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Head and neck cancer is the seventh leading cancer diagnosis worldwide. One of the most common cancers in the head and neck region is laryngeal cancer. In past years, the incidence of laryngeal squamous cell carcinoma has risen by 23%, and despite progress in treatment modalities, the survival rate has not changed. It is well known that genetic alterations may contribute to individuals' susceptibility to cancer. Research of genetic alterations, such as single nucleotide polymorphisms, is essential to understanding carcinogenesis and susceptibility of laryngeal squamous cell carcinoma. A total of 200 LSCC patients and 200 controls were included in this retrospective case-control study; both groups were matched by age and sex. In the present study, we analyzed six SNPs in genes essential for apoptosis regulation: TP53 (rs9895829, rs17884306), BCL2 (rs1564483, rs4987855), BAX (rs704243), NOXA (PMAIP1) (rs1041978, rs78800940). We evaluated their associations with the risk of LSCC development, its pathomorphological manifestation, and patients' overall survival rate. Genotyping was carried out using RT-PCR. The AG genotype of rs9895829 was more prevalent in controls than in cancer patients, leading to lower susceptibility to LSCC (OR = 0.301; 95%CI 0.096–0.940; p = 0.039). None of the analyzed SNPs showed an association with pathomorphological features of LSCC, but NOXA rs1041978 T allele carriers were found to be diagnosed with LSCC at an older age (OR = 1.962; 95%CI 1.072–3.592; p = 0.031). There was no statistically significant association between investigated SNPs and patient OS. The present study indicates that the AG genotype of rs9895829 provides a protective effect against LSCC development. [ABSTRACT FROM AUTHOR]

This study utilized 303 pepper accessions from diverse Capsicum species to explore fruit traits, including length, width, wall thickness, and weight. Descriptive statistics revealed a mean fruit length of 66.19 mm, width of 23.48 mm, wall thickness of 1.89 mm, and weight of 15.29 g, with significant variability, particularly in fruit weight. Correlation analysis demonstrated strong positive relationships between fruit width, weight, and fruit wall thickness (r = 0.89 and r = 0.86, respectively), while fruit length showed weaker correlations with these traits. Analysis of fruit positions revealed that the majority of accessions had a pendent fruit position (156), followed by erect (85) and intermediate (8). In terms of fruit shape, triangular and narrow triangular shapes were the most common, observed in 102 and 98 accessions, respectively. Genome-wide association studies (GWAS) identified significant single nucleotide polymorphisms (SNPs) associated with fruit traits across four models (Blink, FarmCPU, MLM, MLMM). The number of significantly associated SNPs were as follows: fruit length (89), fruit width (55), fruit weight (63), fruit wall thickness (48), fruit shape (151), and fruit position (51). Several genes were also identified where the SNPs are located or adjacent to, providing candidate genes for further exploration of the genetic basis of fruit morphology. Notably, genes such as E3 ubiquitin-protein ligase RGLG1 (associated with fruit width), Homeobox-leucine zipper protein HDG11 (involved in fruit width), Auxin response factor 23 (linked to fruit shape), and ATP-dependent zinc metalloprotease FtsH (related to fruit weight) were identified. These findings enhance our understanding of the genetic basis of fruit morphology in Capsicum, offering valuable insights for breeding and agricultural practices. [ABSTRACT FROM AUTHOR]

Sweet potato (Ipomoea batatas) is an important food crop that plays a pivotal role in preserving worldwide food security. Due to its polyploid genome, high heterogeneity, and phenotypic plasticity, sweet potato genetic characterization and breeding is challenging. Genome-wide association studies (GWASs) can provide important resources for breeders to improve breeding efficiency and effectiveness. GWASpoly was used to identify 28 single nucleotide polymorphisms (SNPs), comprising 21 unique genetic loci, associated with sweet potato storage root traits including dry matter (4 loci), subjective flesh color (5 loci), flesh hue angle (3 loci), and subjective skin color and skin hue angle (9 loci), in 384 accessions from the USDA sweet potato germplasm collection. The I. batatas 'Beauregard' and I. trifida reference genomes were utilized to identify candidate genes located within 100 kb from the SNPs that may affect the storage traits of dry matter, flesh color, and skin color. These candidate genes include transcription factors (especially Myb, bHLH, and WRKY family members), metabolite transporters, and metabolic enzymes and associated proteins involved in starch, carotenoid, and anthocyanin synthesis. A greater understanding of the genetic loci underlying sweet potato storage root traits will enable marker-assisted breeding of new varieties with desired traits. This study not only reinforces previous research findings on genes associated with dry matter and β-carotene content but also introduces novel genetic loci linked to these traits as well as other root characteristics. [ABSTRACT FROM AUTHOR]

The Ningxiang pig, one of the well-known Chinese native pig breeds, has the advantages of tender meat, high intramuscular fat (IMF) content, and roughage tolerance, compared to the commercial lean pig breeds. The genetic basis for complex traits in Ningxiang pigs has been previously studied through other genetic markers, such as Single Nucleotide Polymorphism (SNP), while the characteristics of copy number variation (CNV) and the selection signal have not been investigated yet. In this study, GGP 50 k genotyping data of 2242 Ningxiang pigs (NX) and 1137 Duroc pigs (Duroc) were involved in CNV atlas construction and selection signals identification. Annotations of genes and quantitative trait locus (QTLs) were performed on the target candidate regions, as follows: (1) 162 CNVs were detected in Ningxiang pigs, while 326 CNVs were detected in Duroc pigs, and there are 21 copy number variation regions (CNVRs) shared between them; (2) The CNVRs of Duroc are more abundant, with 192 CNVRs, accounting for 1.61% of the entire genome, while those of Ningxiang pigs only have 98 CNVRs, accounting for 0.49%; (3) The QTLs annotated on CNVs and selected regions of Ningxiang pigs were mainly associated with meat quality and fertility. In contrast, the Duroc QTLs' notes relate primarily to the carcass and immunity, and explain why they have a higher slaughter rate and immunity; (4) There is a presence of high-frequency acquired CNVs, specifically in Ningxiang pigs, with 24 genes significantly enriched in the sensory receptor-related pathway in this region; (5) Based on the CNVs atlas, candidate genes such as 3 inositol 1,4,5-triphosphate receptor, type 3 (ITPR3), forkhead box protein K2 (FOXK2), G-protein coupled estrogen receptor 1 (GPER1), Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase 1 (TPI1), and other candidate genes related to fat deposition and differentiation were screened. In general, this study improved our knowledge about copy number variation and selection signal information of Ningxiang pigs, which can not only further explain the genetic differences between Chinese native and Western commercial pig breeds, but also provide new materials for the analysis of the genetic basis of complex traits. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed. [ABSTRACT FROM AUTHOR]

Beyond the essential role of p27Kip1 and cyclin D2 in cell cycle progression, they are also shown to confer an anti-apoptotic function in peripheral blood (PB) lymphocytes. Although the aberrant longevity and expression of p27Kip1 and cyclin D2 in leukemic cells is well documented, the exact mechanisms responsible for this phenomenon have yet to be elucidated. This study was undertaken to determine the associations between polymorphisms in the CDKN1B and CCND2 genes (encoding p27Kip1 and cyclin D2, respectively) and susceptibility to chronic lymphocytic leukemia (CLL), as well as their influence on the expression of both cell cycle regulators in PB leukemic B cells and non-malignant T cells from untreated CLL patients divided according to the genetic determinants studied. Three CDKN1B single-nucleotide polymorphisms (SNPs), rs36228499, rs34330, and rs2066827, and three CCND2 SNPs, rs3217933, rs3217901, and rs3217810, were genotyped using a real-time PCR system. The expression of p27Kip1 and cyclin D2 proteins in both leukemic B cells and non-malignant T cells was determined using flow cytometry. We found that the rs36228499A and rs34330T alleles in CDKN1B and the rs3217810T allele in the CCND2 gene were more frequent in patients and were associated with increased CLL risk. Moreover, we observed that patients possessing the CCND2rs3217901G allele had lower susceptibility to CLL (most pronounced in the AG genotype). We also noticed that the presence of the CDKN1Brs36228499CC, CDKN1Brs34330CC, CDKN1Brs2066827TT, and CCND2rs3217901AG genotypes shortened the time to CLL progression. Statistically significant functional relationships were limited to T cells and assigned to CDKN1B polymorphic variants; carriers of the polymorphisms rs34330CC and rs36228499CC (determining the aggressive course of CLL) expressed a decrease in p27Kip1 and cyclin D2 levels, respectively. We indicate for the first time that genetic variants at the CDKN1B and CCND2 loci may be considered as a potentially low-penetrating risk factor for CLL and determining the clinical outcome. [ABSTRACT FROM AUTHOR]

