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Background: Emerging evidence has indicated possible efficacy benefit of platinum‐based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple‐negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results. Materials and Methods: Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum‐based neoadjuvant treatment. We prospectively enrolled women with stage IIB‐IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline‐based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease‐free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled. Results: The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3‐year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS. Conclusions: Platinum‐based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline‐ and taxane‐based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers. [ABSTRACT FROM AUTHOR]

Background: The shea tree is a well-known carbon sink in Africa that requires a sustainable conservation of its gene pool. However, the genetic structure of its population is not well studied, especially in Côte d’Ivoire. In this study, 333 superior shea tree genotypes conserved in situ in Côte d’Ivoire were collected and genotyped with the aim of investigating its genetic diversity and population structure to facilitate suitable conservation and support future breeding efforts to adapt to climate change effects. Results: A total of 7,559 filtered high-quality single nucleotide polymorphisms (SNPs) were identified using the genotyping by sequencing technology. The gene diversity (HE) ranged between 0.1 to 0.5 with an average of 0.26, while the polymorphism information content (PIC) value ranged between 0.1 to 0.5 with an average of 0.24, indicating a moderate genetic diversity among the studied genotypes. The population structure model classified the 333 genotypes into three genetic groups (GP1, GP2, and GP3). GP1 contained shea trees that mainly originated from the Poro, Tchologo, and Hambol districts, while GP2 and GP3 contained shea trees collected from the Bagoué district. Analysis of molecular variance (AMOVA) identified 55% variance within populations and 45% variance within individuals, indicating a very low genetic differentiation (or very high gene exchange) between these three groups (FST = 0.004, gene flow Nm = 59.02). Morphologically, GP1 displayed spreading tree growth habit, oval nut shape, higher mean nut weight (10.62 g), wide leaf (limb width = 4.63 cm), and small trunk size (trunk circumference = 133.4 cm). Meanwhile, GP2 and GP3 showed similar morphological characteristics: erect and spreading tree growth habit, ovoid nut shape, lower mean nut weight (GP2: 8.89 g; GP3: 8.36 g), thin leaf (limb width = 4.45 cm), and large trunk size (GP2: 160.5 cm, GP3: 149.1 cm). A core set of 100 superior shea trees, representing 30% of the original population size and including individuals from all four study districts, was proposed using the “maximum length sub-tree function” in DARwin v. 6.0.21. Conclusion: These findings provide new knowledge of the genetic diversity and population structure of Ivorian shea tree genetic resources for the design of effective collection and conservation strategies for the efficient use of inbreeding. [ABSTRACT FROM AUTHOR]

Cancer ranks as the second leading cause of mortality worldwide, prompting extensive investigations into factors contributing to its development. Among these factors, genetic variations, known as genotypic polymorphisms, have been identified as significant influencers in the susceptibility to various types of cancer. Recent research has focused on exploring the connection between polymorphisms in the Long Non-coding RNA HOTAIR and cancer risk. However, the results from these studies have been inconsistent, leading to ambiguity and controversy. To address this uncertainty, we conducted a systematic analysis by gathering relevant studies from PubMed, EMBASE, and Google Scholar. Specifically, we focused on three well-studied polymorphisms within the HOTAIR lncRNA (HOTAIR rs920778 C > T, HOTAIR rs1899663 G > T, HOTAIR rs4759314 A > G) and their association with cancer risk. Our meta-analysis included data from 48 case–control studies involving 42,321 cases and 54,137 controls. The results of our updated meta-analysis revealed a significant correlation between HOTAIR rs1899663 G > T and HOTAIR rs4759314 A > G polymorphisms and overall cancer risk, particularly in the homozygous and recessive genetic models. Subgroup analysis further revealed that these associations were notably pronounced in the Asian population but not observed in the Iranian population. Furthermore, our findings underscore the potential of HOTAIR polymorphisms as diagnostic markers for overall cancer risk, particularly in gynecological cancers, precisely, HOTAIR rs1899663 G > T polymorphism in breast cancer. In conclusion, our systematic analysis provides compelling evidence that Long Non-coding RNA HOTAIR polymorphisms are linked to cancer risk, particularly in certain populations and cancer types, suggesting their potential clinical relevance as diagnostic indicators. [ABSTRACT FROM AUTHOR]

Introduction: Male pattern baldness (MPB), also known as androgenetic alopecia, represents the most prevalent form of progressive hair loss in humans. It is characterized by a distinctive pattern of hair loss progression from the scalp; however, its underlying mechanism remains elusive and is influenced by hereditary, immune, and environmental factors. Genome-wide association studies (GWASs) have uncovered numerous risk genes/loci among European individuals with MPB. However, the validation of these susceptibility genes/loci within Han Chinese men remains largely unexplored. The aim of this study was to investigate whether the 71 susceptibility loci identified in a recent GWAS among European men also confer risk for MPB in Chinese men. Methods: Forty-seven single nucleotide polymorphisms (SNPs) previously reported in GWASs of MPB were selected and genotyped in independent individuals comprising 499 Han Chinese cases and 1,489 controls using the Sequenom MassArray system. After stringent quality control measures, 25 SNPs were subjected to statistical analyses. Cochran-Armitage trend test was used to evaluate the association between SNPs and disease susceptibility. To address multiple tests, Bonferroni correction was conducted, setting the threshold for statistical significance at a p-value <2 × 10-3 (0.05/25). Results: The rs13405699 SNP located at 2q31.1 exhibited a significant association with MPB in Han Chinese men (p = 4.84 × 10-5, OR = 1.37, 95% CI: 1.18-1.59). Moreover, the difference in rs13405699 genotype distribution between MPB cases and controls was statistically significant (p = 7.00 × 10-5). Genotype-based association analysis suggested that the recessive model provided the best fit for the rs13405699 polymorphism. Conclusion: This study represents the first confirmation of the association between the rs13405699 SNP at 2q31.1 and MPB within the Han Chinese population, thereby enhancing our understanding of the genetic underpinnings of MPB. [ABSTRACT FROM AUTHOR]

There is rising recognition of the importance of vitamin D (VD) in human reproduction. The vitamin D receptor (VDR) in the human genome is encoded by the VDR gene found on chromosome 12cenq12 which comprises 14 exons. The VDR gene polymorphisms such as ApaI, BsmI, FokI, and TaqI take part in susceptibility and progression of Polycystic Ovary Syndrome (PCOS). The VDR gene's non-coding regions have the BsmI (rs1544410) and ApaI (rs7975232) polymorphisms. The 3′ coding regions contain the FokI polymorphism (rs2228570) and TaqI (rs731236) polymorphisms, which influence functional activity by producing a lengthier VDR protein with lower transcriptional activity. These variants are related to fertility and reproductive health in females, metabolic disturbances like insulin resistance, obesity, and diabetes. The FokI polymorphism, located in exon 2 of the VDR gene, involves a nucleotide substitution from A to G, impacting mRNA stability, translational activity, and ultimately VDR levels and VD function, associated with the risk of PCOS in females. In PCOS, research indicates associations between these polymorphisms and metabolic, hormonal, and fertility factors. For instance, the BsmI polymorphism correlates with PCOS risk, while TaqI polymorphism may influence metabolic variables and hormone levels. These findings underscore the role of VDR gene polymorphisms in PCOS pathogenesis and highlight their potential as genetic markers for assessing PCOS risk and metabolic profiles. [ABSTRACT FROM AUTHOR]

