of the standardized vocabularies, namely, diseases and chemicals are normalized to MeSH, genes (and proteins) to National Center for Biotechnology Information (NCBI) Gene, species to NCBI Taxonomy, cell lines to Cellosaurus, and gene/protein variants to Single Nucleotide Polymorphism Database. Finally, each annotated relationship is categorized as 'novel' depending on whether it is a novel finding or experimental verification in the publication it is expressed in. This distinction helps differentiate novel findings from other relationships in the same text that provides known facts and/or background knowledge. The BioRED-BC8 corpus uses the previous BioRED corpus of 600 PubMed articles as the training dataset and includes a set of newly published 400 articles to serve as the test data for the challenge. All test articles were manually annotated for the BioCreative VIII challenge by expert biocurators at the National Library of Medicine, using the original annotation guidelines, where each article is doubly annotated in a three-round annotation process until full agreement is reached between all curators. This manuscript details the characteristics of the BioRED-BC8 corpus as a critical resource for biomedical named entity recognition and relation extraction. Using this new resource, we have demonstrated advancements in biomedical text-mining algorithm development. Database URL: https://codalab.lisn.upsaclay.fr/competitions/16381.

Environment influences the genetic structure and genetic differentiation of Sassafras tzumu (Lauraceae)

BackgroundSassafras tzumu, an elegant deciduous arboreal species, belongs to the esteemed genus Sassafras within the distinguished family Lauraceae. With its immense commercial value, escalating market demands and unforeseen human activities within its natural habitat have emerged as new threats to S. tzumu in recent decades, so it is necessary to study its genetic diversity and influencing factors, to propose correlative conservation strategies.ResultsBy utilizing genotyping-by-sequence (GBS) technology, we acquired a comprehensive database of single nucleotide polymorphisms (SNPs) from a cohort of 106 individuals sourced from 13 diverse Sassafras tzumu natural populations, scattered across various Chinese mountainous regions. Through our meticulous analysis, we aimed to unravel the intricate genetic diversity and structure within these S. tzumu populations, while simultaneously investigating the various factors that potentially shape genetic distance. Our preliminary findings unveiled a moderate level of genetic differentiation (FST = 0.103, p < 0.01), accompanied by a reasonably high genetic diversity among the S. tzumu populations. Encouragingly, our principal component analysis painted a vivid picture of two distinct genetic and geographical regions across China, where gene flow appeared to be somewhat restricted. Furthermore, employing the sophisticated multiple matrix regression with randomization (MMRR) analysis method, we successfully ascertained that environmental distance exerted a more pronounced impact on genetic distance when compared to geographical distance (βE = 0.46, p < 0.01; βD = 0.16, p < 0.01). This intriguing discovery underscores the potential significance of environmental factors in shaping the genetic landscape of S. tzumu populations.ConclusionsThe genetic variance among populations of S. tzumu in our investigation exhibited a moderate degree of differentiation, alongside a heightened level of genetic diversity. The environmental distance of S. tzumu had a greater impact on its genetic diversity than geographical distance. It is of utmost significance to formulate and implement meticulous management and conservation strategies to safeguard the invaluable genetic resources of S. tzumu.

Meningoencephalitis in a novel mutation in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) ending a familial diagnostic odyssey: A case series report.

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) is an ultra-rare autosomal recessive disorder that leads to mutations in the nuclear genes encoding thymidine phosphorylase. Symptoms include gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy and asymptomatic leukoencephalopathy. We describe the first case of MNGIE with meningoencephalitis that ultimately led to a familial diagnosis ending a diagnostic odyssey. We retrospectively reviewed the electronic medical records and sent whole exome sequencing for the index case and his family members. We report the variant c.877T>C p.(Cys293Arg) found in TYMP gene in all affected siblings showed typical clinical manifestations related to MNGIE. To the best of our knowledge, this is not described in the literature nor in the population databases dbSNP (Single Nucleotide Polymorphism Database) and gnomAD (Genome Aggregation Database). Additionally, it is located in a highly conserved residue and the bioinformatic analysis suggests it is most probably deleterious. Moreover, we estimated 550 number of cases of MNGIE (including 5 cases in this study) after performing an extensive search in the literature across 3 databases from 1983-2023. In addition, we identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.

