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Integrating bioinformatics and multiomics approaches is essential for identifying and prioritizing causal genetic variants in complex traits and diseases. The Pla2g4e gene case study in mice illustrates a practical example of using SNPs within regulatory elements to narrow down causative variants, offering a replicable model for similar genetic research. A hierarchical strategy for identifying and ranking SNP-containing regulatory elements is introduced, effectively narrowing down candidates for functional testing. The proposed approach can accelerate research by reducing the time and resources required for future validation of genetic variants for causality. The review introduces a user-friendly bioinformatics pipeline accessible to researchers at all levels without the need for specialized bioinformatics expertise. This review addresses the significant challenge of identifying causal genetic variants within quantitative trait loci (QTLs) for complex traits and diseases. Despite progress in detecting the ever-larger number of such loci, establishing causality remains daunting. We advocate for integrating bioinformatics and multiomics analyses to streamline the prioritization of candidate genes' variants. Our case study on the Pla2g4e gene, identified previously as a positional candidate obesity gene through genetic mapping and expression studies, demonstrates how applying multiomic data filtered through regulatory elements containing SNPs can refine the search for causative variants. This approach can yield results that guide more efficient experimental strategies, accelerating genetic research toward functional validation and therapeutic development. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis. We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes. Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands. We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlex webtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann–Whitney U test and evaluated survival with Kaplan–Meier curves with the log-rank test and Cox regression. Uveal melanoma-related survival. Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P = 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P = 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P = 0.04) than in patients with an A/G or A/A genotype. The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3). The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

A 44-year-old man with hypertension and dyslipidemia presented with pain in the buttocks. The patient was diagnosed with perianal ischiorectal fossa abscesses and cellulitis. He was subsequently diagnosed with a perineal subcutaneous abscess after a week, a right lower leg impetigo after a month, right periorchitis, a scrotal abscess, and Fournier's gangrene after two months. The patient was treated with various antimicrobials and underwent incisional drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in all draining specimens. Her daughter and son, who lived with the patient, presented with subcutaneous abscesses caused by MRSA. Suspecting repeated infections and household infections by virulent types of MRSA, such as PVL-positive strains, we performed genetic analyses of his and his son's strains. The results showed that the genotype and toxin gene profiles [ST8/t008/SCCmec type IVc/Panton-Valentine leucocidin (PVL) (+)/arginine catabolic mobile element (ACME) (−)] of both strains matched. single nucleotide polymorphism (SNP) analysis confirmed genetic homology between the two, concluding that home transmission by the same clone had occurred. In addition, the strain in this case differed from USA300 [ST8/t008/SCCmec type IVa/PVL (+) ACME (+)], which is a PVL-positive MRSA worldwide, including Japan, and its genetic profile matches that of USA300-LV, which is detected mainly in South America. Furthermore, SNP analysis showed that this strain is similar to USA300-LV/J (derived from USA300-LV) detected on Ishigaki Island, Okinawa Prefecture, Japan. This is the first report of refractory infections and household transmission of USA300-LV/J. Therefore, it is necessary to closely monitor both the USA300 and the USA300-LV. [ABSTRACT FROM AUTHOR]

The dysfunction of the ABO glycosyltransferase (GT) enzyme, which is caused by mutations in the ABO gene, can lead to weak ABO phenotypes. In this study, we have discovered a novel weak ABO subgroup allele and investigated the underlying mechanism to causing its A weak phenotype. The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the novel single nucleotide polymorphism (SNP) was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. The results of serological showed the subject was A weak phenotype. A novel SNP c.424A > G (p. M142V) based on ABO∗A1.02 was identified, and the genotype of the subject was AW-var/O.01 according to the gene analysis. In silico analysis showed that the SNP c.424A > G on the A allele may change the local conformation by damaging the hydrogen bonds and reduce the stability of GT. In vitro expression study showed that SNP p.M142V impaired H to A antigen conversion, although it did not affect the generation of A glycosyltransferase (GTA). One novel AW allele was identified and the SNP c.424A > G (p.M142V) can cause the A weak phenotype through damaging the hydrogen bonds and reducing stability of the GTA. [ABSTRACT FROM AUTHOR]

Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data. The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions. The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3 , KIAA1217 , OPCML , CAMSAP2 , and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E−07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E−6). The SNPs showing significant interactions were located in the KIAA1217 , RBFOX3 , SDK2 , CYP19A1 , NTM , SMYD3 , and RBFOX1 genes. Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary. • Genetic interactions are crucial for the sub-phenotype of psychiatric disorder. • Age at onset of bipolar disorder was influenced by gene-gene interactions. • The SNPs showing significant interactions were located in the KIAA1217 , RBFOX3 , SDK2 , CYP19A1 , NTM , SMYD3 , and RBFOX1 genes. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) pinpointed gastric cancer (GC)-associated single-nucleotide polymorphisms (SNPs) and other gene variants not only in genes of the human host but also in genes of the bacterial pathogen Helicobacter pylori. Functional studies unraveled the underlying mechanisms by which SNPs in H. pylori virulence factors CagA and serine protease HtrA promote GC development. The 171L/S SNP in HtrA originated in Asia 60 000 to 45 000 years ago after the human migration out-of-Africa and spread to all continents except Africa; the EPIYT mutation in CagA arose before the out-of-Africa migration. Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies. [ABSTRACT FROM AUTHOR]