The disease caused by Largemouth bass ranavirus (LMBV) is one of the most severe viral diseases in largemouth bass (Micropterus salmoides). It is crucial to evaluate the genetic resistance of largemouth bass to LMBV and develop markers for disease-resistance breeding. In this study, 100 individuals (45 resistant and 55 susceptible) were sequenced and evaluated for resistance to LMBV and a total of 2,579,770 variant sites (SNPs-single-nucleotide polymorphisms (SNPs) and insertions–deletions (InDels)) were identified. A total of 2348 SNPs-InDels and 1018 putative candidate genes associated with LMBV resistance were identified by genome-wide association analyses (GWAS). Furthermore, GO and KEGG analyses revealed that the 10 candidate genes (MHC II, p38 MAPK, AMPK, SGK1, FOXO3, FOXO6, S1PR1, IL7R, RBL2, and GADD45) were related to intestinal immune network for IgA production pathway and FoxO signaling pathway. The acquisition of candidate genes related to resistance will help to explore the molecular mechanism of resistance to LMBV in largemouth bass. The potential polymorphic markers identified in this study are important molecular markers for disease resistance breeding in largemouth bass. [ABSTRACT FROM AUTHOR]

Background: An escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD. Methods: Summary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings. Results: We identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD. Limitations: The GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders. Conclusion: Based on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders. [ABSTRACT FROM AUTHOR]

Litter size is an important reproductive trait of goats and is essential for their commercial production. Currently, there is a lack of feeding and breeding management and a disregard for fertility traits, such as litter size, during hybrid production. Therefore, in this study, we conducted whole-genome resequencing of the high- and low-fecundity hybrid white goats to determine the genes associated with fertility. In this study, we selected 6 ewes from more than 150 breeding populations and divided them into high- and low-fecundity groups (H group and L group, respectively; n = 3/group) and collected their blood and ovarian tissue samples for WGR analysis. The results of WGR analysis revealed the presence of several genetic variations, including single nucleotide polymorphisms, insertions or deletions, structural variations, and copy number variations, between the genomes of the two groups. Annotation and KEGG pathway analysis of the mutation data revealed that most of the genes were enriched in 19 biological pathways. Among these, we selected a few pathways associated with fertility and identified the genes that were specific to the H group. The results revealed that the SNPs in the genes LHCGR, JAK3, GDF9, GnRHR, and CIZ1 and the InDels in the genes PCDHAC1, RXRG, AGO2, CNOT10, TEAD4, and TAF10 were specific to the H group, suggesting that these genes may be associated with their high lambing performance. The results of our study provide insights into the optimization of management strategies for goats with different reproductive performances. [ABSTRACT FROM AUTHOR]

Background: The minor G-allele of FOXO3 rs2802292 is associated with human longevity. The aim of this study was to test the protective effect of the variant against the association with type 2 Diabetes and NAFLD. Methods: rs2802292 was genotyped in a large population of middle-aged subjects (n = 650) from a small city in Southern Italy. All participants were interviewed to collect information about lifestyle and dietary habits; clinical characteristics were recorded, and blood samples were collected from all subjects. The association between rs2802292 and NAFLD or diabetes was tested using a logistic model and mediation analysis adjusted for covariates. Results: Overall, the results indicated a statistical association between diabetes and rs2802292, especially for the TT genotype (OR = 2.14, 1.01 to 4.53 95% C.I., p = 0.05) or in any case for those who possess the G-allele (OR = 0.45, 0.25 to 0.81 95% C.I., p = 0.008). Furthermore, we found a mediation effect of rs2802292 on diabetes (as mediator) and NAFLD. There is no direct relationship between rs2802292 and NAFLD, but the effect is direct (β = 0.10, −0.003 to 0.12 95% C.I., p = 0.04) on diabetes, but only in TT genotypes. Conclusions: The data on our cohort indicate that the longevity-associated FOXO3 variant may have protective effects against diabetes and NAFLD. [ABSTRACT FROM AUTHOR]

Abstract Background The shea tree is a well-known carbon sink in Africa that requires a sustainable conservation of its gene pool. However, the genetic structure of its population is not well studied, especially in Côte d’Ivoire. In this study, 333 superior shea tree genotypes conserved in situ in Côte d’Ivoire were collected and genotyped with the aim of investigating its genetic diversity and population structure to facilitate suitable conservation and support future breeding efforts to adapt to climate change effects. Results A total of 7,559 filtered high-quality single nucleotide polymorphisms (SNPs) were identified using the genotyping by sequencing technology. The gene diversity (HE) ranged between 0.1 to 0.5 with an average of 0.26, while the polymorphism information content (PIC) value ranged between 0.1 to 0.5 with an average of 0.24, indicating a moderate genetic diversity among the studied genotypes. The population structure model classified the 333 genotypes into three genetic groups (GP1, GP2, and GP3). GP1 contained shea trees that mainly originated from the Poro, Tchologo, and Hambol districts, while GP2 and GP3 contained shea trees collected from the Bagoué district. Analysis of molecular variance (AMOVA) identified 55% variance within populations and 45% variance within individuals, indicating a very low genetic differentiation (or very high gene exchange) between these three groups (F ST = 0.004, gene flow Nm = 59.02). Morphologically, GP1 displayed spreading tree growth habit, oval nut shape, higher mean nut weight (10.62 g), wide leaf (limb width = 4.63 cm), and small trunk size (trunk circumference = 133.4 cm). Meanwhile, GP2 and GP3 showed similar morphological characteristics: erect and spreading tree growth habit, ovoid nut shape, lower mean nut weight (GP2: 8.89 g; GP3: 8.36 g), thin leaf (limb width = 4.45 cm), and large trunk size ( GP2: 160.5 cm, GP3: 149.1 cm). A core set of 100 superior shea trees, representing 30% of the original population size and including individuals from all four study districts, was proposed using the “maximum length sub-tree function” in DARwin v. 6.0.21. Conclusion These findings provide new knowledge of the genetic diversity and population structure of Ivorian shea tree genetic resources for the design of effective collection and conservation strategies for the efficient use of inbreeding.