The advent of recycling antibodies, leveraging pH-dependent antigen binding and optimized FcRn interaction, has advanced the field of antibody therapies, enabling extended durability and reduced dosages. Eculizumab (Soliris®) demonstrated the efficacy of C5 inhibitors for paroxysmal nocturnal hemoglobinuria (PNH), while its derivative, ravulizumab (Ultomiris®), recognized as a recycling antibody, extended the dosing intervals. However, limitations including intravenous administration and inefficacy in patients with the R885H single-nucleotide polymorphism (SNP) in C5 could necessitate alternative solutions. Crovalimab (PiaSky®), a next-generation recycling antibody, overcomes these challenges with innovative charge engineering, achieving the enhanced cellular uptake of C5–crovalimab complexes and targeting a unique C5 epitope, allowing for efficacy regardless of the R885H SNP. This study highlights crovalimab's distinctive molecular features, showing its eliminated binding to Fcγ receptors and C1q, alongside its optimized antigen binding characteristics. The impact of charge engineering was reconfirmed in mice, demonstrating faster C5 clearance than recycling antibodies. Notably, in the maintenance dosing regimen, crovalimab neutralizes approximately seven C5 molecules per antibody on average. Furthermore, its design also reduces the viscosity to facilitate high-concentration formulations suitable for subcutaneous delivery. Consequently, crovalimab offers a four-weekly subcutaneous injection regimen for PNH, marking a substantial improvement in treatment convenience and potentially transforming patients' quality of life. [ABSTRACT FROM AUTHOR]

This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene–environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents. Our analysis revealed 37 single-nucleotide variants from 36 candidate genes and over 200 CGG repeats in the FMR1 gene in one subject. The identified variants were classified as uncertain, likely pathogenic, or pathogenic based on in-silico algorithms and ACMG criteria. Notably, 52% of the identified variants were homozygous, indicating a recessive genetic architecture to ASD in this population. This finding underscores the significant impact of high consanguinity within the Qatari population, which could be utilized in genetic counseling/screening program in Qatar. We also discovered single nucleotide variants in 13 novel genes not previously associated with ASD: ARSF, BAHD1, CHST7, CUL2, FRMPD3, KCNC4, LFNG, RGS4, RNF133, SCRN2, SLC12A8, USP24, and ZNF746. Our investigation categorized the candidate genes into seven groups, highlighting their roles in cognitive development, including the ubiquitin pathway, transcription factors, solute carriers, kinases, glutamate receptors, chromatin remodelers, and ion channels. [ABSTRACT FROM AUTHOR]

Oil tea camellia (Camellia spp.) is an important woody oil crop with a high nutritional and economic value. Whole-genome resequencing (WGR) technology can provide an in-depth understanding of the genetic background of this plant as well as a reference for breeding research, germplasm resource conservation, and genetic modification. In this study, we analyzed SNP and InDel variations in 49 individual oil tea camellia germplasm samples collected from five populations located in three provinces of China: Hainan, Guangdong and Guangxi. The samples were analyzed through WGR after the ploidy of the samples was determined through flow cytometry. A total of 239,441,603 high-quality single nucleotide polymorphisms (SNPs) and 23,510,374 high-quality insertion/deletion variation sites (InDels) were obtained. The distribution of SNPs and InDels in different functional regions differed significantly, with a high density of variations in non-coding regions, such as intergenic regions and introns, and a relatively low density of variations in coding regions. Transition was the main type of SNP variation. A population genetic diversity analysis revealed that the sampled oil tea camellia populations exhibited a high genetic diversity and extensive genetic variation. The genetic diversity of the oil tea camellia populations in the Hainan region was higher than inland regions. This study also determined the genetic diversity of and variations between octoploid and decaploid oil tea camellia in the tropics and between Hainan-based and inland oil tea camellia. Such findings provide a reference for the conservation of germplasm resources and the genetic modification of oil tea camellia. [ABSTRACT FROM AUTHOR]

Understanding the genetic basis of sweet taste preference is crucial for potential implications in diet-related health outcomes, such as obesity. This study identified genes and single nucleotide polymorphisms (SNPs) associated with sweet taste preferences over time. Data from the American Nurses' Health Study (NHS1) and Health Professionals Follow-up Study (HPFS) cohorts were analyzed. Using tools like PLINK and METAL for genetic associations and FUMA for functional annotation, the study identified eight SNPs associated with sweet taste preferences. Notably, rs80115239 and rs12878143 were identified as key determinants of the highest and lowest associations with sweet taste preferences, respectively. Individuals with the rs80115239 (AA) genotype displayed a higher preference for sweet tastes, including chocolate and cake, but a lower preference for physical activity, fruits, and vegetables, particularly in females from the NHS1 cohort, linking this genotype to a higher obesity risk. Conversely, those with the rs12878143 (CC) genotype preferred fruits, vegetables, coffee, and tea, with a lower preference for sweetened beverages, but the correlation with obesity risk was less clear due to inconsistent data. In conclusion, these findings highlight the genetic influences on sweet taste preference and their potential role in personalized dietary recommendations and obesity management strategies. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is the most common modification in eukaryotic RNAs. Growing research indicates that m6A methylation is crucial for a multitude of biological processes. However, research on the m6A modifications in the regulation of porcine muscle growth is lacking. In this study, we identified differentially expressed genes in the neonatal period of muscle development between Large White (LW) and NingXiang (NX) pigs and further reported m6A methylation patterns via MeRIP-seq. We found that m6A modification regulates muscle cell development, myofibrils, cell cycle, and phosphatase regulator activity during the neonatal phase of muscle development. Interestingly, differentially expressed genes in LW and NX pigs were mainly enriched in pathways involved in protein synthesis. Furthermore, we performed a conjoint analysis of MeRIP-seq and RNA-seq data and identified 27 differentially expressed and m6A-modified genes. Notably, a typical muscle-specific envelope transmembrane protein, WFS1, was differentially regulated by m6A modifications in LW and NX pigs. We further revealed that the m6A modification accelerated the degradation of WFS1 in a YTHDF2-dependent manner. Noteworthy, we identified a single nucleotide polymorphism (C21551T) within the last exon of WFS1 that resulted in variable m6A methylation, contributing to the differing WFS1 expression levels observed in LW and NX pigs. Our study conducted a comprehensive analysis of the m6A modification on NX and LW pigs during the neonatal period of muscle development, and elucidated the mechanism by which m6A regulates the differential expression of WFS1 in the two breeds. [ABSTRACT FROM AUTHOR]