FishSNP: a high quality cross-species SNP database of fishes

The progress of aquaculture heavily depends on the efficient utilization of diverse genetic resources to enhance production efficiency and maximize profitability. Single nucleotide polymorphisms (SNPs) have been widely used in the study of aquaculture genomics, genetics, and breeding research since they are the most prevalent molecular markers on the genome. Currently, a large number of SNP markers from cultured fish species are scattered in individual studies, making querying complicated and data reuse problematic. We compiled relevant SNP data from literature and public databases to create a fish SNP database, FishSNP (http://bioinfo.ihb.ac.cn/fishsnp), and also used a unified analysis pipeline to process raw data that the author of the literature did not perform SNP calling on to obtain SNPs with high reliability. This database presently contains 45,690,243 (45 million) nonredundant SNP data for 13 fish species, with 30,288,958 (30 million) of those being high-quality SNPs. The main function of FishSNP is to search, browse, annotate and download SNPs, which provide researchers various and comprehensive associated information.

MISSENSE MUTATIONS IN THE IRAK1 GENE ARE ASSOCIATED WITH AN INCREASED RISK OF SYSTEMIC LUPUS ERYTHEMATOSUS

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation in humans. Missense SNPs can change protein structure and function. This study aimed to determine missense SNPs of the IRAK1 gene that can affect the amino acid sequence and lead to changes in protein structure and function, as well as their relationship as a risk factor for SLE. In this in silico method, several bioinformatics tools have been used to identify missense SNPs, including their properties and impacts, as well as their interaction networks with proteins. The tools used were PolyPhenv2, SIFT, PhD-SNP, PROVEAN, SNAP, Panthers, I-Mutant 3.0, and GeneMania. Four missense SNPs, rs11465830, rs1059702, rs1059703, and 10127175, were obtained from the NCBI SNP database. The SIFT test results showed that all the SNPs were tolerant. In the test results obtained using PolyPhen, the four SNPs were benign. The results of the probe test indicated that the four SNPs were neutral. When tested with SNAP, one SNP was neutral, and three others had an impact. In the PhD-SNP test, all SNPs were neutral. In the panther test, all SNPs were benign. The I-mutant assay showed that the four SNPs could decrease protein stability. Tests with GeneMania have reported that most interactions between genes were between IRAK1 and MYD88, and physical interactions were the most dominant form of interaction. Conclusion. rs10127175, rs11465830, rs1059702, and rs1059703 are missense SNPs in IRAK1, which can disrupt protein stability and be a risk factor for SLE. Keywords: IRAK1, SNP, Missense, Systemic Lupus Erythematosus

Determination of Deleterious SNPs in NUDT15 Gene Related to Acute Lymphoblastic Leukemia by using Bioinformatics Tools

Aim: In acute lymphoblastic leukemia (ALL), thiopurine group drugs are the most basic drugs and are included in almost all treatment protocols, especially in maintenance treatment. The mechanism of action of thioguanine nucleotides is to enter the DNA structure in cells, disrupt DNA synthesis, and trigger programmed cell death. The impact of deleterious SNPs on nucleotide triphosphate diphosphatase protein regarding ALL is not yet fully understood. In this study, it was aimed to determine the possible deleterious impacts of missense variants in the NUDT15 gene on protein structure and stabilization that play a significant role in susceptibility to the disease, using modern bioinformatics software. Method: To access SNPs in the NUDT15, it was used National Center for Biotechnology Information (NCBI), Single Nucleotide Polymorphism Database (dbSNP). In bioinformatics tools used in this study included SIFT, PolyPhen-2, PROVEAN, SNAP2, and PANTHER, followed by I-Mutant, HOPE, and STRING. Results: The results of the analysis showed that in a total of 6663 SNPs in the NUDT15, 6 variants have been identified as ‘deleterious’. According to the I-Mutant software, 4 deleterious SNPs decreased protein stability while 2 deleterious SNPs increased protein stability. In the HOPE database analysis, E115G, E57G, F52L, and K33N mutant amino acids were found to be smaller and more hydrophobic than wild-type amino acids, while G53R and G145D mutant amino acids were found to be larger. Thus, all variations resulted in alterations in the net charge on the NUDT15 protein. Conclusion: Data on NUDT15 variants will contribute to the prediction of the patient’s response to thiopurine drugs in future studies, to a better understanding of the patient’s susceptibility to drug interactions, and ultimately to obtaining information about the prognosis.