Abstract Cancer ranks as the second leading cause of mortality worldwide, prompting extensive investigations into factors contributing to its development. Among these factors, genetic variations, known as genotypic polymorphisms, have been identified as significant influencers in the susceptibility to various types of cancer. Recent research has focused on exploring the connection between polymorphisms in the Long Non-coding RNA HOTAIR and cancer risk. However, the results from these studies have been inconsistent, leading to ambiguity and controversy. To address this uncertainty, we conducted a systematic analysis by gathering relevant studies from PubMed, EMBASE, and Google Scholar. Specifically, we focused on three well-studied polymorphisms within the HOTAIR lncRNA (HOTAIR rs920778 C > T, HOTAIR rs1899663 G > T, HOTAIR rs4759314 A > G) and their association with cancer risk. Our meta-analysis included data from 48 case–control studies involving 42,321 cases and 54,137 controls. The results of our updated meta-analysis revealed a significant correlation between HOTAIR rs1899663 G > T and HOTAIR rs4759314 A > G polymorphisms and overall cancer risk, particularly in the homozygous and recessive genetic models. Subgroup analysis further revealed that these associations were notably pronounced in the Asian population but not observed in the Iranian population. Furthermore, our findings underscore the potential of HOTAIR polymorphisms as diagnostic markers for overall cancer risk, particularly in gynecological cancers, precisely, HOTAIR rs1899663 G > T polymorphism in breast cancer. In conclusion, our systematic analysis provides compelling evidence that Long Non-coding RNA HOTAIR polymorphisms are linked to cancer risk, particularly in certain populations and cancer types, suggesting their potential clinical relevance as diagnostic indicators.

Summary: Iron‐refractory iron deficiency anaemia (IRIDA) is a rare autosomal recessive disorder, distinguished by hypochromic microcytic anaemia, low transferrin levels and inappropriately elevated hepcidin (HEPC) levels. It is caused by mutations in TMPRSS6 gene. Systematic screening of 500 pregnant women with iron deficiency anaemia having moderate to severe microcytosis with no other causes of anaemia were enrolled to rule out oral iron refractoriness. It identified a final cohort of 10 (2.15% prevalence) individuals with IRIDA phenotype. Haematological and biochemical analysis revealed significant differences between iron responders and iron non‐responders, with iron non‐responders showing lower haemoglobin, red blood cell count, serum iron and serum ferritin levels, along with elevated HEPC (9.47 ± 2.75 ng/mL, p = 0.0009) and erythropoietin (4.58 ± 4.07 µ/mL, p = 0.0196) levels. Genetic sequencing of the TMPRSS6 gene in this final cohort identified 10 novel variants, including seven missense and three frame‐shift mutations, with four missense variants showing high functional impact defining the IRIDA phenotype. Structural analysis revealed significant damage caused by two variants (p.L83R and p.S235R). This study provides valuable insights into IRIDA among pregnant women in the Indian subcontinent, unveiling its underlying causes of unresponsiveness, genetic mechanisms and prevalence. Furthermore, research collaboration is essential to validate these findings and develop effective treatments. [ABSTRACT FROM AUTHOR]

The present distribution of Siberian boreal forests that are dominated by larches (Larix spp.) is influenced, to an unknown extent, by glacial history. Knowing the past treeline dynamics can improve our understanding of future treeline shifts under changing climate. Here, we study patterns in the genetic variability of Siberian Larix to help unravel biogeographic migration routes since the Last Glacial Maximum (LGM). We infer the spatial distribution and the postglacial demographic history of Larix using genome‐wide single nucleotide polymorphisms (SNPs) derived through genotyping by sequencing (GBS) from 130 individuals sampled across eastern Siberia. Our analysis gives statistical support for two or three clusters, spanning from western to eastern Siberia. These clusters reveal a genetic structure influenced by isolation resulting from geographical distance, barriers imposed by geographic features, and distinct glacial histories. Assuming three clusters, our demographic inference indicates that the common ancestor of the current Larix populations existed in northeast Siberia well before the LGM. This suggests that Larix persisted in the northern region throughout previous glacials. Our genetic studies suggest that Larix likely survived the cold LGM in northern refugia, enabling a fast colonization of Siberia. Instead of complete repopulation from southern areas postglacially, the northernmost Larix expansion during the Holocene seems to have benefitted from refugial populations ahead of the treeline. Present‐day migration is expected to be slow initially, due to the absence of current refugial populations in the far north, in contrast to the early‐Holocene situation. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most frequently diagnosed cancer among women worldwide, including Algeria. Certain single nucleotide polymorphisms (SNPs) have been linked to higher risk of BC. Several studies have been performed on the insulin- like growth factor 1 (IGF-1) T > C (rs7136446) and the interleukin 6 (IL-6) 174 G > C (rs1800795) SNPs to explore their role in BC. The aim of this study is to investigate the association between the 2 SNPs, IL-6 (rs1800795) and IGF-1 (rs7136446) with BC in the population of western Algeria. This study was carried out for the first time among the Algerian population. This case-control study included 109 BC patients and 112 healthy controls. Genomic DNA was extracted from peripheral blood samples. DNA concentration was determined using the Qubit 2.0 fluorometer. The genotyping of selected SNPs was performed by real-time polymerase chain reaction followed by statistical analysis to assess genotypic frequencies and genetic association with BC. The results showed that IGF-1 rs7136446 was positively associated with BC (p = 0.00001) and that the distribution of genotype frequencies of rs7136446 showed a statistically difference between human epidermal growth factor receptor 2 (HER-2) positive and HER-2 negative BC (p = 0.04), but this association did not last after the correction of Bonferroni. No association was found in genotype distribution of the IL-6 (rs1800795) among controls and BC patients or with clinicopathological parameters including HER-2 status in BC (p > 0.05). In summary, our findings indicate that IGF-1 rs7136446 is associated with BC in our population of western Algeria. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to reveal the single nucleotide polymorphisms (SNPs) of the bovine Stearoyl-CoA desaturase-1 (SCD1) to explore the correlation between genotypes and carcass, meat quality, adipogenic traits, fatty acid composition, and milk production traits in cattle. Four SNPs, g.21272246 A>G, g.21272306 T>C, g.21272422 C>T, and g.21272529 A>G, were found by Sanger sequencing; further statistical analysis showed that these four SNPs of the SCD1 gene were significantly associated with carcass traits and meat quality, including carcass weight, carcass fat coverage rate, rib eye area, marbling score, adipogenic traits, and fatty acid composition. Additionally, a modest effect on milk production traits, such as average milk yield and milk fat content, was observed in cows. Further haplotype analysis indicated that the combinations of H2H3 and H2H2 of SNPs had a higher value than others. Our results indicate that these four SNPs are potentially effective markers and could be used in marker-assisted breeding to improve meat and milk quality simultaneously in the future. Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in the biosynthesis of monounsaturated fatty acids and is considered a candidate gene for improving milk and meat quality traits. Sanger sequencing was employed to investigate the genetic polymorphism of the fifth exon and intron of bovine SCD1, revealing four SNPs, g.21272246 A>G, g.21272306 T>C, g.21272422 C>T, and g.21272529 A>G. Further variance analysis and multiple comparisons were conducted to examine the relationship between variation sites and economic traits in Chinese Simmental cattle, as well as milk production traits in Holstein cows. The findings revealed these four loci exhibited significant associations with carcass traits (carcass weight, carcass length, backfat thickness, and waist meat thickness), meat quality (pH value, rib eye area, and marbling score), adipogenic traits (fat score and carcass fat coverage rate), and fatty acid composition (linoleic acid and α-linolenic acid). Furthermore, these loci were additionally found to be significantly associated with average milk yield and milk fat content in cows. In addition, a haplotype analysis of combinations of SNPs showed that H2H3 has a significant association with adipogenic traits and H2H2 was associated with higher levels of linoleic acid and α-linolenic acid than the other combinations. These results suggest that the four SNPs are expected to be prospective genetic markers for the above economic traits. In addition, the function of SNPs in exon 5 of SCD1 on gene expression and protein structure needs to be explored in the future. [ABSTRACT FROM AUTHOR]