Simple Summary: Fish farming provides an efficient means of obtaining high-quality protein for humans. However, the decreased growth rate of aquaculture fish due to germplasm degradation often increases production costs and reduces economic benefits. Therefore, it is particularly important to develop fast-growing varieties and elucidate the genetic mechanisms underlying growth traits. In this study, we identified 50 growth-related markers in the genome of Lateolabrax maculatus, an important marine aquaculture species, with the phenotypic variance explained up to 15.82%, which will help in marker-assisted breeding for fast-growing varieties. Additionally, 47 growth-related candidate genes were annotated, and the functions of some of these genes in growth traits have been confirmed in mice or zebrafish through gene knockout or knockdown experiments. The 47 candidate genes are mainly associated with the metabolism of energy, glucose, and lipids and the development of musculoskeletal and nervous systems, which may act as drivers for the growth of L. maculatus. Altogether, our study identified growth-related markers and candidate genes, which will help develop the fast-growing varieties of L. maculatus and elucidate genetic mechanisms underlying its growth traits. Spotted sea bass (Lateolabrax maculatus) is an important marine economic fish in China, ranking third in annual production among marine fish. However, a declined growth rate caused by germplasm degradation has severely increased production costs and reduced economic benefits. There is an urgent need to develop the fast-growing varieties of L. maculatus and elucidate the genetic mechanisms underlying growth traits. Here, whole-genome resequencing technology combined with extreme phenotype genome-wide association analysis (XP-GWAS) was used to identify candidate markers and genes associated with growth traits in L. maculatus. Two groups of L. maculatus, consisting of 100 fast-growing and 100 slow-growing individuals with significant differences in body weight, body length, and carcass weight, underwent whole-genome resequencing. A total of 4,528,936 high-quality single nucleotide polymorphisms (SNPs) were used for XP-GWAS. These SNPs were evenly distributed across all chromosomes without large gaps, and the average distance between SNPs was only 175.8 bp. XP-GWAS based on the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (Blink) and Fixed and random model Circulating Probability Unification (FarmCPU) identified 50 growth-related markers, of which 17 were related to body length, 19 to body weight, and 23 to carcass weight. The highest phenotypic variance explained (PVE) reached 15.82%. Furthermore, significant differences were observed in body weight, body length, and carcass weight among individuals with different genotypes. For example, there were highly significant differences in body weight among individuals with different genotypes for four SNPs located on chromosome 16: chr16:13133726, chr16:13209537, chr16:14468078, and chr16:18537358. Additionally, 47 growth-associated genes were annotated. These genes are mainly related to the metabolism of energy, glucose, and lipids and the development of musculoskeletal and nervous systems, which may regulate the growth of L. maculatus. Our study identified growth-related markers and candidate genes, which will help to develop the fast-growing varieties of L. maculatus through marker-assisted breeding and elucidate the genetic mechanisms underlying the growth traits. [ABSTRACT FROM AUTHOR]

Simple Summary: This study reports an unusual case of hermaphroditism in Japanese flounder captured from the Bohai Sea. In this study, the results showed that the heterozygosity of the intersex Japanese flounder was 0.632, with the synchronous maturation of the testis and ovary, and eggs and the sperm were capable of fertilization. The levels of reproduction-related hormones were intermediate; the activity of 21-hydroxylase was reduced by approximately 20.0%. Japanese flounder is usually gonochoristic, with gonads that are either testes or ovaries. Here, we report an unusual case of hermaphroditism in Japanese flounder captured from the Bohai Sea. In the intersex flounder, the membrane of the upper ovary was closely connected to the abdominal muscles and internal organs, and the eggs filled the entire abdomen. The lower ovary was small and closely connected to the testes. The testes contained few fully mature sperm. Both eggs and sperm were capable of fertilization. The levels of several reproduction-related hormones (17β-estradiol, 11-ketotestosterone, 17α, 20β-dihydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone) in the intersex flounder were intermediate, between those in females and males. The results showed that the heterozygosity of the intersex flounder was 0.632, and there were 28 single-nucleotide polymorphisms in the cyp21a gene. Compared with that of wild flounder, the activity of 21-hydroxylase was reduced by approximately 20.0%, and expressions of cyp19a, amh, and dmrt1 differed. We present the first report of its kind, detailing the anatomy, hormonal endocrinology, molecular biology, and physiology of the intersex Japanese flounder. [ABSTRACT FROM AUTHOR]

Simple Summary: Expression quantitative trait locus (eQTL) analysis is crucial in revealing the genetic basis of complex traits, advancing the study of human diseases, optimizing the breeding of agricultural plants and animals, and gaining a deeper understanding of specific biological processes. The conventional analysis involves correlating genetic variants from whole-genome sequencing (WGS) data and gene expression, but to improve the power of eQTL detection, it is often necessary to expand the sample size as far as possible, ranging from hundreds to thousands. Large sample sizes for WGS are extremely costly, and this bottleneck is particularly evident in economically important agricultural animals. In contrast, the advantages of eQTL analyses from transcriptome data are obvious: cost-effective, simultaneous acquisition of variants and expression information. We propose to use transcriptome data alone for SNP calling and kmer generation, and then association analysis with gene expression. Here, 87 SNP-based and 35 kmer-based association results were obtained. Subsequently, comparison and validation of these two results revealed that they each have their own strengths and can complement each other, which promotes in-depth exploration of the regulatory relationship between genetic variants and gene expression. Traditional expression quantitative trait locus (eQTL) mapping associates single nucleotide polymorphisms (SNPs) with gene expression, where the SNPs are derived from large-scale whole-genome sequencing (WGS) data or transcriptome data. While WGS provides a high SNP density, it also incurs substantial sequencing costs. In contrast, RNA-seq data, which are more accessible and less expensive, can simultaneously yield gene expressions and SNPs. Thus, eQTL analysis based on RNA-seq offers significant potential applications. Two primary strategies were employed for eQTL in this study. The first involved analyzing expression levels in relation to variant sites detected between populations from RNA-seq data. The second approach utilized kmers, which are sequences of length k derived from RNA-seq reads, to represent variant sites and associated these kmer genotypes with gene expression. We discovered 87 significant association signals involving eGene on the basis of the SNP-based eQTL analysis. These genes include DYNLT1, NMNAT1, and MRLC2, which are closely related to neurological functions such as motor coordination and homeostasis, play a role in cellular energy metabolism, and function in regulating calcium-dependent signaling in muscle contraction, respectively. This study compared the results obtained from eQTL mapping using RNA-seq identified SNPs and gene expression with those derived from kmers. We found that the vast majority (23/30) of the association signals overlapping the two methods could be verified by haplotype block analysis. This comparison elucidates the strengths and limitations of each method, providing insights into their relative efficacy for eQTL identification. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is a commonly used immunosuppressive drug in solid organ transplantation. Pharmacogenetics has been demonstrated before to be decisive in TAC pharmacotherapy. The CYP3A5*3 variant has been reported to be the main determinant of TAC dose requirements; however, other polymorphisms have also proven to be influential, especially in CYP3A5 non-expressor patients. The aim of this study is to evaluate the influence of genetic polymorphisms in TAC therapy in a cohort of Spanish transplant recipients. Genetic analysis including ten polymorphic variants was performed, and demographic and clinical data and pharmacotherapy of 26 patients were analyzed. No significant differences were found in weight-adjusted dose between CYP3A5 expressors and non-expressors (0.047 mg/kg vs. 0.044 mg/kg), while they were found for carriers of the CYP3A4*1B allele (0.101 mg/kg; p < 0.05). The results showed that patients with at least one CYP3A4*1B allele had a higher TAC dose and lower blood concentration. Dose-adjusted TAC blood levels were also lower in CYP3A4*1B carriers compared to non-carriers (0.72 ng/mL/mg vs. 2.88 ng/mL/mg). These results support the independence of CYP3A5*3 and CYP3A4*1B variants as determinants of dose requirements despite the linkage disequilibrium present between the two. The variability in genotype frequency between ethnicities may be responsible for the discrepancy found between studies. [ABSTRACT FROM AUTHOR]