• Brown Planthopper is a serious threat to rice crop, posing a significant risk to food security. • To combat the damage, molecular breeding stands as an efficient approach by utilizing resistance genes. • Accordingly, a sophisticated marker assisted breeding technique was employed with SSRs and SNPs to introduce BPH genes from M229 and 10–3 donors into susceptible Telangana Sona. • Five backcross lines (BC 1 (a)−14, BC 1 (a)−19, BC 1 (b)−2, BC 1 (b)−4, BC 1 (b)−5) from both the crosses were identified as potential materials, displaying grain characteristics similar to Telangana Sona. Brown Planthopper (BPH) is one of the most destructive insect pests of rice that threatens food security. Molecular breeding through the use of resistance genes per se would be an economic and efficient way to combat the damage caused by BPH. Telangana Sona (TS) is an elite, popular and a high yielding rice variety susceptible to the infestation of BPH causing severe yield losses. In the current investigation, a marker-assisted backcross breeding approach using gene-specific Simple Sequence Repeats (SSRs) and designed Single Nucleotide Polymorphisms (SNPs) was employed to incorporate BPH resistance genes from the donor lines, M229 and 10–3 into TS. Foreground selection using gene-specific SSRs pinned down one plant (BC 1 (a)-19) from TS//TS/M229 cross with qBph-3–1 and Bph33(t) genes/QTLs, while, six plants of TS//TS/10–3 cross had Bph33(t) gene. Validation of BC 1 F 1 plants with designed SNPs altogether identified three (BC 1 (a)-14, BC 1 (a)-18, BC 1 (a)-19) from TS//TS/M229 and three lines (BC 1 (b)-2, BC 1 (b)-4, BC 1 (b)-5) from TS//TS/10–3 cross positive for snpOS00915, snpOS00922 and snpOS00923. All these lines were also found to be phenotypically resistant to BPH as screened using a modified mass tiller screening method. Altogether, foreground selection coupled with stringent phenotypic selection and agro-morphological evaluation led to the identification of two backcross lines (BC 1 (a)-14 and BC 1 (a)-19) from TS//TS/M229 and three (BC 1 (b)-2, BC 1 (b)-4, BC 1 (b)-5) from TS//TS/10–3 that had grain type characteristics similar to TS that can be potentially used as breeding material for further backcrossing and advancing for near isogenic lines development. The study demonstrates the potential efficacy of marker-assisted selection deployed with both SSRs and SNPs that can be employed in breeding for BPH-resistant varieties. [ABSTRACT FROM AUTHOR]

Background: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) molecule is a key regulator of the immune response by exerting an inhibitory effect on various types of immune cells. Understanding the role of TIM-3 in hematopoietic stem cell transplantation (HSCT) may improve transplant outcomes. Our study evaluated the potential association between TIM-3 polymorphisms, namely rs1036199 (AC) or rs10515746 (C> A), changes which are located in exon 3 and the promoter region of the TIM-3 gene, and post-HSCT outcomes. Methods: One-hundred and twenty allogeneic HSCT patients and their respective donors were enrolled and genotyped for TIM-3 single nucleotide polymorphisms (SNPs) using real-time PCR with TaqMan assays. Results: We found that the presence of the rare alleles and heterozygous genotypes of studied SNP in recipients tended to protect against or increase the risk for acute graft-versus-host disease (aGvHD). For the rs1036199 polymorphism, recipients with the AC heterozygous genotype (p=0.0287) or carrying the rarer C allele (p = 0.0334) showed a lower frequency of aGvHD development along all I-IV grades. A similar association was detected for the rs10515746 polymorphism as recipients with the CA genotype (p=0.0095) or the recessive A allele (p=0.0117) less frequently developed aGvHD. Furthermore, the rarer A allele of rs10515746 SNP was also associated with a prolonged aGvHD-free survival (p = 0.0424). Cytomegalovirus (CMV) infection was more common in patients transplanted with TIM-3 rs10515746 mismatched donors (p = 0.0229) and this association was also found to be independent of HLA incompatibility and pre-transplant CMV-IgG status. Multivariate an- alyses confirmed the role of these recessive alleles and donor-recipient TIM-3 incompatibility as an independent factor in aGvHD and CMV development. Conclusions: Polymorphism of TIM-3 molecule may affect the immune response in HSCT patients. The recessive alleles of rs1036199 and rs10515746 SNPs decreased the risk of developing aGvHD. TIM-3 donor-recipient genetic matching may also affect the risk of post-transplant CMV infection, indicating the potential value of genetic profiling in optimizing transplant strategies. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological changes. Genetic variations, called single nucleotide polymorphisms (SNPs), influence various hip morphological parameters. This study investigated the biological relevance of SNPs correlated to hip morphology in genome-wide association studies (GWAS). The SNP-associated genes were compared to genes associated with OA in other joints, aiming to see if the same genes play a role in both hip development and the risk of OA in other lower limb joints. A systematic literature review was conducted to identify SNPs correlated with hip morphology, based on the Population, Intervention, Comparison, Outcome, and Study (PICOS) framework. Afterwards, Gene Ontology (GO) analysis was performed, using EnrichR, on the SNP-associated genes and compared with non-hip OA-associated genes, across different databases. Reviewing 49 GWAS identified 436 SNPs associated with hip joint morphology, encompassing variance in bone size, structure and shape. Among the SNP-associated genes, SOX9 plays a pivotal role in size, GDF5 impacts bone structure, and BMP7 affects shape. Overall, skeletal system development, regulation of cell differentiation, and chondrocyte differentiation emerged as crucial processes influencing hip morphology. Eighteen percent of GWAS-identified genes related to hip morphology were also associated with non-hip OA. Our findings indicate the existence of multiple shared genetic mechanisms across hip morphology and OA, highlighting the necessity for more extensive research in this area, as in contrast to the hip, the genetic background on knee or foot morphology remains largely understudied. [ABSTRACT FROM AUTHOR]

ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer. SNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active. DNA repair SNPs reported by at least two independent studies were pooled for meta-analysis. The study endpoint was radiation pneumonitis (RP) after radiotherapy. Recessive, dominant, homozygous, heterozygous, and allelic genotype models were used where appropriate. A total of 16 studies (3080 patients) were identified from the systematic review and 12 studies (2090 patients) on 11 SNPs were included in the meta-analysis. The SNPs were ATM rs189037, ATM rs373759, NEIL1 rs4462560, NEIL1 rs7402844, APE1 rs1130409, XRCC3 rs861539, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, ERCC2 rs13181, and XRCC1 rs25487. ERCC1 rs11615 (236 patients) and ERCC2 rs238406 (254 patients) were not significantly associated with RP. Using the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001). Genetic variation in the DNA repair pathway genes may play a significant role in the risk of developing radiation pneumonitis in patients with lung cancer. Further studies are needed on genotypic features of DNA repair pathway genes and their association with treatment sensitivity, as such knowledge may guide personalized radiation dose prescription. • A total of 16 studies (3080 patients) were identified from the systematic review. • Genetic variation in NEIL1 rs7402844 and APE1 rs1130409 may predict RP. • Need to further elucidate relationship between ERCC1 rs11615, ERCC2 rs238406 with RP. [ABSTRACT FROM AUTHOR]