Background: Previous observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated the causal relationship between cathepsins and cancer using Mendelian randomization (MR) analysis. Methods: We used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis. Results: After correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027–1.114, P = 0.001, PFDR= 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919–0.975, P = 0.0002, PFDR= 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001–1.025, P = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001–1.034, P = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012–1.101, P = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949–0.991, P = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902–0.944, P = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938–0.990, P = 0.006). Conclusion: Our MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer. [ABSTRACT FROM AUTHOR]

Epidemiological studies link COVID-19 to increased cardiac arrest (CA) risk, but causality remains unclear due to potential confounding factors in observational studies . We conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data, employing COVID-19-associated single nucleotide polymorphisms (SNPs) with significance values smaller than 5 × 10⁻⁸. We calculated inverse-variance weighted (IVW) MR estimates and performed sensitivity analyses using MR methods robust to horizontal pleiotropy. Additionally, a reverse MR analysis was conducted using CA-associated SNPs with significance values smaller than 1 × 10⁻⁵. Results indicated that infected COVID-19 (OR = 1.12, 95% CI = 0.47–2.67, p = 0.79), hospitalized COVID-19 (OR = 1.02, 95% CI = 0.70–1.49, p = 0.920), and severe respiratory COVID-19 (OR = 0.99, 95% CI = 0.81–1.21, p = 0.945) did not causally influence CA risk. Reverse MR analysis also did not support a causal effect of CA on COVID-19. Thus, associations in observational studies may stem from shared biological factors or environmental confounding. [ABSTRACT FROM AUTHOR]

Karnal bunt (KB) is a seed and airborne wheat disease caused by the fungus Tilletia indica Mitra. The floret-infecting fungus damages grains and adversely affects wheat quality through the production of trimethylamine. Deployment of host-plant resistance is the best strategy to combat this disease. The present study explored two sources of genetic resistance to KB by developing recombinant inbred lines (RILs) with a common susceptible parent. Munal × WL711 and SAUAL/KIRITTI/SAUL × WL711 produced 275 RILs each which were evaluated for KB disease resistance under four environments. The minimum value for disease incidence was 0% while the maximum values were 8.14% and 10.38% during 2018–2019 and 2019–2020, respectively. This study identified several RILs with durable and heritable resistance against KB, while SAUAL/KIRITTI/SAUL was identified as the highest-performance resistant parent. Based on the best linear unbiased estimates across environments, two bulk populations (resistant and susceptible) were developed from each set of progeny and were subjected to genome-wide single nucleotide polymorphism (SNP) genotyping using a 50K Affymetrix SNP array. Bulked segregation analysis showed that the maximum SNP index was identified on chr2A, chr6A, and chr7A in Munal × WL-711 while it was on chr4B and chr7B in the SAUAL/KIRITTI/SAUL × WL711 population. Taken together, the identified RILs might serve as breeding material for the development of KB-resistant wheat cultivars in the future. [ABSTRACT FROM AUTHOR]

BackgroundGrowing evidence suggests a relationship between gut microbiota composition and breast diseases, although the precise nature of this association remains uncertain. To investigate the causal relationship between gut microbiota and breast diseases, we utilized two-way Mendelian randomization (MR) analysis.MethodsFour common diseases were included as outcomes: breast cancer, breast cysts, inflammatory disorders of the breast, and infections of the breast associated with childbirth, along with their subtypes. Genetic data on gut microbiota were extracted from genome-wide association studies (GWAS). The primary approach used to investigate the association between these genetic factors and gut microbiota was the inverse-variance-weighted (IVW) method with random-effects types. Sensitivity analyses, such as Cochran’s Q test, the MR-Egger intercept test, and leave-one-out analysis, were conducted to ensure the stability and reliability of the MR findings.ResultsWe discovered plausible causal links between 20 microbial categories and the breast diseases, with a significance level of p

ABSTRACT Background Emerging evidence has indicated possible efficacy benefit of platinum‐based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple‐negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results. Materials and Methods Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum‐based neoadjuvant treatment. We prospectively enrolled women with stage IIB‐IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline‐based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease‐free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled. Results The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3‐year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS. Conclusions Platinum‐based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline‐ and taxane‐based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.

Abstract Background Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. Method This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. Discussion Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients.

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Methods: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. Results: We found that rs17069665 (GG vs. AA+AG, adjustedOR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. Conclusions: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis. [ABSTRACT FROM AUTHOR]

The commercially important species Lutjanus campechanus (Northern/Gulf red snapper) and Lutjanus purpureus (Southern/Caribbean red snapper) are the protagonists of a decade's long taxonomic debate over their species delimitation, due in part to partial habitat overlap, extensive morphological similarity, and the lack of resolution when applying canonically reliable DNA barcoding approaches. In this study, we leveraged publicly available RAD-Seq data for L. campechanus and L. purpureus to identify species-informative singlenucleotide polymorphisms (SNPs) at the genome scale that were successful in distinguishing the Northern and Southern red snappers, while also detecting individuals exhibiting introgression. This 4-step empirical approach demonstrates the value of applying novel bioinformatics pipelines to existing genome-scale data to maximize the distillation of informative subsets. Our results facilitate economically relevant species identification in addition to confirming or challenging species identifications for specimens with data in public databases. These findings and their applications will benefit future sustainability strategies and broader research questions surrounding these overfished and evolutionarily entangled snapper species. [ABSTRACT FROM AUTHOR]

With the outbreak of coronavirus disease 2019 (COVID-19), there has been an increasing focus on exploring the relationship between SARS-CoV-2 infection and tumors. However, there is no consensus on the association between COVID-19 and lymphoma. In this study, genome-wide association study (GWAS) summary data sets for COVID-19 and lymphoma were obtained from the OPEN GWAS website. Single nucleotide polymorphisms (SNPs) were selected as genetic instrument variants for fulling P < 5 × 10−8 and linkage disequilibrium [LD] r2 < 0.001. Both palindromic and outlier SNPs were removed. Cochran's Q test, the MR‒Egger intercept test, and leave-one-out analysis were employed to assess the sensitivity of the effect of COVID-19 on lymphoma. The results showed that COVID-19 patients with very severe respiratory symptoms have an increased risk of developing diffuse large B-cell lymphoma (IVW, OR = 1.765, 95% CI 1.174–2.651, P = 0.006). There was no association between COVID-19 with very severe respiratory symptoms and Hodgkin's lymphoma or other types of non-Hodgkin's lymphoma. No horizontal or directional pleiotropy was observed in the Mendelian randomization analysis. In conclusion, SARS-CoV-2 infection with very severe respiratory symptoms may be a potential risk factor for diffuse large B-cell lymphoma (DLBCL), and follow-up studies with larger samples are needed. [ABSTRACT FROM AUTHOR]