Characterizing subgenome recombination and chromosomal imbalances in banana varietal lineages.

Bananas and plantains (Musa spp.) are among the most important crops worldwide. The cultivated varieties are vegetatively propagated, so their genetic diversity is essentially fixed over time. Musa acuminata, M. balbisiana and M. schizocarpa have provided the named A, B and S subgenomes that predominantly constitute these varieties. Here we aimed to characterize intergenetic recombination and chromosomal imbalances between these A/B/S subgenomes, which often result in copy-number variants (CNVs) leading to changes in gene dosage and phenotype, in a diverse panel of bananas and plantains. This will allow us to characterize varietal lineages better and identify sources of genetic variation. We delimited population structure and clonal lineages in a diverse panel of 188 banana and plantain accessions from the most common cultivars using admixture, principal component and phylogenetic analyses. We used new scalable alignment-based methods, Relative Averaged Alignment (RAA) and Relative Coverage, to infer subgenome composition (AA, AAB, etc.) and interspecific recombination. In our panel, we identified ten varietal lineages composed of somatic clones, plus three groups of tetraploid accessions. We identified chromosomal exchanges resulting in gains/losses in chromosomal segments (CNVs), particularly in AAB and ABB varieties. We demonstrated alignment-based RAA and Relative Coverage can identify subgenome composition and introgressions with similar results to more complex approaches based on single nucleotide polymorphism (SNP) databases. These ab initio species-agnostic methods can be used without sequencing a panel of wild ancestors to find private SNPs, or in recently diverged pools where private SNPs are uncommon. The extensive A/B/S exchanges and the variation in the length of some introgressions between lineages further support multiple foundational events of hybridization and residual backcrossing. Imbalances between A/B/S may have resulted in CNVs and gene dosage variation. Since most edible banana genomes are fixed on time, these CNVs are stable genetic variations probably associated with phenotypic variation for future genetic studies.

Human_SNP_TATAdb: a database of SNPs that statistically significantly change the affinity of the TATA-binding protein to human gene promoters: genome-wide analysis and use cases

Human_SNP_TATAdb: a database of SNPs that statistically significantly change the affinity of the TATA-binding protein to human gene promoters: genome-wide analysis and use cases

Genetic linkage between swimming performance and disease resistance enables multitrait breeding strategies in large yellow croaker

Improving the robustness of fish stock has become a key issue in the advancement of aquaculture, as diseases and harsh aquatic conditions impact industry sustainability and yield. In this study, we identify several genetic loci that link swimming performance to disease resistance in large yellow croaker, and apply genomic selection (GS) for swimming performance to generate offspring with both enhanced swimming performance and disease resistance. First, we classified our reference population as superior swimmers (SS) or inferior swimmers (IS) by swimming tests and assessed inherent disease resistance. Consistent with previous research, SS displayed enhanced resistance to the parasite Cryptocaryon irritans. Through genotyping of parental reference and candidate populations, we generated a single nucleotide polymorphism (SNP) database, containing 45832 high-quality SNPs in total. We applied multitrait genome-wide association study analysis of swimming performance and disease resistance to this dataset and identified three linked SNPs, which were associated with 48 potential candidate genes, including pp3r1b, mapk12b, mapk11, and tnfrsf11a. Next, we generated a GS model using the BayesB method and calculated the candidate population's genetic estimated breeding value (GEBV). Individuals with GEBV's in the top 12 ​% were selected as broodstocks for breeding selective lines (SL), and the remaining individuals were used as the control group (CG). We found that SL exhibited both increased swimming performance and resistance to C. irritans compared to CG. Our study reveals the genetic basis related to swimming performance and disease resistance. This work has implications for designing multitrait breeding strategies and improving whole-fish fitness, both of which are critical in aquaculture.