Previous studies have implicated both rare copy number variations (CNVs) and common variants in liability for attention-deficit/hyperactivity disorder (ADHD). However, how common and rare genetic variants jointly contribute to individual liability requires further investigation in larger cohorts. This study comprises 9385 participants of European descent and 7810 participants of African American ancestry who were recruited from the greater Philadelphia area by the Children's Hospital of Philadelphia. The polygenic risk score (PRS) of each participant was estimated by linkage disequilibrium pruning and p -value thresholding (P + T) methods using PRSice-2. We investigated whether the risk of ADHD follows a polygenic liability threshold model wherein 1) the risk of ADHD requires less contribution from common variants in the presence of a rare CNV, and 2) control carriers of ADHD-associated CNVs have lower common risk allele burden than noncarriers. CNVs previously reported in ADHD cases were significantly associated with ADHD risk in both the European American cohort and the African American cohort. Healthy control participants carrying those same risk CNVs had lower PRSs than those without risk CNVs in the European American cohort. This result was replicated in the African American cohort. However, PRSs were not significantly different in case participants carrying risk CNVs versus those without risk CNVs. These findings provide evidence in support of interactive effects of PRS and ADHD-associated CNVs on disease risk and add novel insights into the genetic basis of ADHD by highlighting a protective role of low PRS in ADHD. [ABSTRACT FROM AUTHOR]

The BMPR1B gene is a major determinant of sheep reproductive capacity. Previous studies revealed that Q249R (FecB) is a profound variant of BMPR1B that influences the ovulation rate and litter size in sheep. However, unlike Q249R locus, the full spectrum of single nucleotide polymorphisms (SNPs) within BMPR1B has not been extensively studied. A systematic screen of SNPs in BMPR1B would facilitate the discovery of novel variants that are associated with litter size. This study aimed to investigate SNPs in the BMPR1B gene via whole genome sequence (WGS) data from 2409 individuals of 75 sheep breeds worldwide. Herein, a total of 9688 variants were screened, among which 15 were coding variants and 8 were novel changes. Specifically, we presented the most comprehensive frequency distribution map of the well-known FecB mutation to date. Besides, among the above-mentioned SNPs, one synonymous mutation (g.30050773C > T) was found to be likely under selection and is potentially associated with fecundity in Duolang sheep. Thus, our study greatly expands the variation repertoire of the ovine BMPR1B gene and provides a valuable resource for exploring causative mutations and genetic markers associated with litter size. • A repertoire of SNPs of BMPR1B gene were provided by analyzing whole genome sequence data from 2409 individuals of 75 populations worldwide. • A total of 9688 variants were screened, among which 15 were coding variants and 8 were novel changes. • The distribution frequency of FecB mutation among global populations is provided. [ABSTRACT FROM AUTHOR]

We assessed aging hallmarks in skin, muscle, and adipose in the genetically diverse HET3 mouse, and generated a broad dataset comparing these to individual animal diagnostic SNPs from the 4 founding inbred strains of the HET3 line. For middle- and old-aged HET3 mice, we provided running wheel exercise to ensure our observations were not purely representative of sedentary animals, but age-related phenotypes were not improved with running wheel activity. Adipose tissue fibrosis, peripheral neuropathy, and loss of neuromuscular junction integrity were consistent phenotypes in older-aged HET3 mice regardless of physical activity, but aspects of these phenotypes were moderated by the SNP% contributions of the founding strains for the HET3 line. Taken together, the genetic contribution of founder strain SNPs moderated age-related phenotypes in skin and muscle innervation and were dependent on biological sex and chronological age. However, there was not a single founder strain (BALB/cJ, C57BL/6J, C3H/HeJ, DBA/2J) that appeared to drive more protection or disease-risk across aging in this mouse line, but genetic diversity in general was more protective. [Display omitted] • Genetically diverse HET3 mice are susceptible to age-related neuromuscular decline. • Voluntary exercise was ineffective at preventing age-related neuromuscular decline. • Relative contributions of HET3 founder strain genetics moderated neuropathy onset. [ABSTRACT FROM AUTHOR]

Over the last few decades, there has been a constant increase in sow litter size, the consequences of which include parturition duration extension, an increase in the percentage of stillborn and hypoxic piglets, and increased variation in piglet birth weight, which reduces their vitality. As such, it seems clear that further increasing sow fertility will generate difficulties and costs in rearing numerous litters with low birth weights. Therefore, the current study aimed to analyze the genetic background of sow hyperprolifcacy using a genome-wide association study (GWAS). The research included 144 sows in the maternal component, divided into two equal groups. The first group (control) consisted of females giving birth to the optimal number of piglets in their third and fourth litters (14–16), while the second group (cases) included those with excessive litter size (>16). The analyzed sows were genotyped using Illumina's PorcineSNP60v2 BeadChip microarray, comprising 64,232 single nucleotide polymorphisms (SNPs). Statistical analysis using R included quality control of genotyping data and GWAS analysis based on five logistic regression models (dominant, codominant, overdominant, recessive, and log-additive) with a single SNP marker as the explanatory variable. On this basis, one SNP (SIRI0000069) was identified on chromosome seven within the EFCAB11 (EF-hand calcium binding domain 11) gene that had a statistically significant effect on sow hyperprolificacy. Additionally, ten SNPs (INRA0007631 , ALGA0011600 , ALGA0043433 , ALGA0043428 , M1GA0010535 ALGA00443338 , ALGA0087116 , MARC0056787 , ALGA0112928 , and ALGA0089047) had a relationship with the analyzed feature at a level close to significance, set at 1−5. These SNPs appear important since they are located on chromosomes on which a large number of quantitative trait loci (QTLs) and SNPs associated with reproductive characteristics, including litter size, have been identified. • Numerous piglets of hyperprolific sows generate additional costs for rearing them. • Sow hyperprolificacy decreases piglets survival rate during and after parturition. • SNP SIRI000069 have significant (p ≤ 0.05) relationship with excessive sow prolificacy. • Within this SNP sows with AA genotype are more likely to give birth to a surplus litter. • EFCAB11 gene is potentially related with litter size in sows. [ABSTRACT FROM AUTHOR]