Background: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. Methods: We included 112 kidney recipients genotyped for CYP3A5*3, CYP3A4*1.001, and CYP3A4*22. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Results: Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A4*1/*1 (86.6%) and CYP3A5*3/*3 (77.7%) genotypes. CYP3A4*1.001 and CYP3A5*1 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A4*22 allele showed no such effect (p = 0.016, p < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. Conclusions: The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, β = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, β = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, β = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, β = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025–234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways. [ABSTRACT FROM AUTHOR]

Background: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for the genetic elements shared between PCOS and depression. Methods: Differentially expressed genes (DEGs) were screened out through GEO2R using the PCOS and depression datasets in NCBI. Protein–protein interaction (PPI) network analysis and enrichment analysis were performed to identify the potential hub genes. After verification using other PCOS and depression datasets, the associations between key gene polymorphism and comorbidity were further studied using data from the UK biobank (UKB) database. Results: In this study, three key genes, namely, SNAP23, VTI1A, and PRKAR1A, and their related SNARE interactions in the vesicular transport pathway were identified in the comorbidity of PCOS and depression. The rs112568544 at SNAP23, rs11077579 and rs4458066 at PRKAR1A, and rs10885349 at VTI1A might be the genetic basis of this comorbidity. Conclusions: Our study suggests that the SNAP23, PRKAR1A, and VTI1A genes can directly or indirectly participate in the imbalanced assembly of SNAREs in the pathogenesis of the comorbidity of PCOS and depression. These findings may provide new strategies in diagnosis and therapy for this comorbidity. [ABSTRACT FROM AUTHOR]

Background: Single nucleotide polymorphisms (SNPs), as the most abundant form of DNA variation in the human genome, contribute to age-related cataracts (ARC) development. Apoptosis of lens epithelial cells (LECs) is closely related to ARC formation. Insulin-like growth factor 1 (IGF1) contributes to cell apoptosis regulation. Moreover, IGF1 was indicated to exhibit a close association with cataract formation. Afterward, an investigation was conducted to examine the correlation between polymorphisms in IGF1 and the susceptibility to ARC. Methods: The present investigation was a case-control study. Venous blood draws were collected from the participants for DNA genotyping. Lens capsule samples were collected to detect mRNA and apoptosis. TaqMan RT-PCR was used to detect IGF1 polymorphism genotypes and qRT PCR was used to detect IGF1 mRNA levels in LECs. LEC apoptosis was evaluated through flow cytometry. The chi-square test was used to compare differences between ARCs and controls of each SNP. Results: We found that the G allele frequency in the IGF1-rs6218 was higher in the ARCs than in the controls. Furthermore, it was observed that the rs6218 GG genotype exhibited a positive correlation to elevated levels of IGF1 mRNA in LECs. The IGF1 mRNA in the LECs and the apoptosis of LECs in nuclear type of ARCs (ARNC) was higher than the controls. Conclusion: The susceptibility to ARC was related to IGF1-rs6218 polymorphism, and this polymorphism is associated with IGF1 expression at the mRNA level. Moreover, apoptosis in LECs of ARNCs was found to be increased. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. Method: This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. Discussion: Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. IKZF3 (IKAROS family zinc finger 3) is a hematopoietic‐specific transcription factor, and it has been validated that it is involved in leukemia. However, the role of IKZF3 single‐nucleotide polymorphisms (SNPs) remains unclear. In this case–control study, the authors investigated the association of IKZF3 SNPs with ALL in children. Methods: Six IKZF3 reference SNPs (rs9635726, rs2060941, rs907092, rs12946510, rs1453559, and rs62066988) were genotyped in 692 patients who had ALL (cases) and in 926 controls. The associations between IKZF3 polymorphisms and ALL risk were determined using odds ratios (ORs) and 95% confidence intervals (CIs). The associations of rs9635726 and rs2060941 with the risk of ALL were further estimated by using false‐positive report probability (FPRP) analysis. Functional analysis in silico was performed to evaluate the probability that rs9635726 and rs2060941 might influence the regulation of IKZF3. Results: The authors observed that rs9635726C>T (adjusted OR, 1.49; 95% CI, 1.06–2.11; p =.023) and rs2060941G>T (adjusted OR, 1.51; 95% CI, 1.24–1.84; p =.001) were related to and increased risk of ALL in the recessive and dominant models, respectively. Furthermore, the associations of both rs9635726 (FPRP =.177) and rs2060941 (FPRP <.001) with ALL were noteworthy in the FPRP analysis. Functional analysis indicated that rs9635726 and rs2060941 might repress the transcription of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. Conclusions: This study revealed that IKZF3 polymorphisms were associated with increased ALL susceptibility in children and might influence the expression of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. IKZF3 polymorphisms were suggested as a biomarker for childhood ALL. [ABSTRACT FROM AUTHOR]

Jute (Corchorus sp.), a commercially important and eco-friendly crop, is widely cultivated in Bangladesh, India, and China. Some varieties of this tropical plant such as the Corchorus olitorius. Variety accession no. 2015 (acc. 2015) has been found to be low-temperature tolerant. The current study was designed to explore the genome-wide variations present in the tolerant plant acc. 2015 in comparison to the sensitive farmer popular variety Corchorus olitorius var. O9897 using the whole genome resequencing technique. Among different variations, intergenic Single Nucleotide Polymorphism (SNPs) and Insertion-Deletion (InDels) were found in the highest percentage whereas approximately 3% SNPs and 2% InDels were found in exonic regions in both plants. Gene enrichment analysis indicated the presence of acc. 2015 specific SNPs in the genes encoding peroxidase, ER lumen protein retaining receptor, and hexosyltransferase involved in stress response (GO:0006950) which were not present in sensitive variety O9897. Besides, distinctive copy number variation regions (CNVRs) comprising 120 gene loci were found in acc. 2015 with a gain of function from multiple copy numbers but absent in O9897. Gene ontology analysis revealed these gene loci to possess different receptors like kinases, helicases, phosphatases, transcription factors especially Myb transcription factors, regulatory proteins containing different binding domains, annexin, laccase, acyl carrier protein, potassium transporter, and vesicular transporter proteins that are responsible for low temperature induced adaptation pathways in plants. This work of identifying genomic variations linked to cold stress tolerance traits will help to develop successful markers that will pave the way to develop genetically modified cold-resistant jute lines for year-round cultivation to meet the demand for a sustainable fiber crop economy.