Tepary bean (Phaseolus acutifolius A. Gray) is a diploid legume species (2n = 2x = 22). It is the most drought- and heat-tolerant crop of the genus Phaseolus. Tepary bean is native to the northern part of Mexico and the south-western part of the U.S. The lack of molecular markers associated with agronomic traits such as 100-seed weight and seed yield limit the development of elite tepary bean cultivars. Therefore, the objectives of this study were to evaluate tepary bean for 100-seed weight and yield, and identify single-nucleotide polymorphism (SNP) markers associated with these traits. A total of 230,000 high-quality SNPs obtained from the whole-genome resequencing of 153 tepary bean accessions were used for this study. For 100-seed weight, a total of 5 and 20 SNPs were found using a mixed linear model (MLM) and compressed mixed linear model (cMLM), respectively. A candidate gene, Phacu.CVR.002G320800.13, encoding the squamosa promoter-binding protein-like (SBP domain) transcription factor family protein was found to be associated with 100-seed weight. For seed yield, a total of one and eight SNPs were identified using an MLM and cMLM, respectively. Phacu.CVR.009G294200.1, encoding for peroxidase family protein, was identified as a candidate gene for seed yield. Both Phacu.CVR.002G320800.13 and Phacu.CVR.009G294200.1 are likely to be involved in seed development of tepary bean. This is one of the few studies investigating the genetics of 100-seed weight and seed yield in tepary bean. [ABSTRACT FROM AUTHOR]

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes Astrotactin 1 (ASTN1), EBF Transcription Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-tRNA Specific (EEFSEC), Microtubule-Associated Serine/Threonine Kinase 1 (MAST1), and Tumor Necrosis Factor Alpha (TNF-α) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks' gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks' gestation), and 281 control women. The analysis of ASTN1 rs146756455, EBF1 rs2963463, EBF1 rs2946169, EEFSEC rs201450565, MAST1 rs188343966, and TNF-α rs1800629 SNPs was performed using TaqMan real-time PCR. p-values were Bonferroni-adjusted for multiple comparisons. EBF1 SNP rs2963463 was significantly associated with sPTB (p adj = 0.03). Women carrying the CC genotype had a 3–4-times lower risk of sPTB (p adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (p adj < 0.0001). All other associations were based on unadjusted p-values. The minor T allele of EBF1 SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (p = 0.045). Similarly, the CC genotype of ASTN1 SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (p = 0.019). Finally, the TNF-α SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (p < 0.05). The EBF1 SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, EBF1 SNP rs2946169 and ASTN1 SNP rs146756455, as well as TNF-α SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively. [ABSTRACT FROM AUTHOR]

Russian Snow White (RSW) chickens are characterized by high egg production, extreme resistance to low temperatures, disease resistance, and by the snow-white color of the day-old chicks. Studying the genome of this unique chicken breed will reveal its evolutionary history and help to understand the molecular genetic mechanisms underlying the unique characteristics of this breed, which will open new breeding opportunities and support future studies. We have sequenced and made a de novo assembly of the whole RSW genome using deep sequencing (250×) by the short reads. The genome consists of 40 chromosomes with a total length of 1.1 billion nucleotide pairs. Phylogenetic analysis placed the RSW near the White Leghorn, Fayoumi, and Houdan breeds. Comparison with other chicken breeds revealed a wide pool of mutations unique to the RSW. The functional annotation of these mutations showed the adaptation of genes associated with the development of the nervous system, thermoreceptors, purine receptors, and the TGF-beta pathway, probably caused by selection for low temperatures. We also found adaptation of the immune system genes, likely driven by selection for resistance to viral diseases. Integration with previous genome-wide association studies (GWAS) suggested several causal single nucleotide polymorphisms (SNPs). Specifically, we identified an RSW-specific missense mutation in the RALYL gene, presumably causing the snow-white color of the day-old chicks, and an RSW-specific missense mutation in the TLL1 gene, presumably affecting the egg weight. [ABSTRACT FROM AUTHOR]

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1–14 days, 15–30 days, 31–60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndrome (APS) comprises a complex association of autoimmune pathological conditions. APS Type 1 originates from loss-of-function mutations in the autoimmune regulator (AIRE) gene. APS2, APS3 and APS4 are linked to specific HLA alleles within the major histocompatibility complex, with single-nucleotide polymorphisms (SNPs) in non-HLA genes also contributing to disease. In general, variability in the AIRE locus and the presence of heterozygous loss-of-function mutations can impact self-antigen presentation in the thymus. In this study, whole-exome sequencing (WES) was performed on a sixteen-year-old female APS3A/B patient to investigate the genetic basis of her complex phenotype. The analysis identified two variants (p.Arg111Trp and p.Thr101Ile) of the hepatitis A virus cell receptor 2 gene (HAVCR2) encoding for the TIM-3 (T cell immunoglobulin and mucin domain 3) protein. These variants were predicted, through in silico analysis, to impact protein structure and stability, potentially influencing the patient's autoimmune phenotype. While confocal microscopy analysis revealed no alteration in TIM-3 fluorescence intensity between the PBMCs isolated from the patient and those of a healthy donor, RT-qPCR showed reduced TIM-3 expression in the patient's unfractionated PBMCs. A screening conducted on a cohort of thirty APS patients indicated that the p.Thr101Ile and p.Arg111Trp mutations were unique to the proband. This study opens the pathway for the search of TIM-3 variants possibly linked to complex autoimmune phenotypes, highlighting the potential of novel variant discovery in contributing to APS classification and diagnosis. [ABSTRACT FROM AUTHOR]

The Northern snakehead (Channa argus) is a significant economic aquaculture species in China. Exhibiting sexual dimorphism in the growth rate between females and males, mono-sex breeding holds substantial value for aquaculture. This study employed GWAS and transcriptome analysis were applied to identify sex determination genomic regions and develop sex-specific markers. A total of 270 single-nucleotide polymorphisms (SNPs) and 31 insertion-deletions (InDels) were identified as being sexually dimorphic through GWAS and fixation index (Fst) scanning. Based on GWAS results, two sex-specific InDel markers were developed, effectively distinguishing genetic sex for XX females, XY males, and YY super-males via (polymerase chain reaction) PCR amplification. A major genomic segment of approximately 115 kb on chromosome 3 (Chr 03) was identified as the sex-determination region. A comparative transcriptome analysis of gonads for three sexes identified 158 overlapping differentially expressed genes (DEGs). Additionally, three sex-related candidate genes were identified near the sex determination region, including id2, sox11, and rnf144a. Further studies are required to elucidate the functions of these genes. Overall, two sex-specific InDel markers support a male heterogametic XX/XY sex-determination system in Northern snakeheads and three candidate genes offer new insights into sex determination and the evolution of sex chromosomes in teleost fish. [ABSTRACT FROM AUTHOR]

Disease outbreaks in aquaculture have recently intensified. In particular, visceral white-nodules disease, caused by Pseudomonas plecoglossicida, has severely hindered the small yellow croaker (Larimichthys polyactis) aquaculture industry. However, research on this disease is limited. To address this gap, the present study employed a 100K SNP chip to genotype individuals from an F1 full-sib family, identify single nucleotide polymorphisms (SNPs), and construct a genetic linkage map for this species. A high-density genetic linkage map spanning a total length of 1395.72 cM with an average interval of 0.08 cM distributed across 24 linkage groups was obtained. Employing post-infection survival time as an indicator of disease resistance, 13 disease resistance-related quantitative trait loci (QTLs) were detected, and these regions included 169 genes. Functional enrichment analyses pinpointed 11 candidate disease resistance-related genes. RT-qPCR analysis revealed that the genes of chmp1a and arg1 are significantly differentially expressed in response to P. plecoglossicida infection in spleen and liver tissues, indicating their pivotal functions in disease resistance. In summary, in addition to successfully constructing a high-density genetic linkage map, this study reports the first QTL mapping for visceral white-nodules disease resistance. These results provide insight into the intricate molecular mechanisms underlying disease resistance in the small yellow croaker. [ABSTRACT FROM AUTHOR]