• Reference transcriptome of the halophyte AVF was proposed. • After statistical analysis of SSRs, SNPs, and InDels, moderate polymorphism was shown. • Potential candidate genes that contributed to salt tolerance were revealed by analyzing genetic diversity combined with gene expressions. Apocyni Veneti Folium (AVF), the dried leaf of Apocynum venetum L., is a commonly used salt-tolerant Chinese medicinal herb. However, comprehensive research on the breeding of AVL varieties under salt stress has not been conducted. The purpose of this study was to identify AVF genetic variability and candidate genes conferring tolerance to salinity. Apocynum venetum L. was treated with four levels of salt stress (control, 100, 200, and 300 mM NaCl, respectively) and subjected to de novo -based RNA sequencing. Subsequently, MISA, Samtools, and Varscan programs were employed to analyze the characteristics of SSRs, SNPs, and InDels in the transcriptome sequences, respectively. The sequencing results showed that 7046 SSRs (in 54,276 unigenes) and a total of 409 repetitive motifs were found with a frequency of 12.98 %. The mainly repetitive types of SSRs were mononucleotide (49.09 %), dinucleotide (23.91 %), and trinucleotide (14.53 %); a total of 4912 SSRs with a motif length of 12–20 bp accounted for 69.17 %, indicating moderate polymorphism. At the same time, a total of 77,474 SNPs were detected, with the main type being transition (62.46 %); 114,651 InDels in 7656 unigenes were found, with a frequency of 2.03 per kb, and one locus was the most prevalent. The potential candidate genes that contributed to salt tolerance, such as c29028_g1_i1 encoding glycosyltransferase, were screened by analyzing genetic diversity combined with gene expressions. Transcriptome sequencing of AVF provides a reference for its molecular-assisted breeding to the quality identification and genetic diversity analysis. [ABSTRACT FROM AUTHOR]

Fruit color of tomato is determined by the accumulation of carotenoids which are biochemically represented as C 40 isoprenoid molecules. Tomato is a major dietary source of carotenoids like lycopene and β-carotene. In the present study, we have characterized High β-carotene content (Hbc) mutant which was identified from EMS mutagenized M 2 population of Solanum lycopersicum cv. Arka Vikas (wild-type). Wild-type and mutant fruit phenotype segregation analysis in F 2 population had shown a 3:1 (χ2 ≤ 3.84) ratio of orange and red fruit color and these results suggested that monogenic dominant mutation is responsible for orange colour fruit pigmentation in mutant. We evaluated the contents of phytoene, β-carotene and lycopene at mature green, breaker, turning, and fully (or) red ripe fruit stages in Hbc mutant and wild-type. It was found to have high β-carotene content in Hbc mutant (42.1 ± 8.82 µg/g FW) compared to wild-type (5.28 ± 2.17 µg/g FW). Effect of hbc mutation on whole transcriptome data was analyzed by microarray. This analysis has led to the identification of thousands of differentially expressed genes during fruit ripening. Gene expression pattern affected by hbc mutation, display a tendency for down-regulation rather than up-regulation. The Hbc mutant exhibits four folds up-regulation of the CYC-B gene expression and eight folds high β-carotene content at fully ripen stage. A total of three SNPs at -77, -204 and -1972 positions were identified in upstream region of the CYC-B gene, and on further segregation analysis confirms that -77 SNP was associated with orange fruit color of Hbc mutant. These results concluded that there is a close relationship between the CYC-B gene expression and orange color fruit. Characterization of Hbc mutant gives valuable information to breeders for the development of new varieties, having high β-carotene using molecular markers. [Display omitted] • Hbc mutant was identified from EMS mutagenized population of cv. Arka vikas. • Hbc mutant plants produce orange fruits, whereas cv. Arka vikas produces red color fruits. • Hbc mutant fruits accumulated 8.4 folds higher β-carotene than cv. Arka vikas. • A point mutation at −77 bp position in the CYC-B gene promoter causes overexpression of gene. [ABSTRACT FROM AUTHOR]

Cardiometabolic diseases (CMDs) are complex disorders with a heterogenous phenotype, which are caused by multiple factors including genetic factors. Single nucleotide polymorphisms (SNPs) rs45539933 (p.Ala64Thr), rs10011540 (c.-112A>C), rs3811791 (c.-1766A>G), and rs1800592 (c.-3826A>G) in the UCP1 gene have been analyzed for association with CMDs in many studies providing controversial results. However, previous studies only considered individual UCP1 SNPs and did not evaluate them in an integrated manner, which is a more powerful approach to uncover genetic component of complex diseases. This study aimed to investigate associations between UCP1 genotype combinations and CMDs or CMD risk factors in the context of non-genetic factors. We performed multiple logistic regression analysis and proposed new methodology of testing different combinations of SNP genotypes. We found that probability of CMDs increased in presence of the three-SNP combination of genotypes with minor alleles of c.-3826A>G and p.Ala64Thr and wild allele of c.-112A>C, with increasing age, body mass index (BMI), body fat percentage (BF%) and may differ between sexes and between countries. The combination of genotypes with c.-3826A>G minor allele and wild homozygotes of c.-112A>C and p.Ala64Thr was associated with increased probability of diabetes. While combination of genotypes with minor alleles of all three SNPs reduced the CMD probability. The present results suggest that age, BMI, sex, and UCP1 three-SNP combinations of genotypes significantly contribute to CMD probability. Varying of c.-112A>C alleles in the genotype combination with minor alleles of c.-3826A>G and p.Ala64Thr markedly changes CMD probability. • UCP1 rs45539933, rs10011540, and rs1800592 are not individually associated with CMDs, but are associated in combinations. • Minor alleles of three SNPs reduce CMD probability, while wild allele of rs10011540 in the combination increase the latter. • Minor allele of rs1800592 with wild alleles of rs45539933 and rs10011540 increase probability of diabetes. • Non-genetic factors – age, sex, BMI and others contribute to CMD probability together with genetic factors. • A new methodology for testing SNP genotype combinations for association with CMDs is proposed. [ABSTRACT FROM AUTHOR]