Abstract Osteosarcoma (OS) is the most common type of primary bone malignancy. Common genetic variants including single nucleotide polymorphisms (SNPs) have been associated with osteosarcoma risk, however, the results of published studies are inconsistent. The aim of this study was to systematically review genetic association studies to identify SNPs associated with osteosarcoma risk and the effect of race on these associations. We searched the Medline, Embase, Scopus from inception to the end of 2019. Seventy-five articles were eligible for inclusion. These studies investigated the association of 190 SNPs across 79 genes with osteosarcoma, 18 SNPs were associated with the risk of osteosarcoma in the main analysis or in subgroup analysis. Subgroup analysis displayed conflicting effects between Asians and Caucasians. Our review comprehensively summarized the results of published studies investigating the association of genetic variants with osteosarcoma susceptibility, however, their potential value should be confirmed in larger cohorts in different ethnicities.

Alzheimer's disease (AD) is the leading cause of dementia globally and one of the most serious future healthcare issue. AD is expected to rise from 27 million to 106 million cases in the next four decades impacting one in every 85 people on the planet. For the existing healthcare systems, the most frequent kind of dementia is a significant source of worry. AD usually refers to Untreated Schizophrenia, a degenerative neurological disorder defined by memory loss and disorientation. AD is the world's third greatest cause of mortality, after only heart disease and cancer. It has surpassed cancer as the most dreaded disease on the planet. AD is catastrophic in the long-term run since it slowly but gradually destroys the body's cells. A variety of efforts have been made to employ structural Magnetic Resonance Imaging (MRI) modalities to differentiate between people with AD and their healthy counterparts. These have also been examined as deep learning algorithms for the categorization of MRI data. It is difficult to find patients with modest cognitive decline who may acquire Alzheimer's. As a result, creating deep learning-based disease detection techniques to assist clinicians in detecting prospective Alzheimer's patients is crucial. The performance comparison of the Imaging, Electronic Health Record (EHR), and Single Nucleotide Polymorphisms (SNP) datasets are evaluated using the metrics Accuracy, Sensitivity, Specificity, and Multi Area. Different mistakes are added under the curves for gradient calculation. The research results are as follows: based on standard datasets the results show that the proposed feature selection algorithms discover a sub-optimal minimal level feature set from a larger input feature set for diagnosing Alzheimer's disease, with higher values for system performance in terms of Accuracy as well as losses against training and Accuracy and losses against validation. These results can demonstrate the model's suitability for the purpose. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common type of primary bone malignancy. Common genetic variants including single nucleotide polymorphisms (SNPs) have been associated with osteosarcoma risk, however, the results of published studies are inconsistent. The aim of this study was to systematically review genetic association studies to identify SNPs associated with osteosarcoma risk and the effect of race on these associations. We searched the Medline, Embase, Scopus from inception to the end of 2019. Seventy-five articles were eligible for inclusion. These studies investigated the association of 190 SNPs across 79 genes with osteosarcoma, 18 SNPs were associated with the risk of osteosarcoma in the main analysis or in subgroup analysis. Subgroup analysis displayed conflicting effects between Asians and Caucasians. Our review comprehensively summarized the results of published studies investigating the association of genetic variants with osteosarcoma susceptibility, however, their potential value should be confirmed in larger cohorts in different ethnicities. [ABSTRACT FROM AUTHOR]

Background: The ubiquitin ligase HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 is essential for the establishment and maintenance of spermatogonia. However, the role of HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 in regulating germ cell differentiation remains unclear, and clinical evidence linking HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 to male infertility pathogenesis is lacking. Objective: This study aims to investigate the role of HUWE1 in germ cell differentiation and the mechanism by which a HUWE1 single nucleotide polymorphism increases male infertility risk. Materials and methods: We analyzed HUWE1 single nucleotide polymorphisms in 190 non‐obstructive azoospermia patients of Han Chinese descent. We evaluated HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 regulation by retinoic acid receptor alpha using chromatin immunoprecipitation assays, electrophoretic mobility shift assays, and siRNA‐mediated RARα knockdown. Using C18‐4 spermatogonial cells, we determined whether HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 participated in retinoic acid‐mediated retinoic acid receptor alpha signaling. We performed luciferase assays, cell counting kit‐8 assays, immunofluorescence, quantitative real‐time polymerase chain reaction, and western blotting. We quantified HUWE1 and retinoic acid receptor alpha in testicular biopsies from non‐obstructive azoospermia and obstructive azoospermia patients using quantitative real‐time polymerase chain reaction and immunofluorescence. Results: Three HUWE1 single nucleotide polymorphisms were significantly associated with spermatogenic failure in 190 non‐obstructive azoospermia patients; one (rs34492591) was in the HUWE1 promoter. Retinoic acid receptor alpha regulates HUWE1 gene expression by binding to its promoter. HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 participates in retinoic acid/retinoic acid receptor alpha signaling pathway and regulates the expression of germ cell differentiation genes STRA8 and SCP3 to inhibit cell proliferation and reduce γH2AX accumulation. Notably, significantly lower levels of HUWE1 and RARα were detected in testicular biopsy samples from non‐obstructive azoospermia patients. Conclusions: An HUWE1 promoter single nucleotide polymorphism significantly downregulates its expression in non‐obstructive azoospermia patients. Mechanistically, HECT, UBA, and WWE domain‐containing E3 ubiquitin protein ligase 1 regulates germ cell differentiation during meiotic prophase through its participation in retinoic acid/retinoic acid receptor alpha signaling and subsequent modulation of γH2AX. Taken together, these results strongly suggest that the genetic polymorphisms of HUWE1 are closely related to spermatogenesis and non‐obstructive azoospermia pathogenesis. [ABSTRACT FROM AUTHOR]

Lumpy skin disease virus (LSDV) has recently undergone rapid spread, now being reported from more than 80 countries, affecting predominantly cattle and to a lesser extent, water buffalo. This poxvirus was previously considered to be highly host-range restricted. However, there is an increasing number of published reports on the detection of the virus from different game animal species. The virus has not only been shown to infect a wide range of game species under experimental conditions, but has also been naturally detected in oryx, giraffe, camels and gazelle. In addition, clinical lumpy skin disease has previously been described in springbok (Antidorcas marsupialis), an African antelope species, in South Africa. This report describes the characterization of lumpy skin disease virus belonging to cluster 1.2, from field samples from springbok, impala (Aepyceros melampus) and a giraffe (Giraffa camelopardalis) in South Africa using PCR, Sanger and whole genome sequencing. Most of these samples were submitted from wild animals in nature reserves or game parks, indicating that the disease is not restricted to captive-bred animals on game farms or zoological gardens. The potential role of wildlife species in the transmission and maintenance of LSDV is further discussed and requires continuing investigation, as the virus and disease may pose a serious threat to endangered species. [ABSTRACT FROM AUTHOR]