The obscure puffer (Takifugu obscurus) is a popular cultured species and accounts for around 50% of the total pufferfish production in China. A hybrid puffer was generated by crossing a female obscure puffer with a male tiger puffer (T. rubripes). Its growth model has not been developed and the genetic basis underlying its growth superiority has not yet been fully investigated. In this study, the growth model and morphological traits of the hybrid puffer were explored. The results indicated that the hybrid puffer exhibited a significant growth advantage compared to the obscure puffer. There were also significant differences in their morphological traits. We conducted genotyping-by-sequencing (GBS) on hybrid and obscure puffer groups, identifying 215,288 high-quality single nucleotide polymorphisms (SNPs) on 22 chromosomes. Subsequently, a total of 13 growth-related selection regions were identified via a combination of selection signatures and a genome-wide association study (GWAS); these regions were mainly located on chromosomes 10 and 22. Ultimately, the screened regions contained 13 growth-related genes, including itgav, ighv3-43, ighm, atp6v1b2, pld1, xmrk, inhba, dsp, dsg2, and dsc2, which regulate growth through a variety of pathways. Taken together, the growth models and candidate genes used in this study will aid our understanding of production characteristics and the genetic basis of growth rates. The hybrid will also be of great significance for the genome-assisted breeding of pufferfish in the future. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility. [ABSTRACT FROM AUTHOR]

Previous study revealed that isocitrate dehydrogenase (NADP (+)) 2, mitochondrial (IDH2), lactate dehydrogenase A (LDHA), and lactate dehydrogenase B (LDHB) genes were significantly differentially expressed in liver tissues of Holstein cows among different lactation periods and associated with lipid and protein metabolism; hence, they were considered as candidates for milk production traits. Herein, the genetic effects of the three genes on milk yield, fat, and protein traits were studied by association analysis using 926 Chinese Holstein cows from 45 sire families. As a result, five single nucleotide polymorphisms (SNPs) in IDH2, one in LDHA, and three in LDHB were identified by re-sequencing, and subsequently, they were genotyped in 926 Chinese Holstein cows by genotyping by target sequencing (GBTS). With the animal model, single-locus association analysis revealed that four SNPs in IDH2 and one SNP in LDHA were significantly associated with milk, fat, and protein yields (p ≤ 0.0491), and three SNPs in LDHB were associated with milk yield, milk fat yield, and fat percentage (p ≤ 0.0285). Further, four IDH2 SNPs were found to form a haplotype block significantly associated with milk yield, fat yield, protein yield, and protein percentage (p ≤ 0.0249). In addition, functional predictions indicated that one SNP in LDHA, g.26304153G>A, may affect transcription factor binding and two SNPs, g.88544541A>G and g.88556310T>C could alter LDHB mRNA secondary structure. In summary, this study profiled the significant genetic effects of IDH2, LDHA, and LDHB on milk yield and composition traits and provided referable genetic markers for genomic selection programs in dairy cattle. [ABSTRACT FROM AUTHOR]

The oculocutaneous albinism II (OCA2) gene encodes a melanosomal transmembrane protein involved in melanogenesis. Recent genome-wide association studies have identified several single nucleotide polymorphisms within OCA2 genes that are involved in skin pigmentation. Nevertheless, there have been no attempts to modulate this gene to improve skin discoloration. Accordingly, our aim was to identify compounds that can reduce OCA2 expression and to develop a formula that can improve skin brightness and reduce hyperpigmented spots. In this study, we investigated the effects of OCA2 expression reduction on melanin levels, melanosome pH, and autophagy induction through siRNA knockdown. Additionally, we identified several bioactives that effectively reduce OCA2 expression. Ultimately, in a clinical trial, we demonstrated that topical application of those compounds significantly improved skin tone and dark spots compared to vitamin C, a typical brightening agent. These findings demonstrate that OCA2 is a promising target for the development of efficacious cosmetics and therapeutics designed to treat hyperpigmentation. [ABSTRACT FROM AUTHOR]

Simple Summary: Heterozygosity is a fundamental measure used to compare the level of genetic variation between populations. However, such a comparison is influenced by the magnitude of selection pressure on the genomic regions used. Using the genomic regions free from selection, the heterozygosity of large populations was two times higher than that of small populations. However, this difference was only ~1.6 times for the heterozygosities estimated using the regions under selective constraints. This suggests an excess in the heterozygosities of constrained regions due to the presence of deleterious variants in small populations. This investigation found a correlation between the effective population size and the magnitude of the excess in the constrained-region diversity. Furthermore, the excess was found to be much higher for highly constrained genes and lower for genes under relaxed selective constraints. The excess was also higher for highly expressed genes compared to those with low expression levels. These results emphasize the use of neutral regions, less constrained genes, or lowly expressed genes when comparing the heterozygosities between populations. Heterozygosity is a fundamental measure routinely used to compare between populations to infer the level of genetic variation and their relative effective population sizes. However, such comparison is highly influenced by the magnitude of selection pressure on the genomic regions used. Using over 2 million Single Nucleotide Variants (SNVs) from chimpanzee and mouse populations, this study shows that the heterozygosities estimated using neutrally evolving sites of large populations were two times higher than those of small populations. However, this difference was only ~1.6 times for the heterozygosities estimated using nonsynonymous sites. This suggests an excess in the nonsynonymous heterozygosities due to the segregation of deleterious variants in small populations. This excess in the nonsynonymous heterozygosities of the small populations was estimated to be 23–31%. Further analysis revealed that the magnitude of the excess is modulated by effective population size (Ne) and selection intensity (s). Using chimpanzee populations, this investigation found that the excess in nonsynonymous diversity in the small population was little (6%) when the difference between the Ne values of large and small populations was small (2.4 times). Conversely, this was high (23%) when the difference in Ne was large (5.9 times). Analysis using mouse populations showed that the excess in the nonsynonymous diversity of highly constrained genes of the small population was much higher (38%) than that observed for the genes under relaxed selective constraints (21%). Similar results were observed when the expression levels of genes were used as a proxy for selection intensity. These results emphasize the use of neutral regions, less constrained genes, or lowly expressed genes when comparing the heterozygosities between populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Bipolar disorder is a psychiatric condition in which one prominent symptom is the regular occurrence of mood swings. Its root cause remains unclear; thus, this study was intended to provide new insights to better understand the genetics underlying such a disorder. Using samples obtained from three regions in the brain, it was found that some molecular and cellular mechanisms are involved in the disruption of neurobiological processes. The dysregulated expression of certain genes eventually leads to neurogenesis and neurotransmission impairment events in humans. Furthermore, these genes significant in the onset of bipolar disorder were identified and evaluated for the presence of variants, which may be targeted to engineer better curative treatment strategies for the disorder. Bipolar disorder (BPD) is a serious psychiatric condition that is characterized by the frequent shifting of mood patterns, ranging from manic to depressive episodes. Although there are already treatment strategies that aim at regulating the manifestations of this disorder, its etiology remains unclear and continues to be a question of interest within the scientific community. The development of RNA sequencing techniques has provided newer and better approaches to studying disorders at the transcriptomic level. Hence, using RNA-seq data, we employed intramodular connectivity analysis and network pharmacology assessment of disease-associated variants to elucidate the biological pathways underlying the complex nature of BPD. This study was intended to characterize the expression profiles obtained from three regions in the brain, which are the nucleus accumbens (nAcc), the anterior cingulate cortex (AnCg), and the dorsolateral prefrontal cortex (DLPFC), provide insights into the specific roles of these regions in the onset of the disorder, and present potential targets for drug design and development. The nAcc was found to be highly associated with genes responsible for the deregulated transcription of neurotransmitters, while the DLPFC was greatly correlated with genes involved in the impairment of components crucial in neurotransmission. The AnCg did show association with some of the expressions, but the relationship was not as strong as the other two regions. Furthermore, disease-associated variants or single nucleotide polymorphisms (SNPs) were identified among the significant genes in BPD, which suggests the genetic interrelatedness of such a disorder and other mental illnesses. DRD2, GFRA2, and DCBLD1 were the genes with disease-associated variants expressed in the nAcc; ST8SIA2 and ADAMTS16 were the genes with disease-associated variants expressed in the AnCg; and FOXO3, ITGA9, CUBN, PLCB4, and RORB were the genes with disease-associated variants expressed in the DLPFC. Aside from unraveling the molecular and cellular mechanisms behind the expression of BPD, this investigation was envisioned to propose a new research pipeline in studying the transcriptome of psychiatric disorders to support and improve existing studies. [ABSTRACT FROM AUTHOR]