Treg cells play an important role in development of tolerance in maternal immune system against the semi-allogenic embryo. Human forkhead box protein 3 (FOXP3) gene, is the major transcription factor responsible for the regulation of Treg function during pregnancy. Single nucleotide polymorphisms (SNPs) of FOXP3 gene have been reported as a risk factor for Recurrent Pregnancy Loss (RPL), however, results from previous studies are inconsistent. We have collected data from different studies to investigate the overall association of FOXP3 SNPs with risk of RPL. PubMed, Google Scholar, Elsevier, and Cochrane databases were searched to identify eligible studies. Odds Ratio (OR) and 95 % Confidence Interval (CI), calculated via fixed effect or random effect models, were used to evaluate strength of association. This meta-analysis included 11 studies (1383 RPL cases and 1413 controls) of 6 SNPs: rs3761548 A/C, rs2232365 A/G, rs2294021 T/C, 2280883 T/C, rs5902434del/ATT and rs141704699C/T, with ≥2 studies per SNPs and at least 1 significant result. We observed that FOXP3 polymorphism was predominantly present in Asian women with history of RPL. rs2232365 A/G, rs3761548 A/C, rs2294021 T/C, rs2280883 T/C and rs5902434del/ATT polymorphisms were significantly associated with risk of RPL in Indian population. Further, among the most commonly seen polymorphism, rs3761548 A/C was significantly associated with risk of RPL in women from Kazakhstan, China and Gaza, Palestine; rs2232365 A/G in populations of Kazakhstan, Egypt, Iran and Gaza, Palestine. Results of this study indicates that FOXP3 polymorphism is significantly associated with risk of RPL, especially in Asians. • Dysregulated immune response is an important mechanism for RPL etiology. • Regulatory Tregs play a crucial role in maintenance of immune tolerance. • FOXP3 is a major transcription factor responsible for the regulation of Tregs. • Many studies were conducted in different populations on FOXP3 SNPs and RPL but he results are inconsistent. • This meta-analysis provides a comprehensive association of FOXP3 SNPs with RPL risk. • This study could be a stepping stone towards identification of an early diagnostic biomarker for RPL patients. [ABSTRACT FROM AUTHOR]

Sirtuin 5, encoded by the SIRT5 gene, is a NAD+-dependent deacylase that modulates mitochondrial metabolic processes through post-translational modifications. In this study, we aimed to examine the impact of the SIRT5 rs12216101 T>G non-coding single nucleotide polymorphism on disease severity in patients with non-alcoholic fatty liver disease (NAFLD). The rs12216101 variant was genotyped in 2,606 consecutive European patients with biopsy-proven NAFLD. Transcriptomic analysis, expression of mitochondrial complexes and oxidative stress levels were measured in liver samples from a subset of bariatric patients. Effects of SIRT5 pharmacological inhibition were evaluated in HepG2 cells exposed to excess free fatty acids. Mitochondrial energetics in vitro were investigated by high-performance liquid chromatography. In the whole cohort, the frequency distribution of SIRT5 rs12216101 TT, TG and GG genotypes was 47.0%, 42.3% and 10.7%, respectively. At multivariate logistic regression analysis adjusted for sex, age >50 years, diabetes, and PNPLA3 rs738409 status, the SIRT5 rs12216101 T>G variant was associated with the presence of non-alcoholic steatohepatitis (odds ratio 1.20, 95% CI 1.03-1.40) and F2–F4 fibrosis (odds ratio 1.18; 95% CI 1.00-1.37). Transcriptomic analysis showed that the SIRT5 rs12216101 T>G variant was associated with upregulation of transcripts involved in mitochondrial metabolic pathways, including the oxidative phosphorylation system. In patients carrying the G allele, western blot analysis confirmed an upregulation of oxidative phosphorylation complexes III, IV, V and consistently higher levels of reactive oxygen species, reactive nitrogen species and malondialdehyde, and lower ATP levels. Administration of a pharmacological SIRT5 inhibitor preserved mitochondrial energetic homeostasis in HepG2 cells, as evidenced by restored ATP/ADP, NAD+/NADH, NADP+/NADPH ratios and glutathione levels. The SIRT5 rs12216101 T>G variant, heightening SIRT5 activity, is associated with liver damage, mitochondrial dysfunction, and oxidative stress in patients with NAFLD. In this study we discovered that the SIRT5 rs12216101 T>G variant is associated with higher disease severity in patients with non-alcoholic fatty liver disease (NAFLD). This risk variant leads to a SIRT5 gain-of-function, enhancing mitochondrial oxidative phosphorylation and thus leading to oxidative stress. SIRT5 may represent a novel disease modulator in NAFLD. [Display omitted] • Mitochondrial dysfunction plays a key role in NAFLD onset and progression. • SIRT5 is crucial in the regulation of mitochondrial processes. • SIRT5 rs12216101 T>G SNP associates with higher disease severity in patients with NAFLD. • SIRT5 rs12216101 T>G variant induces upregulation of OXPHOS in patients with NAFLD. • SIRT5 rs12216101 T>G variant promotes oxidative stress in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Several two-sample Mendelian randomization studies have reported discordant results concerning the association between grip strength and cardiovascular disease, possibly due to the number of instrumental variables used, pleiotropic bias, and/ or effect modification by age and sex. We conducted a sex- and age-stratified one-sample Mendelian randomization study in the Canadian Longitudinal Study on Aging. We investigated whether grip strength is associated with carotid intima media thickness (cIMT), a marker of vascular atherosclerosis event risk, using eighteen single nucleotide polymorphisms (SNP) identified as specifically associated with grip strength. A total of 20,258 participants of self-reported European ancestry were included in the analytic sample. Our Mendelian randomization findings suggest a statistically significant association between grip strength and cIMT (MR coefficient of 0.02 (95% CI: 0.01, 0.04)). We found no statistically significant differences between sexes (p-value = 0.201), or age groups [(≤ 60 years old versus >60 years old); p-value = 0.421]. This study provides evidence that grip strength is inversely associated with cIMT. Our one-sample MR study design allowed us to demonstrate that there is no evidence of heterogeneity of effects according to age group or biological sex. [ABSTRACT FROM AUTHOR]