Objective: Studies of Wnt variants-related to bone resorption in periodontitis are limited. The aim of this study was to establish the genotype and allele frequency of gene variants associated with the Wnt pathway in systemically healthy individuals with and without periodontitis (PD). Materials and methods: One hundred fifty-seven systemically healthy individuals were evaluated, 90 with PD and 67 without PD. Periodontal clinical indexes, serological and clinical indices of inflammation, and the following variants associated with the Wnt pathway: DKK, SOST, LRP5, and KREMEN were analyzed by high resolution melting and confirmed by Sanger sequencing. Results: In the PD-free group, 67.2% of the individuals presented the variant for DKKrs1896367 (p = 0.008) and 82.6% had the variant for KREMEN rs132274 (p = 0.016). The heterozygous variant for the DKK rs1896367 polymorphism was associated with the absence of PD and lower severity OR: 0.33 (CI95% 0.15–0.70) and OR: 0.24 (CI95% 0.11–0.53), respectively. Similarly, KREMEN rs132274 was the homozygous variant associated with the absence of PD (OR: 0.33 (CI95% 0.13–0.88)). On the contrary, 85.6% of individuals with PD presented a variant for DKK rs1896368 (p = 0.042), all suffering severe forms of periodontitis. Conclusion: The presence of DKKrs1896367 and KREMENrs132274 variants in individuals without PD suggests that these single nucleotide polymorphisms could be protective factors for bone loss in PD. A very interesting finding is that the DKKrs1896368 variant was found in a high percentage of severe cases, suggesting that the presence of this variant may be related to the severe bone loss observed in PD. [ABSTRACT FROM AUTHOR]

Background: This comprehensive molecular study investigates the genetic variations in individuals residing at different altitudes in West Saudi Arabia, specifically contrasting sea-level residents in Jeddah (SL) with high-altitude dwellers in Taif (HA). The study focuses on the significant role of genetic adaptations in response to environmental challenges, particularly hypoxia. Understanding these genetic differences according to geographical location is crucial for multiple reasons. It not only sheds light on the adaptive mechanisms that humans develop in response to environmental stressors like reduced oxygen levels but also has broader implications for medical, anthropological, and evolutionary studies. By exploring how distinct populations adapt to their environments, this research provides valuable insights into the complex interplay between genetics, health, and disease, highlighting the importance of considering genetic diversity in medical and genetic research. Methods: The research involved amplifying and sequencing three pivotal genes associated with hypoxia adaptation: Hif-1a, VEGFa, and VHL. Advanced genomic techniques were utilized to analyze samples from 22 volunteers, 10 from the sea level region of Jeddah and 12 from the high-altitude region of Taif. The study aimed to identify and analyze single nucleotide polymorphisms (SNPs) in these genes and their implications in altitude adaptation. Results: Distinct SNPs were identified in the Hif-1a, VEGFa, and VHL genes, with high-altitude residents displaying more pronounced variations. The phylogenetic analysis demonstrated clear genetic clustering based on altitude, highlighting the molecular adaptations induced by altitude variations. The study reveals a complex interplay between genetics and environmental conditions, significantly contributing to our understanding of human adaptation to high altitudes. Conclusion: This research underscores the profound impact of altitude on human genetics. The findings provide critical insights into how genetic variations facilitate adaptation to challenging environmental conditions, such as hypoxia, encountered at high altitudes. These insights have broad implications, potentially informing medical research related to altitude sickness and other altitude-related health issues. [ABSTRACT FROM AUTHOR]

Infertility is defined as failure to achieve a clinical pregnancy after 12 months of unprotected intercourse. It affects 15% of couples globally and 22% of couples within Pakistan. Female infertility can be caused by numerous genetic or environmental factors including hormone imbalances and exposure to chemicals or radiation. The prevalence of vitamin D deficiency among the adult population was reported to be 14–59% with a higher prevalence in Asian countries. Furthermore, the expression of Vitamin D receptor (VDR) can play a vital role in the reproductive organs of females. Hence, the aim of our present study was to check the association of VDR polymorphisms with infertile females. For this purpose, blood samples were collected for genotyping of four known VDR mutations [FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232), and BsmI (rs1544410)] via PCR-based RFLP assay. Genotyping indicated that FokI, TaqI, and ApaI are associated with infertility (p = 0.004*, p = 0.013*, and p = 0.033*, respectively). However, BsmI did not show any significance. Multinomial regression analysis indicated that FokI heterozygous genotypes increase the risk of infertility by 2.5 times (hetero: OR = 2.5, 95%, p = 0.001*) as compared to wild type. Heterozygous genotypes of TaqI and ApaI were found to play a protective role and reduce the risk of infertility by 58 and 52%, respectively [TaqI: OR = 0.42, 95%, p = 0.004*, ApaI: OR = 0.48, 95%, p = 0.01*, respectively] as compared to wild type. Multinomial logistic regression analysis was also performed for allelic data as well. Thus, it could be summarized that among the studied polymorphisms of VDR, FokI SNP greatly increased the risk of infertility, while TaqI and ApaI genotypes protect from infertility. However, BsmI does not influence the risk of infertility in Pakistani females. [ABSTRACT FROM AUTHOR]

American ginseng (Panax quinquefolius) is widely used due to its medicinal properties. Ontario is a major producer of cultivated American ginseng, where seeds were originally collected from the wild without any subsequent scientific selection, and thus the crop is potentially very diverse. A collection of 162 American ginseng plants was harvested from a small area in a commercial garden and phenotyped for morphological traits, such as root grade, stem length, and fresh and dry weights of roots, leaves, stems, and seeds. All of the traits showed a range of values, and correlations were observed between root and stem weights, root dry weight and leaf dry weight, as well as root and leaf fresh weights. The plants were also genotyped using single nucleotide polymorphisms (SNPs) at the PW16 locus. SNP analysis revealed 22 groups based on sequence relatedness with some groups showing no SNPs and others being more diverse. The SNP groups correlated with significant differences in some traits, such as stem length and leaf weight. This study provides insights into the genetic and phenotypic diversity of cultivated American ginseng grown under similar environmental conditions, and the relationship between different phenotypes, as well as genotype and phenotype, will aid in future selection programs to develop American ginseng cultivars with desirable agronomic traits. [ABSTRACT FROM AUTHOR]

The utilization of high-throughput data sequencing has been instrumental in the generation of extensive datasets derived from diverse studies, with a primary focus on elements such as epigenetics, genomic variations, genome-wide associations, and differential gene expression in the context of bull fertility. However, the task of achieving effective prediction remains a formidable challenge. The current investigation aims to examine variations identified through RNA-Seq, with a particular emphasis on coding region alterations, and subsequently, map these variations to the region of genes associated with fertility functions and proximity. In this study, transcriptome analysis was carried over sperm samples obtained from 12 bulls, half of which exhibited high fertility (n=6) and the other half low fertility (n=6) based on their conception rates. Bioinformatics tools align the data; genetic variants were identified and mapped subsequently to known fertility quantitative trait loci (QTL). After filtering for fertility-specific single nucleotide polymorphisms (SNPs) with missense mutations, we identified a total of six significant biomarkers. This research demonstrates the efficacy of our innovative approach for screening genetic variants, ultimately leading to the identification of fertility markers within bovine spermatozoa. [ABSTRACT FROM AUTHOR]