Four types of archaeogenetic data mining are used to investigate the origin of the Minoans and the Uralic peoples: (1) six SNP mutations related to eye, hair, and skin phenotypes; (2) whole-genome admixture analysis using the G25 system; (3) an analysis of the history of the U5 mitochondrial DNA haplogroup; and (4) an analysis of the origin of each currently known Minoan mitochondrial and y-DNA haplotypes. The uniform result of these analyses is that the Minoans and the Uralic peoples had a common homeland in the lower and middle Danube Basin, as well as the Black Sea coastal regions. This new result helps to reconcile archaeogenetics with linguistics, which have shown that the Minoan language belongs to the Uralic language family. [ABSTRACT FROM AUTHOR]

Red clover (Trifolium pratense L.) is a well-appreciated grassland crop in temperate climates but suffers from increasingly frequent and severe drought periods. Molecular markers for drought resilience (DR) would benefit breeding initiatives for red clover, as would a better understanding of the genes involved in DR. Two previous studies, as follows, have: (1) identified phenotypic DR traits in a diverse set of red clover accessions; and (2) produced genotypic data using a pooled genotyping-by-sequencing (GBS) approach in the same collection. In the present study, we performed genome-wide association studies (GWAS) for DR using the available phenotypic and genotypic data. Single nucleotide polymorphism (SNP) calling was performed using GBS data and the following two red clover genome assemblies: the recent HEN-17 assembly and the Milvus assembly. SNP positions with significant associations were used to delineate flanking regions in both genome assemblies, while functional annotations were retrieved from Medicago truncatula orthologs. GWAS revealed 19 significant SNPs in the HEN-17-derived SNP set, explaining between 5.3 and 23.2% of the phenotypic variation per SNP–trait combination for DR traits. Among the genes in the SNP-flanking regions, we identified candidate genes related to cell wall structuring, genes encoding sugar-modifying proteins, an ureide permease gene, and other genes linked to stress metabolism pathways. GWAS revealed 29 SNPs in the Milvus-derived SNP set that explained substantially more phenotypic variation for DR traits, between 5.3 and 42.3% per SNP–trait combination. Candidate genes included a DEAD-box ATP-dependent RNA helicase gene, a P-loop nucleoside triphosphate hydrolase gene, a Myb/SANT-like DNA-binding domain protein, and an ubiquitin–protein ligase gene. Most accessions in this study are genetically more closely related to the Milvus genotype than to HEN-17, possibly explaining how the Milvus-derived SNP set yielded more robust associations. The Milvus-derived SNP set pinpointed 10 genomic regions that explained more than 25% of the phenotypic variation for DR traits. A possible next step could be the implementation of these SNP markers in practical breeding programs, which would help to improve DR in red clover. Candidate genes could be further characterized in future research to unravel drought stress resilience in red clover in more detail. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the genetics behind the reproductive traits of pigs is crucial for enhancing productivity and economic outcomes in the pork industry. In this study, we investigated the genetic factors influencing reproductive characteristics in Large White pigs. By analyzing the genetic data of 2237 sows from southern China, we identified specific genes and genetic markers associated with important reproductive traits, such as litter size. Our findings provide valuable insights that could help in developing targeted breeding strategies aimed at improving these traits. This research is not only significant for farmers and breeders but also contributes to a more sustainable and efficient approach to pig farming. (1) Background: Reproductive performance is crucial for the pork industry's success. The Large White pig is central to this, yet the genetic factors influencing its reproductive traits are not well understood, highlighting the need for further research. (2) Methods: This study utilized Genome-Wide Association Studies to explore the genetic basis of reproductive traits in the Large White pig. We collected data from 2237 Large White sows across four breeding herds in southern China, focusing on eight reproductive traits. Statistical analyses included principal component analysis, linkage disequilibrium analysis, and univariate linear mixed models to identify significant single-nucleotide polymorphisms and candidate genes. (3) Results: Forty-five significantly related SNPs and 17 potential candidate genes associated with litter traits were identified. Individuals with the TT genotype at SNP rs341909772 showed an increase of 1.24 in the number of piglets born alive (NBA) and 1.25 in the number of healthy births (NHBs) compared with those with the CC genotype. (4) Conclusions: The SNPs and genes identified in this study offer insights into the genetics of reproductive traits in the Large White pig, potentially guiding the development of breeding strategies to improve litter size. [ABSTRACT FROM AUTHOR]

Simple Summary: The curliness of the white wool in Chinese Tan sheep gradually diminishes as the sheep age, but our knowledge of what underpins this change is still limited. To further our understanding, this study characterised the ovine KRTAP19-3 gene, and the results suggest that variation in the gene affects fibre diameter variability for the heterotypic hair fibres of these sheep. Wool, a natural fibre derived from sheep, can present a challenge to wool processing and manufacturing industries because of the variation in fibre traits. Genetic improvement offers one solution to this challenge, and having a better understanding of the genes that affect wool fibre traits is therefore important. Here, we describe ovine KRTAP19-3, a new member of the KAP19 gene family. Phylogenetic analysis revealed its relationship to other known KRTAP19 gene sequences, and an analysis of the nucleotide sequence variation in KRTAP19-3 from 288 sheep of a variety of breeds revealed six unique variant sequences. Among these variants, eleven single nucleotide polymorphisms (SNPs) were detected, with six located in the coding region. Three of these coding region SNPs were non-synonymous and would result in amino acid changes. Associations were observed between the presence of specific sequence variants in Chinese Tan sheep and wool trait variation, particularly an increase in fibre diameter variability in the heterotypic hair fibres. These findings enhance our understanding of the genes that encode sheep wool proteins. [ABSTRACT FROM AUTHOR]

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms. [ABSTRACT FROM AUTHOR]

The oil content of maize kernels is essential to determine its nutritional and economic value. A multiparent population (MPP) consisting of five recombinant inbred line (RIL) subpopulations was developed to elucidate the genetic basis of the total oil content (TOC) in maize. The MPP used the subtropical maize inbred lines CML312 and CML384, along with the tropical maize inbred lines CML395, YML46, and YML32 as the female parents, and Ye107 as the male parent. A genome-wide association study (GWAS) was performed using 429 RILs of the multiparent population across three environments, employing 584,847 high-quality single nucleotide polymorphisms (SNPs). Furthermore, linkage analysis was performed in the five subpopulations to identify quantitative trait loci (QTL) linked to TOC in maize. Through QTL mapping and GWAS, 18 QTLs and 60 SNPs that were significantly associated with TOC were identified. Two novel candidate genes, Zm00001d029550 and Zm00001d029551, related to TOC in maize and located on chromosome 1 were reported, which have not been previously reported. These genes are involved in biosynthesis, lipid signal transduction, plant development and metabolism, and stress responses, potentially influencing maize TOC. Haplotype analysis of Zm00001d029550 and Zm00001d029551 revealed that Hap3 could be considered a superior haplotype for increasing TOC in maize. A co-located SNP (SNP-75791466) on chromosome 1, located 5648 bp and 11,951 bp downstream of the candidate genes Zm00001d029550 and Zm00001d029551, respectively, was found to be expressed in various maize tissues. The highest expression was observed in embryos after pollination, indicating that embryos are the main tissue for oil accumulation in maize. This study provides a theoretical basis for understanding the genetic mechanisms underlying maize TOC and developing high-quality, high-oil maize varieties. [ABSTRACT FROM AUTHOR]