ScSNPdemux: a sensitive demultiplexing pipeline using single nucleotide polymorphisms for improved pooled single-cell RNA sequencing analysis

BackgroundHere we present scSNPdemux, a sample demultiplexing pipeline for single-cell RNA sequencing data using natural genetic variations in humans. The pipeline requires alignment files from Cell Ranger (10× Genomics), a population SNP database and genotyped single nucleotide polymorphisms (SNPs) per sample. The tool works on sparse genotyping data in VCF format for sample identification.ResultsThe pipeline was tested on both single-cell and single-nuclei based RNA sequencing datasets and showed superior demultiplexing performance over the lipid-based CellPlex and Multi-seq sample multiplexing technique which incurs additional single cell library preparation steps. Specifically, our pipeline demonstrated superior sensitivity and specificity in cell-identity assignment over CellPlex, especially on immune cell types with low RNA content.ConclusionsWe designed a streamlined pipeline for single-cell sample demultiplexing, aiming to overcome common problems in multiplexing samples using single cell libraries which might affect data quality and can be costly.

Identification genetic variations in some heat shock protein genes of Tali goat breed and study their structural and functional effects on relevant proteins.

Animals of different regions have adapted to adverse environmental conditions by modifying their phenotypic and genotypic characteristics in the long run. In this study, the effect of genetic variations of 10 heat shock protein (HSP) genes (HSP70A4, HSP70A9, HSP40C17, HSP40C27, HSP90AA1, HSP90AB1, HSPB7, HSPB11, HSPD1 and HSPE1) on the three-dimensional protein structure and function of proteins in Tali goat (a tropical breed) were studied and were compared with Saanen goat (as a sensitive breed). A pooled DNA of 15 samples from blood was sequenced and mapped to the goat reference sequence. The bioinformatics analysis was used to identify nsSNPs in the Tali breed and was compared with the Saanen goat. Four online bioinformatics tools (Sorting Intolerant from Tolerant, Protein Variation Effect Analyzer, Polymorphism Phenotyping version2 and Single Nucleotide Polymorphism Database and Gene Ontology) showed three deleterious missense nsSNPs and seven natural missense SNPs in these HSPs genes of Tali goat. Out of 10 reported nsSNPs, 5 nsSNPs in HSP70A4, 1 nsSNP inHSP70A9, 2 nsSNPs in HSP40C17, 1 nsSNP in HSP40C27 and 1 nsSNP in HSPD1 were detected. ConSurf tools showed that the majority of the predicted nsSNPs occur in conserved sites. Moreover, several post-translational modification (PTM) predictors computed the probability of post-translation change of nsSNPs. The putative phosphorylation and glycosylation sites in HSPs proteins were substitutions rs669769139 and rs666336692 of the Tali goat breed. These results on the effect of type of genetic variants on the function of HSP proteins will assist to predict the resistance to hard conditions in goat breeds. Considering that the identified SNPid rs669769139 (S248) which is located on the N-terminal ATPase domain of HSP70A4 is a PTM site with a highly conserved score and a natural substitution on changing the stability and benign protein that can affect the functional and structural characterization of HSPs protein for adaptation to the local climate.

Tools of genomic medicine for clinical practice: The example of psychiatry.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

The generation of the first chromosome-level de-novo genome assembly and the development and validation of a 50 K SNP array for the St John River aquaculture strain of North American Atlantic salmon.