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive and recurrent soft tissue sarcoma. It most commonly occurs secondary to neurofibromatosis type I, and it has a 5-year survival rate of only 8–13%. To better study the tumor heterogeneity of MPNST and to develop diverse treatment options, more tumor-derived cell lines are needed to obtain richer biological information. Here, we established a primary cell line of relapsed MPNST RsNF cells derived from a patient diagnosed with NF1 and detected the presence of NF1 mutations and SUZ12 somatic mutations through whole-exome sequencing(WES). Through tumor molecular marker targeted sequencing and single-cell transcriptome sequencing, it was found that chromosome 7 copy number variation (CNV) was gained in this cell line, and ZNF804B, EGFR, etc., were overexpressed on chromosome 7. Therefore, RsNF cells can be used as a useful tool in NF1-associated MPNST genomic amplification studies and to develop new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Low temperature and cold damage are natural factors that seriously reduce wheat yield. Thus, how to improve the cold resistance of wheat has been the focus of wheat breeders and geneticists. However, the genetic improvement for this trait has been slow, mainly because cold resistance is a complex quantitative trait and field phenotypic identification is relatively difficult. Therefore, the discovery, mapping, and cloning of the cold resistance genes of wheat provide a theoretical basis for the genetic improvement of wheat against cold resistance and facilitate the analysis of the molecular mechanisms of cold resistance in wheat. This study used the wheat line H261 and its EMS mutants LF2099 and XiNong 239 as materials. Cold trait segregation occurred in the F2 generation of mutants LF2099 and XiNong 239 at a 15:1 separation ratio. Genetic analysis showed that two dominant overlapping genes, temporarily named Wcr-3 and Wcr-4, control cold resistance in wheat. Furthermore, a combined BSA and SNP array established that Wcr-3 is between BU100519 (SSR marker) and AX-94843669 (SNP marker). The markers are 1.32 cM apart, corresponding to the 5.41 Mb physical interval on the Chinese Spring 2B chromosome with 67 functionally annotated genes. Wcr-4 is located between AX-94657955 (SNP marker) and LC-23 (SSR marker), which are 1.79 cM apart, corresponding to a 2.35 Mb physical interval on the Chinese Spring 2D chromosome, which contains 66 functionally annotated genes. Wcr-3 and Wcr-4 are two new cold resistance genes, laying the foundation for their fine mapping and cloning. [ABSTRACT FROM AUTHOR]

Horses were domesticated later than other farm animals. Horse breeds have been selectively developed by humans to satisfy different needs and purposes. The factory and indigenous breeds are of particular interest, having been bred in purity for many centuries without the addition of foreign blood. Data from 31 stud farms, as well as ranches, located in fifteen regions of the Russian Federation were used in this work. DNA was sampled from 102 stallions of 11 breeds: Arabian, Akhal-Teke, Don, Orlov Trotter, Vladimir Heavy Draft, Russian Heavy Draft, Soviet Heavy Draft, Kabardin, Yakut, Tuva, and Vyatka. Data on the origin of each animal from which the material was collected were taken into account. DNA genotyping was carried out using GGP Equine 70 k ® array chips (Thermo Fisher Scientific, USA). Genetic diversity of horse breeds was estimated using Admixture 1.3. and PLINK 1.9 software. FROH inbreeding was computed via the R detectRUNS package. The minimum length for ROH was set at 1 Mb to reduce the occurrence of false positives. We conducted PCA analysis using PLINK 1.9, and used the ggplot2 library in R for visualizing the results. Indigenous equine breeds, such as Vyatka, Tuva, and Yakut, are very hardy, and well adapted to local environmental and climatic conditions. They are employed as draft power, as well as for milk and meat. Both the Akhal-Teke breed and the Arabian breed have retained a minimum effective population size over many generations. We note significant accumulations of homozygosity in these breeds. In equestrian sports, performance is a top priority. ADMIXTURE and PCA analyses showed similarities between Don equine breeds and Kabardin, as well as some Arabian breed animals. Earlier research indicated the presence of thoroughbred traits in Don stallions. The Orlov Trotter breed stands out as a separate cluster in the structural and PCA analyses. Considering the small population size of this breed, our study found high FROH in all tested animals. The general reduction in the diversity of the horse breed gene pool, due to numerous crosses for breed improvement with thoroughbreds, has lead to a decline in the differences between the top sporting breeds. Our study presents new opportunities for exploring the genetic factors that influence the formation of adaptive traits in indigenous breeds, and for finding ways to preserve genetic diversity for effective population reproduction. [ABSTRACT FROM AUTHOR]

Background: Unimpaired kidney function is important for maintaining a healthy state of homeostasis in the body. A genome-wide association study (GWAS) conducted on kidney function-associated traits and novel loci of Japanese subjects found that insulin-like-growth factor 1 receptor (IGF1R) gene variants associated with replication were responsible for all three kinds of kidney functions and satisfied the Bonferroni significance level. Objective: This study aimed to investigate whether a comparable relationship exists in the Korean population. Method: This study replicated three SNPs (rs28657002, rs10794486, and rs4966025) and conducted a linear regression analysis between 46 SNPs in the IGF1R gene and three kidney function-related traits, namely blood urea nitrogen (BUN), creatinine, and estimated glomerular filtration rate (eGFR) in Koreans. Results: The IGF1R gene was found to be replicated with a significant correlation in Koreans and was extended to the entire gene region to confirm its association with kidney-related functions. Three SNPs in IGF1R were replicated (rs28657002, BUN, P = 3.39 × 10–4; rs10794486, creatinine, P = 5.79 × 10–6; rs4966025, eGFR, P = 1.57 × 10–5) and five SNPs (rs28657002, rs10794486, rs4966025, rs12439557, and rs11247372) showed common significance among the three traits. Additionally, two significant SNPs (rs11857366 and rs28657002) showed the potential to affect IGF1R expression. Conclusions: The results suggest that genetic polymorphisms in the IGF1R replicated previous studies and could affect kidney function. The results of this study will further enhance our understanding of how genetic differences in individuals affect kidney function-related traits. [ABSTRACT FROM AUTHOR]

The commercially important species Lutjanus campechanus (Northern/Gulf red snapper) and Lutjanus purpureus (Southern/Caribbean red snapper) are the protagonists of a decade’s long taxonomic debate over their species delimitation, due in part to partial habitat overlap, extensive morphological similarity, and the lack of resolution when applying canonically reliable DNA barcoding approaches. In this study, we leveraged publicly available RAD-Seq data for L. campechanus and L. purpureus to identify species-informative single‐nucleotide polymorphisms (SNPs) at the genome scale that were successful in distinguishing the Northern and Southern red snappers, while also detecting individuals exhibiting introgression. This 4-step empirical approach demonstrates the value of applying novel bioinformatics pipelines to existing genome-scale data to maximize the distillation of informative subsets. Our results facilitate economically relevant species identification in addition to confirming or challenging species identifications for specimens with data in public databases. These findings and their applications will benefit future sustainability strategies and broader research questions surrounding these overfished and evolutionarily entangled snapper species.

Aims: Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods: PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results: A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion: Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614.