Disorders of sexual development (DSDs) in dogs, similar to humans, arise from genetic mutations, gonadal differentiation, or phenotypic sex development. The French Bulldog, a breed that has seen a surge in popularity and demand, has also shown a marked increase in DSD incidence. This study aims to characterize the genetic underpinnings of DSDs in a French Bulldog named Brutus, exhibiting ambiguous genitalia and internal sexual anatomy, and to explore the impact of breeding practices on genetic diversity within the breed. We utilized a comprehensive approach combining conventional cytogenetics, molecular techniques, and deep sequencing to investigate the genetic profile of Brutus. The sequence data were compared to three other male French Bulldogs' genome sequences with typical reproductive anatomy, including Brutus's father and the canine reference genome (CanFam6). We found a Robertsonian fusion involving chromosome 23 previously reported in dogs as a causative mutation responsible for sex reversal syndrome. Our findings revealed a 22% mosaicism (78,XX/77,XX), the absence of the sex-determining region (SRY) gene, and the presence of 43 unique Single Nucleotide Variants (SNVs) not inherited from the father. Notably, the run of homozygosity (ROH) analysis showed Brutus has a higher number of homozygous segments compared to other Bulldogs, with a total length of these fragments 50% greater than the average, strongly suggesting this dog is the product of the mating between siblings. Although no direct causative genes for the DSD phenotype were identified, four candidate loci warrant further investigation. Our study highlighted the need for a better annotated and curated reference dog genome to define genes causative of any specific phenotype, suggests a potential genetic basis for the DSD phenotype in dogs, and underscores the consequences of uncontrolled breeding practices in French Bulldogs. These findings highlight the importance of implementing strategic genetic management to preserve genetic health and diversity in canine populations. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is one of the most common types. There is strong evidence that ryanodine receptor 2 (RYR2) plays an important role in different types of cancer according to previous studies. Its expression is associated with survival in patients with HNSCC, but it is unknown whether altered RYR2 expression contributes to tumorigenesis. Therefore, we examined how RYR2 polymorphisms affect OSCC susceptibility and clinicopathological characteristics. Five single nucleotide polymorphisms (SNPs) of RYR2, rs12594, rs16835904, rs2779359, rs3765097, and rs3820216, were analyzed in 562 cases of OSCC and 332 healthy controls using real-time PCR. We demonstrated that RYR2 SNP rs12594 was significantly different between the case and control groups, but this difference was not significant after adjusting for personal habits. In contrast, we found that different genotypes of SNP rs2779359 were significantly associated with the characteristics of clinical stage and tumor size in OSCC patients, according to the odds ratios and the adjusted odds ratios; specifically, patients with the T genotype had 1.477-fold (95% CI, 1.043 to 2.091; p = 0.028) and 1.533-fold (95% CI, 1.087–2.162; p = 0.015) increases in clinical stage and tumor size, respectively, compared with patients with the C allele. The results of our study, in which RYR2 SNPs associated with OSCC progression and development were examined for the first time, suggest that clinicopathological characteristics may alter OSCC susceptibility. Finally, RYR2 SNP rs2779359 not only plays a role in both the prognosis and diagnosis of oral cancer but is also likely an important predictive factor for recurrence, response to treatment, and medication toxicity. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84–4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06–2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women. [ABSTRACT FROM AUTHOR]

Understanding the genetic basis of species differences in flowering time and inflorescence architecture can shed light on speciation and molecular breeding. Melastoma shows rapid speciation, with about 100 species formed in the past few million years, and, meanwhile, possesses high ornamental values. Two largely sympatric and closely related species of this genus, M. candidum and M. normale, differ markedly in flowering time and flower number per inflorescence. Here, we constructed an F2 population between M. candidum and M. normale, and used extreme bulks for flowering time and flower number per inflorescence in this population to identify genomic regions underlying the two traits. We found high differentiation on nearly the whole chromosome 7 plus a few regions on other chromosomes between the two extreme bulks for flowering time. Large chromosomal inversions on chromosome 7 between the two species, which contain flowering-related genes, can explain recombinational suppression on the chromosome. We identified 1872 genes with one or more highly differentiated SNPs between the two bulks for flowering time, including CSTF77, FY, SPA3, CDF3, AGL8, AGL15, FHY1, COL9, CIB1, FKF1 and FAR1, known to be related to flowering. We also identified 680 genes with one or more highly differentiated SNPs between the two bulks for flower number per inflorescence, including PNF, FIL and LAS, knows to play important roles in inflorescence development. These large inversions on chromosome 7 prevent us from narrowing down the genomic region(s) associated with flowering time differences between the two species. Flower number per inflorescence in Melastoma appears to be controlled by multiple genes, without any gene of major effect. Our study indicates that large chromosomal inversions can hamper the identification of the genetic basis of important traits, and the inflorescence architecture of Melastoma species may have a complex genetic basis. [ABSTRACT FROM AUTHOR]

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case–control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (<10 years or ≥10 years). Genotypes were determined by real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17–6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to understand why some people with lung adenocarcinoma, a type of lung cancer, survive longer than others, even when their conditions seem similar. By studying the DNA of 1464 patients, we found six specific genetic differences that appear to affect survival. These differences are located in parts of the DNA that do not directly make proteins but might control how certain genes are turned on or off. The goal is to use this information to predict which patients might have better outcomes and to develop more personalized treatment options. Further research is needed to confirm these results and to understand the underlying biological mechanisms, but our findings could eventually improve how we treat lung cancer and understand its outcomes better. Background/Objectives: Lung cancer remains a global health concern, with substantial variation in patient survival. Despite advances in detection and treatment, the genetic basis for the divergent outcomes is not understood. We investigated germline polymorphisms that modulate overall survival in 1464 surgically resected lung adenocarcinoma patients. Methods: A multivariable Cox proportional hazard model was used to assess the association of more than seven million polymorphisms with overall survival at the 60-month follow-up, considering age, sex, pathological stage, decade of surgery and principal components as covariates. Genes in which variants were identified were studied in silico to investigate functional roles. Results: Six germline variants passed the genome-wide significance threshold. These single nucleotide polymorphisms were mapped to non-coding (intronic) regions on chromosomes 2, 3, and 5. The minor alleles of rs13000315, rs151212827, and rs190923216 (chr. 2, 3 and 5, respectively) were found to be independent negative prognostic factors. All six variants have been reported to regulate the expression of nine genes, seven of which are protein-coding, in different tissues. Survival-associated variants on chromosomes 2 and 3 were already reported to regulate the expression of NT5DC2 and NAGK, with high expression associated with the minor alleles. High NT5DC2 and NAGK expression in lung adenocarcinoma tissue was already shown to correlate with poor overall survival. Conclusions: This study highlights a potential regulatory role of the identified polymorphisms in influencing outcome and suggests a mechanistic link between these variants, gene expression regulation, and lung adenocarcinoma prognosis. Validation and functional studies are warranted to elucidate the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

The quality of corn kernels is crucial for their nutritional value, making the enhancement of kernel quality a primary objective of contemporary corn breeding efforts. This study utilized 260 corn inbred lines as research materials and assessed three traits associated with grain quality. A genome-wide association study (GWAS) was conducted using the best linear unbiased estimator (BLUE) for quality traits, resulting in the identification of 23 significant single nucleotide polymorphisms (SNPs). Additionally, nine genes associated with grain quality traits were identified through gene function annotation and prediction. Furthermore, a total of 697 quantitative trait loci (QTL) related to quality traits were compiled from 27 documents, followed by a meta-QTL analysis that revealed 40 meta-QTL associated with these traits. Among these, 19 functional genes and reported candidate genes related to quality traits were detected. Three significant SNPs identified by GWAS were located within the intervals of these QTL, while the remaining eight significant SNPs were situated within 2 Mb of the QTL. In summary, the findings of this study provide a theoretical framework for analyzing the genetic basis of corn grain quality-related traits and for enhancing corn quality. [ABSTRACT FROM AUTHOR]