The majority of drugs are metabolized by cytochrome P450 (CYP) enzymes, primarily belonging to the CYP1, CYP2 and CYP3 families. Genetic variations are the main cause of inter-individual differences in drug response, which constitutes a major concern in pharmacotherapy. G-quadruplexes (G4s), are non-canonical DNA and RNA secondary structures formed by guanine-rich sequences. G4s have been implicated in cancer and gene regulation. In this study, we investigated putative G4-forming sequences (PQSs) in the CYP genes. Our findings reveal a high density of PQSs in the full genes of CYP family 2. Moreover, we observe an increased density of PQSs in the promoters of CYP family 1 genes compared to non-CYP450 genes. Importantly, stable PQSs were also identified in all studied CYP genes. Subsequently, we assessed the impact of the most frequently reported genetic mutations in the selected genes and the possible effect of these mutations on G4 formation as well as on the thermodynamic stability of predicted G4s. We found that 4 SNPs overlap G4 sequences and lead to mutated DNA and RNA G4 forming sequences in their context. Notably, the mutation in the CYP2C9 gene, which is associated with impaired (S)-warfarin metabolism in patients, alters a G4 sequence. We then demonstrated that at least 10 of the 13 chosen cytochrome P450 G4 candidates form G-quadruplex structures in vitro , using a combination of spectroscopic methods. In conclusion, our findings indicate the potential role of G-quadruplexes in the regulation of cytochrome genes, and emphasize the importance of G-quadruplexes in drug metabolism. • G-quadruplexes (G4s) can influence drug response by modulating CYP gene expression. • G4-forming sequences are enriched in CYP family 2 genes. • Some SNPs are located within PQSs or in their immediate vicinity; one non-overlapping mutation changed the DNA G4 sequence. • Cytochrome P450 enzymes-associated mutations may affect DNA and/or RNA G4 formation and stability in CYP genes. [ABSTRACT FROM AUTHOR]

ETS1, an important member of the ETS transcription factor family, is involved in a variety of physiological processes in living organisms, such as cell development, differentiation, proliferation and apoptosis, and is thought to be associated with embryonic development and reproduction. However, the polymorphism of ETS1 has been rarely studied, and its potential impact on the formation of reproductive traits in sheep remains unclear. Here, we first analyzed polymorphisms of ETS1 in a population of 382 small-tailed Han sheep with a lambing number record using the Kompetitive Allele Specific PCR (KASP) technique. The results showed the presence of a SNP locus rs161611767 (T > C) in the 3′UTR of ETS1. The association analysis showed the lambing number of first, second and third parity in the individuals with the CC genotype (2.51 ± 0.108, 2.51 ± 0.179, 1.27 ± 0.196) was higher than that of individuals with the TT genotype (1.79 ± 0.086, 1.56 ± 0.102, 0.56 ± 0.100) (P < 0.05). Then, molecular biotechnologies were used to investigate the effects of the EST1 rs161611767 mutant locus on host gene expression in sheep and the underlying mechanism of its effect on sheep reproduction. The RT‒qPCR results showed that the expression of ETS1 was higher in individuals with the CC genotype than in those with the TT genotype (P < 0.05). The dual luciferase reporter assay showed that the luciferase activity of ETS1 in sheep with the TT genotype was decreased compared to CC genotype (P < 0.05), confirming the existence of EST1 rs161611767 in the 3′UTR as a functional SNP. Given that the 3′UTR is an important regulatory region of gene transcription and translation, we performed bioinformatics prediction and confirmed that the SNP rs161611767 of ETS1 was a direct functional target of miR-216a-3p using dual luciferase activity assay, and the binding capacity of allele T was stronger than that of allele C. Subsequently, the cell transfection results showed that miR-216a-3p suppressed the endogenous expression of ETS1 in sheep primary granulosa cells (GCs). Finally, CCK-8, EdU, WB detection of marker proteins and flow cytometry were used to detect the effects of miR-216a-3p on GCs viability and proliferation/apoptosis, respectively. The results showed that miR-216a-3p inhibited the proliferation of GCs while promoting apoptosis of GCs. In conclusion, these results demonstrate that the SNP rs161611767 of ETS1 is associated with lambing number in small-tailed Han sheep, and miR-216a-3p can act as a regulatory element binding to the T mutation in rs161611767 to regulate ETS1 expression and affect GCs development, which may indirectly affect the number of lambs in sheep. These studies provide evidence for the involvement of ETS1 polymorphisms in sheep reproduction and are expected to provide new insights to elucidate the molecular genetic mechanisms of lambing traits in sheep. • ETS1 SNP rs161611767 (T > C) was associated with the number of lambs produced in sheep. • The expression of ETS1 with the rs161611767 allele T was decreased than that with C allele. • The presence of SNP rs161611767 allele T promoted apoptosis of sheep granulosa cells. • miR-216a-3p interacted with SNP rs161611767 allele T to promote apoptosis of sheep granulosa cell. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2 , HFF1A , ILI8R1 , EIF2AK2 , TXNRD2 , PPARA , NDUFS2 and ERN1. Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them. [Display omitted] • Oxidative stress (OS) is an intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. • Hyperglycemia contribute to increased reactive oxygen species (ROS) generation and ROS can lead to insulin resistance. • Many genetic systems have been related to OS and T2D development • Studied SNPs and haplotypes are associated with OS. Their interaction with OS contribute to T2D in spanish population. [ABSTRACT FROM AUTHOR]

The majority of human mRNAs generate alternative 3′ untranslated regions (UTRs) through various processes, including RNA modifications such as RNA editing, m6A methylation, and alternative polyadenylation (APA), with 3′UTR splicing as an emerging mechanism. Multiple factors, ranging from the genome to transcriptome level, regulate these processes and contribute to 3′UTR heterogeneity. Genomic variants in 3′UTR regions as well as aberrant 3′UTR processing alter the transcriptomic landscape and are associated with cancer. Increasing evidence, aided by high-resolution sequencing technologies and large-scale computational analyses, points towards potential crosstalk between these processes, whose deregulation may further contribute to cancer pathogenesis. In-depth characterization of these events will increase our appreciation of their significance and help to drive therapeutic development in this field. Alternative 3′ untranslated regions (3′UTRs) are widespread and increase transcriptome diversity. Genomic variations in 3′UTRs can disrupt regulatory elements, including microRNA binding sites, poly(A) signals, and m6A sites, leading to aberrant 3′UTR processing. Comprehensive analyses of 3′UTR-related quantitative trait loci (QTLs), such as RNA editing QTLs (edQTLs) and 3′ APA QTLs (3′aQTLs), have found that many are dysregulated in cancer and are associated with overall patient survival and drug response. 3′UTR splicing is widespread and upregulated in cancer, and represents an emerging mechanism that contributes to 3′UTR heterogeneity and tumorigenesis. Crosstalk among the 3′UTR modification and processing steps may serve as an added layer of regulation to further fine-tune gene expression. [ABSTRACT FROM AUTHOR]