Atlantic salmon (Salmo salar) in Northeastern US and Eastern Canada has high economic value for the sport fishing and aquaculture industries. Large differences exist between the genomes of Atlantic salmon of European origin and North American (N.A.) origin. Given the genetic and genomic differences between the two lineages, it is crucial to develop unique genomic resources for N.A. Atlantic salmon. Here we describe the resources that we recently developed for genomic and genetic research in N.A. Atlantic salmon aquaculture. Firstly, a new single nucleotide polymorphism (SNP) database for N.A. Atlantic salmon consisting of 3.1 million putative SNPs was generated using data from whole genome resequencing of 80 N.A. Atlantic salmon individuals. Secondly, a high density 50 K SNP array enriched for the genic regions of the genome and containing three sex determination and 61 putative continent of origin markers was developed and validated. Thirdly, a genetic map composed of 27 linkage groups with 36 K SNP markers, was generated from 2,512 individuals in 141 full-sib families. Finally, a chromosome level de-novo genome assembly from a male N.A. Atlantic salmon from the St John River aquaculture strain was generated using PacBio long-reads. Information from Hi-C proximity ligation sequences and Bionano optical mapping was used to concatenate the contigs into scaffolds. The assembly contains 1,755 scaffolds and only 1,253 gaps, with a total length of 2.83 Gb and N50 of 17.2 Mb. A BUSCO analysis detected 96.2% of conserved Actinopterygii genes in the assembly and the genetic linkage information was used to guide the formation of 27 chromosome sequences. Comparative analysis with the reference genome assembly of the European Atlantic salmon confirmed that the karyotype differences between the two lineages are caused by a fission in chromosome Ssa01 and three chromosome fusions including the p arm of chromosome Ssa01 with Ssa23, Ssa08 with Ssa29 and Ssa26 with Ssa28. The genomic resources we have generated for Atlantic salmon provide a crucial boost for genetic research and for management of farmed and wild populations in this highly valued species.

High carrier frequency of pathogenic PATL2 gene mutations predicted in population: a bioinformatics-based approach.

Topoisomerase II homologue 2 (PATL2) has been confirmed to be a key gene that contributes to oocyte maturation. However, the allele distribution and carrier frequency of these mutations remain uncharacterized. So a bioinformatics subcategory analysis of PATL2 mutations from outcome data and Single Nucleotide Polymorphism (SNP) databases was conducted. Altogether, the causative PATL2 mutation number detected in patients with oocyte maturation defects in the clinical studies and pathogenic PATL2 mutation sites predicted by software based on the database was approximately 53. The estimated carrier frequency of pathogenic mutation sites was at least 1.14‰ based on the gnomAD and ExAC database, which was approximately 1/877. The highest frequency of mutations detected in the independent patients was c.223-14_223-2del13. The carrier frequency of this mutation in the population was 0.25‰, which may be a potential threat to fertility. Estimated allele and carrier frequency are relatively higher than those predicted previously based on clinical ascertainment. A review of PATL2 mutation lineage identified in 34 patients showed that 53.81%, 9.22% and 14.72% of the oocytes with PATL2 mutations were arrested at the germinal vesicle (GV) stage, metaphase I (MI) stage and first polar body stage, respectively. Oocytes that could develop to the first polar body stage were extremely rare to fertilise, and their ultimate fate was early embryonic arrest. Phenotypic variability is related to the function of the regions and degree of loss of function of PATL2 protein. A 3D protein structure changes predicted by online tools, AlphaFold, showed aberrations at the mutation sites, which may explain partially the function loss. When the mutated and wild-type proteins are not in the same amino acid category, the protein structure will be considerably unstable. The integration of additional mutation sites with phenotypes is helpful in drawing a complete picture of the disease. Bioinformatics analysis of PATL2 mutations will help reveal molecular epidemiological characteristics and provide an important reference for new mutation assessment, genetic counselling and drug research.

Don't panic any more: MORE PANICLES 3 increases rice yield at elevated CO2 levels.

Don't panic any more: MORE PANICLES 3 increases rice yield at elevated CO2 levels.