Watermelon (Citrullus spp.) is an economically important crop globally, but it is susceptible to various diseases, including powdery mildew. Previous studies have identified genetic factors associated with powdery mildew resistance. However, further research using diverse genetic approaches is necessary to elucidate the underlying genetic mechanisms of this resistance. In this study, the germplasm collection comprising highly homozygous inbred lines was employed, which enabled the accumulation of consistent data and improved the reliability of the genome-wide association study (GWAS) findings. Our investigation identified two significant single-nucleotide polymorphisms (SNPs), pm2.1 and pm3.1, which were strongly associated with disease resistance. Moreover, several candidate genes were revealed within the linkage disequilibrium (LD) blocks surrounding the significant SNPs. In conclusion, the identification of significant SNPs and their additive effects, combined with the discovery of relevant candidate genes, expanded our understanding of the genetic basis of disease resistance and can pave the way for the development of more resilient watermelon cultivars through marker-assisted selection. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene—specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774—and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD. [ABSTRACT FROM AUTHOR]

Background/Objectives: 8-hydroxy-2′-deoxyguanosine (8-OHdG) is a form of oxidative DNA damage caused by oxidative stress (OS), which is considered a major factor in male infertility. The cellular defense system against 8-OHdG involves base excision repair (BER) with the enzyme 8-Oxoguanine DNA glycosylase 1 (OGG1). However, studies on the single-nucleotide polymorphism (SNP) OGG1 Ser326Cys have demonstrated that the Cys326Cys genotype could be the cause of an increment in oxidative DNA damage. In this study, the OGG1 Ser326Cys polymorphism and its effect on DNA oxidation were evaluated in 118 infertile men. Methods: Polymorphic screening was performed using TaqMan allelic discrimination assays, and oxidative DNA damage was evaluated through the quantification of 8-OHdG and total antioxidant capacity (TAC); in addition, electrical bioimpedance spectroscopy (EBiS) measurements were used as a reference for different electrical properties associated with 8-OHdG concentrations. Results: The detected Cys (G) allele frequency (0.4) was higher compared to the allele frequency reported in the "Allele Frequency Aggregator" (ALFA) and "Haplotype Map" (HapMap) projects for American populations (0.21–0.29), suggesting that the Cys (G) allele carrier could be a factor associated with American infertile populations. The values of 8-OHdG were twofold higher in carriers of the Cys326Cys (GG) genotype than the other genotypes and, in concordance, the TAC levels were threefold lower in Cys326Cys (GG) genotype carriers compared to the other genotypes. Moreover, the EBiS magnitude exhibited potential for the detection of different oxidative damage in DNA samples between genotypes. Conclusions: The Cys326Cys (GG) genotype is associated with oxidative DNA damage that could contribute to male infertility. [ABSTRACT FROM AUTHOR]

Background: Gliomas are neoplasms of the central nervous system that originate in glial cells. The genetic characteristics of this type of neoplasm are the loss of function of tumor suppressor genes such as TP53 and somatic mutations in genes such as IDH1/2. Additionally, in clinical cases, de novo single nucleotide polymorphisms (SNP) are reported, of which their pathogenicity and their effects on the function and stability of the protein are known. Methodology: Non-synonymous SNPs were analyzed for their structural and functional effect on proteins using a set of bioinformatics tools such as SIFT, PolyPhen-2, PhD-SNP, I-Mutant 3.0, MUpro, and mutation3D. A structural comparison between normal and mutated residues for disease-associated coding SNPs was performed using TM-aling and the SWISS MODEL. Results: A total of 13 SNPs were obtained for the TP53 gene, 1 SNP for IDH1, and 1 for IDH2, which would be functionally detrimental and associated with disease. Additionally, these changes compromise the structure and function of the protein; the A161S SNP for TP53 that has not been reported in any databases was classified as detrimental. Conclusions: All non-synonymous SNPs reported for TP53 were in the region of the deoxyribonucleic acid (DNA) binding domain and had a great impact on the function and stability of the protein. In addition, the two polymorphisms detected in IDH1 and IDH2 genes compromise the structure and activity of the protein. Both genes are related to the development of high-grade gliomas. All the data obtained in this study must be validated through experimental approaches. [ABSTRACT FROM AUTHOR]

Background/Objectives: We aimed to investigate the genetic loci related to disc hemorrhage (DH) and the relationship of causation between DH and primary open-angle glaucoma (POAG) using a genome-wide association study (GWAS) in East Asian individuals. Methods: The GWAS included 8488 Koreans who underwent ocular examination including fundus photography to determine the presence of DH and POAG. We performed a GWAS to identify significant single-nucleotide polymorphisms (SNPs) associated with DH and analyzed the heritability of DH and genetic correlation between DH and POAG. The identified SNPs were utilized as instrumental variables (IVs) for two-sample Mendelian randomization (MR) analysis. The POAG outcome dataset was adopted from Biobank Japan data (n = 179,351). Results: We found that the rs62463744 (TMEM270;ELN), rs11658281 (CCDC42), and rs77127203 (PDE10A;LINC00473) SNPs were associated with DH. The SNP heritability of DH was estimated to be 6.7%, with an absence of a genetic correlation with POAG. MR analysis did not reveal a causal association between DH and POAG for East Asian individuals. Conclusions: The novel loci underlying DH in the Korean cohort revealed SNPs in the ELN, CCDC41, and LINC00473 genes. The absence of a causal association between DH and POAG implies that DH is a shared risk factor, rather than an independent culprit factor, and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Caregiver–infant reciprocity is related to infant/toddler development and health. However, there is a dearth of research on reciprocity variables like co-occupation and developmental variables such as infant/toddler sensory processing/preferences, and it is important to understand the biopsychosocial mediators of these relations. These include novel genetic markers like maternal oxytocin receptor single-nucleotide polymorphisms (OXTR SNPs). Therefore, this study examined whether mothers carrying risk alleles for three OXTR SNPs displayed different co-occupational behaviors with their infants and whether their infants/toddlers showed different sensory processing/preferences. Methods: Data from the Infant Development and Healthy Outcomes in Mothers Study included prenatal saliva samples assayed for OXTR SNPs, 6-month postnatal behavioral observations coded for maternal–infant co-occupations (reciprocal emotionality, physicality, and intentionality), and 10-, 14-, and 18-month postnatal, maternal-reported Infant/Toddler Sensory Profiles (classified as within or outside the majority range for low registration, sensory seeking, sensory sensitivity, and sensory avoiding). Results: Mothers with rs53576 risk allele A engaged in more frequent reciprocal emotionality, while those with rs2254298 risk allele A engaged in less frequent reciprocal emotionality but more frequent reciprocal intentionality. Mothers with rs53576 risk allele A had infants with 11 times greater odds of being outside of the majority range for sensation avoiding at 10 months old. Conclusions: The results converge with the literature supporting links between OXTR SNPs, caregiver reciprocity, and infant/toddler development but extend the findings to relatively novel constructs (caregiver–infant co-occupations and infant/toddler sensory processing/preferences). [ABSTRACT FROM AUTHOR]

Host genetic variation has been recognized as a key predictor of diverse clinical sequelae among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. Insights into the link between the Interleukin-6 receptor (IL-6R) and Interleukin-1 beta (IL-1β) genetic variation and severe coronavirus disease 2019 (COVID-19) are crucial for developing new predictors and therapeutic targets. We aimed to investigate the association of IL-6R rs12083537, IL-1β rs16944, and IL-1β rs1143634 SNPs with the severity of COVID-19. Our study was conducted on 300 COVID-19-negative individuals (control group) and 299 COVID-19-positive cases, classified into mild, moderate, and severe subgroups. Analyses of IL-1β (rs16944, rs1143634) and IL-6R (rs12083537) SNPs' genotypes were performed using qPCR genotyping assays. The IL-1β (rs16944) CC genotype and IL-6R (rs12083537) GG genotype were substantially related to COVID-19 severity, which was also associated with comorbidities and some laboratory parameters (p < 0.001). The IL-1β (rs1143634) TT genotype was found to be protective. Likewise, the IL-1β (rs16944) CC genotype was associated with increased mortality. IL-1β rs16944 and IL-6R rs12083537 SNPs are promising potential predictors of SARS-CoV-2 disease severity. Meanwhile, the rs1143634 SNP T allele was protective against severity and mortality risk. [ABSTRACT FROM AUTHOR]