Lactose intolerance is a type of digestive problem that may threaten the population because milk and dairy products compose of nutrients that are essential for human body. Genetic tests possess a great potential to detect lactose intolerance as it can be used in children and even infants. However, a new approach to analyze the genetic test results is needed to elucidate the Single Nucleotide Polymorphisms (SNPs) that are related to lactose intolerance. In this work, we utilized the machine learning based feature selection to select the SNPs associated with lactose tolerance trait from genotyping samples of direct-to-customer (DTCG genetic tests, obtained from the public database. Recursive Feature Elimination (RFE) with XGBoost model was used to perform feature selection. We also compared three different models, such as XGBoost, support vector machine (SVM), and random forest (RF) for training the selected features. Our findings revealed that 20 SNPs (out of 3501) were chosen, with rs4394668 as the most important variables (F-score 0.009). Furthermore, when compared to the RF and SVM models, the XGBoost model had the highest accuracy (0.87). Further studies should be undertaken to elucidate how the selected SNPs may lead to the lactose intolerance trait. [ABSTRACT FROM AUTHOR]

Les nodopathies auto-immunes (NA) sont des pathologies démyélinisantes du système nerveux périphérique qui ont la particularité d'avoir une physiopathologie médiée par des anticorps majoritairement d'isotype IgG4. La présence de ces anticorps, l'installation aiguë ou subaiguë de la neuropathie, la mauvaise réponse aux immunoglobulines intraveineuses et la bonne sensibilité au rituximab (anticorps monoclonal thérapeutique anti-CD20) ont récemment conduit à exclure les NA du groupe des polyradiculoneuropathies inflammatoires démyélinisantes chroniques. À ce jour, quatre auto-anticorps ciblant des protéines axo-gliales au niveau des nœuds de Ranvier et des paranœuds ont été identifiés : les anti-pan-neurofascine (anti-pan-Nfasc) qui reconnaissent toutes les isoformes de neurofascine, les anti-neurofascine 155 (anti-Nfasc155), les anti-contactine 1 (anti-CNTN1) et les anti- contactin associated protein 1 (anti-CASPR1). Actuellement en France, l'identification biologique de ces anticorps s'effectue en cytométrie en flux sur cellules transfectées HEK dans le laboratoire d'immunologie de l'AP-HM, à l'Hôpital La Conception à Marseille. Les NA engagent le pronostic fonctionnel et parfois même le pronostic vital. Leur diagnostic doit donc être le plus rapide possible pour de ne pas retarder la prise en charge thérapeutique. Autoimmune nodopathy (AN) are demyelinating pathologies of the peripheral nervous system which have the particularity of having a pathophysiology mediated by antibodies mainly of IgG4 isotype. Specific autoantibodies, the acute or subacute onset of neuropathy, the poor response to intravenous immunoglobulins and the improvement after rituximab led to exclude AN from the group of chronic inflammatory demyelinating polyradiculoneuropathies. Currently, 4 auto-antibodies targeting axo-glial proteins at the nodes of Ranvier and paranodes have been identified: anti-pan-neurofascin (anti-pan-Nfasc) antibodies which recognize all neurofascin isoforms, anti-neurofascin 155 (anti-Nfasc155), anti-contactin 1 (anti-CNTNI) and anti-contactin associated protein 1 (anti-CASPRI). Currently, in France, the identification of these antibodies is processed by flow cytometry on transfected HEK cells in the Immunology laboratory at the hospital La Conception in Marseille. As AN can cause severe disability and sometimes be life-threatening, their diagnosis should be done as soon as possible in order to start promptly the treatment. [ABSTRACT FROM AUTHOR]

The effectiveness of metronidazole against the tetraploid intestinal parasite Giardia lamblia is dependent on its activation/inactivation within the cytoplasm. There are several activating enzymes, including pyruvate ferredoxin reductase (PFOR) and nitroreductase (NR) 1 which metabolize metronidazole into toxic forms, while NR2 on the other hand inactivates it. Metronidazole treatment failures have been increasing rapidly over the last decade, indicating genetic resistance mechanisms. Analyzing genetic variation in the PFOR and NR genes in susceptible and refractory Giardia isolates may help identify potential markers of resistance. Full length PFOR1 , PFOR2 , NR1 and NR2 genes from clinical culturable isolates and non-cultured clinical Giardia assemblage B samples were cloned, sequenced and single nucleotide variants (SNVs) were analyzed to assess genetic diversity and alleles. A similar ratio of amino acid changing SNVs per gene length was found for the NRs; 4.2% for NR1 and 6.4% for NR2 , while the PFOR1 and PFOR2 genes had less variability with a ratio of 1.1% and 1.6%, respectively. One of the samples from a refractory case had a nonsense mutation which caused a truncated NR1 gene in one out of six alleles. Further, we found three NR2 alleles with frameshift mutations, possibly causing a truncated protein in two susceptible isolates. One of these isolates was homozygous for the affected NR2 allele. Three nsSNVs with potential for affecting protein function were found in the ferredoxin domain of the PFOR2 gene. The considerable variation and discovery of mutations possibly causing dysfunctional NR proteins in clinical Giardia assemblage B isolates, reveal a potential for genetic link to metronidazole susceptibility and resistance. [Display omitted] • Mutations in ferredoxin domains of thr nitroreductases and pyruvate ferredoxin oxidoreductases may alter protein function. • Nonsense mutation in nitroreductase 1 alleles may contribute towards metronidazole tolerance in Giardia. • Susceptible Giardia isolates had frameshift mutations in nitroreductase 2 alleles, possibly affecting metronidazole toxicity. [ABSTRACT FROM AUTHOR]

Salinity is a serious environmental problem that limits plant yield in almost half of the agricultural fields. The hitomebore salt tolerant 1(hst1) is a mutant B-type response regulator gene that was reported to improve salinity tolerance in the 'YNU31-2-4' (YNU) genotype. The sister line (SL) is salt-sensitive, and the nearest genomic relative of the YNU plant has the OsRR22 gene, which is the non-mutant form of the hst1 gene. Biochemical and comprehensive transcriptome analysis of SL and YNU plants was performed to clarify the salinity tolerance mechanism(s) mediated by the hst1 gene. The hst1 gene reduced Na+ ions, lipid peroxidation, and H 2 O 2 content, and improve proline and antioxidant enzymes activities under salt stress. Various transporter and gene-specific transcriptional regulator genes up-regulated in presence of the hst1 gene under saline conditions, identifying that post-stress transcription factors (OsbHLH056 , OsH43 , OsGRAS29, and OsMADS1) contributed to improved salinity tolerance in YNU plants. Specifically, OsSalT , miR156 , and OsLPT1.16 genes were up-regulated, while upstream (OsHK s and OsHP s) and downstream regulators of the OsRR22 gene were down-regulated in YNU plants under saline conditions. Notably, the transcription factors reprogramming, upstream and downstream genes, indicate that these pathways are transcriptionally regulated by the hst1 gene. The findings of the regulatory role of the hst1 gene on plant transcriptome provide a greater understanding of hst1 –mediated salt tolerance in rice plants. This knowledge will contribute to understanding the salinity tolerance mechanisms in rice and the evolution of salt-tolerant crops with the ability to withstand higher salinity to ensure food security during climate change. • The hst1 reduced ion accumulation and ROS production. • The hst1 improve antioxidant osmoprodectant production and enzyme activity. • The hst1 provides salinity tolerance by reprogramming transcription factors in rice. [ABSTRACT FROM AUTHOR]

In euryhaline fish frequently exposed to salinity shifts, epigenetic mechanisms are expected to play a crucial role in facilitating adaptation. Nile tilapia Oreochromis niloticus is recognized for its rapid growth and adaptability to low-salinity environments. The GIFT strain of the tilapia is suggested to be a good candidate for culture in brackish water. Recently, the mechanisms underlying salinity challenge in tilapia have received increasing attention. In this study, the dynamics of DNA methylation in the skin tissue of GIFT tilapia in response to high salinity stress were explored by integrating whole-genome bisulfite sequencing (WGBS) with published transcriptomic and genetic data. DNA methylation was enriched in heterochromatin and correlated positively with the density of transposable elements (TEs). A notable increase in CpG methylation level was detected, especially in the body of TEs, possibly due to the downregulated expression of DNA demethylases. Among the 10,514 differentially methylated regions (DMRs), 6346 showed hypermethylation, and 4168 displayed hypomethylation, with a marked prevalence on the chromosome LG3. Integration of methylation data with the skin transcriptome data unveiled a significant negative correlation (p < 0.05) between methylation levels in promoter regions and gene expression. Colocalization of differentially expressed genes (DEGs) and differentially methylated promoters (DMPs) identified 69 candidate genes. Additionally, 17 DMRs were overlapped with or near to the 24 SNPs on chromosome LG18:24,543,912 to 29,002,006 that significantly associated with salinity tolerance, highlighting candidate genes like mtcl1 , nfatc4 , pex19 , kirrel1b , acot4 , and pard3ab acting in adaption to high salinity. The methylation differences and expression changes of the candidate gene acot4 under high salinity stress were confirmed through BS-PCR and qRT-PCR. This investigation offers novel gene resources for further functional study on tilapia's adaptation to salinity changes from the genetic and epigenetic perspectives. • DNA methylation was correlated positively with the density of transposable elements. • A significant negative correlation was detected between methylation levels in promoter regions and gene expression. • The methylation and expression changes of the gene acot4 in response to salinity stress. [ABSTRACT FROM AUTHOR]

Genomic prediction utilizes relationships between phenotypes and thousands of genetic markers dispersed across the genome of a species under selection to estimate an individual's breeding value. Viral hemorrhagic septicemia (VHS) is a devastating disease that causes high mortality in the olive flounder (Paralichthys olivaceus). Selection of VHS resistant individuals using traditional pedigree-based approaches is slow and ineffective; therefore, we investigated the potential of genomic selection to identify superior VHS-resistant individuals. In this study, various statistical models and algorithms, including the multilayer perceptron (MLP) and convolutional neural network (CNN), were compared for their prediction accuracy of breeding values. Other models assessed include pedigree-based best linear unbiased prediction (PBLUP), genomic best linear unbiased prediction (GBLUP), Bayesian A (BA), Bayesian B (BB), Bayesian C (BC), Bayesian Lasso (BL), Bayesian ridge regression (BRR), elastic net (EN), ridge regression (RR), and random forest (RF). These models were assessed for their ability to predict VHS resistance based on genomic data obtained from high-quality 70 K single nucleotide polymorphism (SNP) Affymetrix® Axiom® myDesign™ Genotyping Array from 865 animals. Furthermore, we investigated the population structure of the selected flounder population using a genomic relatedness matrix, PCA analysis, kinship coefficients, and multidimensional scaling. The results revealed that RF had the highest prediction accuracy for the three VHS-resistance traits (binary survival, days to death, and time of death), followed by BRR and GBLUP. PBLUP exhibits the lowest accuracy for these traits. Machine learning (ML) models, such as RF, outperformed traditional PBLUP and GBLUP, showing the greatest improvement over other Bayesian methods (BA, BB, and BC). The optimal parameters were determined for the best models, including specific marker sizes and sample size recommendations. The selected models and their parameters significantly improved the prediction of VHS resistance, demonstrating the potential of genomic selection to outperform the traditional pedigree-based methods. Our findings indicate that genomic selection can be more effective using ML models than conventional approaches in predicting VHS resistance and offers a means to enhance the genetic resistance of olive flounder in aquaculture to this disease. • Identifying disease resistance traits are necessary for breeding programs to create better animals. • A 70 K high density SNP array was used in the genomic prediction for VHSV traits. • The prediction accuracy ranged from 0.53 to 0.69 (lowest for PBLUP and highest for RF and CNN) • Machine learning models outperformed traditional PBLUP, GBLUP, and Bayesian models. • Increasing marker and population numbers also increase the genomic prediction ability. [ABSTRACT FROM AUTHOR]