Differences In Allele Frequencies Research Articles

Patterns of genetic variation and local adaptation of a native herbivore to a lethal invasive plant.

Understanding the evolutionary processes that influence fitness is critical to predicting species' responses to selection. Interactions among evolutionary processes including gene flow, drift and the strength of selection can lead to either local adaptation or maladaptation, especially in heterogenous landscapes. Populations experiencing novel environments or resources are ideal for understanding the mechanisms underlying adaptation or maladaptation, specifically in locally co-evolved interactions. We used the interaction between a native herbivore that oviposits on a patchily distributed introduced plant that in turn causes significant mortality to the larvae to test for signatures of local adaptation in areas where the two co-occurred. We used whole-genome sequencing to explore population structure, patterns of gene flow and signatures of local adaptation. We found signatures of local adaptation in response to the introduced plant in the absence of strong population structure with no genetic differentiation and low genetic variation. Additionally, we found localized allele frequency differences within a single population between habitats with and without the lethal plant, highlighting the effects of strong selection. Finally, we identified that selection was acting on larval ability to feed on the plant rather than on females' ability to avoid oviposition, thus uncovering the specific ontogenetic target of selection. Our work highlights the potential for adaptation to occur in a fine-grained landscape in the presence of gene flow and low genetic variation.

Association between polymorphisms of IL33 and IL37 and atopic dermatitis

Atopic dermatitis (AD) is a chronic recurrent inflammatory disease accompanied by severe itching. One of the leading mechanisms underlying the development of AD is an imbalance of the Th1/Th2 cells immune response, which leads to an increased production of inflammatory mediators, including IL-1 family. The IL-1 family includes the recently discovered IL-33 and IL-37, and their role in the pathogenesis of AD has been actively studied. IL-33 functions as an alarmin that can induce IL-31 production, thereby leading to skin barrier impairment, pruritus and scratching. Having both immunomodulatory and immunosuppressive properties, IL-37 suppresses leukocyte infiltration of the affected skin and reduces the activity of proinflammatory cytokines. The aim of our study was to search for associations between gene polymorphisms of IL33, IL37 genes, and risk of AD. A total of 98 patients with moderate and severe AD were included in the study. The control group included 72 healthy volunteers. Polymorphic markers were determined in peripheral blood. After extraction of total RNA, polymorphic markers rs7019575 in the IL33 gene, rs3811046 and rs3811047 in the IL37 gene were analyzed using RT-PCR. There was no statistically significant difference in allele frequency and genotype distribution of rs7019575 (IL33) and rs3811047 (IL37). Studying the rs3811046 polymorphic marker in the IL37 gene showed that the risk of AD was almost 2 times lower for the G allele carriers and more than 2-fold higher for TT homozygous carriers. The haplotype analysis revealed that the GTAA and TTGG haplotypes of IL37 were associated with AD, thus increasing the risk of AD development by 2 and 10 times, respectively. In conclusion, SNP markers identified in this study can be used to predict the risk of AD development in the subjects with a positive family history of atopic diseases.

The Association of Leptin Receptor Gene Q223R Polymorphism with Obesity in the Yakut Population

Background: This study aimed to compare the frequencies of alleles and genotypes of the LEPR Q223R SNP in the Yakut population in samples with normal BMI and obesity and compare the data obtained with other populations worldwide. Methods and Results: The study included 336 DNA samples from volunteers of Yakut nationality (117 women and 219 men) without chronic diseases, whose average age was 47.4±0.06 years. All volunteers were divided into two groups: Group 1 (n=151) with normal BMI and Group 2 (n=185) with obesity. Group 2 was divided into two subgroups: Group 2A (n=156) with BMI ≥30 kg/m2 plus OA and Group 2B (n=29) with BMI ≥30 kg/m2 and without abdominal obesity.The study of the LEPR Q223R SNP was performed using the PCR-RFLP method. The frequency of the G allele of the LEPR Q223R SNP was 79.5% in Group 1 and 82.7% in Group 2. Analysis showed a high frequency of genotype GG: 64.2% and 69.7% in Group 1 and Group 2, respectively. The frequency of the GA genotype was 30.5% in Group 1 and 25.9% in Group 2.The frequency of alleles and genotypes does not differ in the sample of Yakuts with normal BMI and those with obesity. There are also no differences in the frequency of alleles and genotypes based on gender and the presence of abdominal obesity.The high frequency of the G allele in the Yakut population is close to that observed in East Asian populations (86.9%). There was no statistical difference in allele frequencies in comparison with the populations of Han Chinese from Beijing, Japanese from Tokyo, and Vietnamese from Ho Chi Minh City. In European, African, American, and South Asian populations, the G allele occurs with a frequency of 43.7% to 59.2%. Conclusion: The LEPR Q223R SNP does not affect BMI in the Yakut population. In this study, Q223R allele frequencies were like allele frequencies in East Asian populations but not in Caucasians, reflecting racial diversity in the allele distribution of this polymorphism.

Expected values for the accuracy of predicted breeding values accounting for genetic differences between reference and target populations

BackgroundGenetic merit, or breeding values as referred to in livestock and crop breeding programs, is one of the keys to the successful selection of animals in commercial farming systems. The developments in statistical methods during the twentieth century and single nucleotide polymorphism (SNP) chip technologies in the twenty-first century have revolutionized agricultural production, by allowing highly accurate predictions of breeding values for selection candidates at a very early age. Nonetheless, for many breeding populations, realized accuracies of predicted breeding values (PBV) remain below the theoretical maximum, even when the reference population is sufficiently large, and SNPs included in the model are in sufficient linkage disequilibrium (LD) with the quantitative trait locus (QTL). This is particularly noticeable over generations, as we observe the so-called erosion of the effects of SNPs due to recombinations, accompanied by the erosion of the accuracy of prediction. While accurately quantifying the erosion at the individual SNP level is a difficult and unresolved task, quantifying the erosion of the accuracy of prediction is a more tractable problem. In this paper, we describe a method that uses the relationship between reference and target populations to calculate expected values for the accuracies of predicted breeding values for non-phenotyped individuals accounting for erosion. The accuracy of the expected values was evaluated through simulations, and a further evaluation was performed on real data.ResultsUsing simulations, we empirically confirmed that our expected values for the accuracy of PBV accounting for erosion were able to correctly determine the prediction accuracy of breeding values for non-phenotyped individuals. When comparing the expected to the realized accuracies of PBV with real data, only one out of the four traits evaluated presented accuracies that were significantly higher than the expected, approaching h2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sqrt{{{\ ext{h}}}^{2}}$$\\end{document}.ConclusionsWe defined an index of genetic correlation between reference and target populations, which summarizes the expected overall erosion due to differences in allele frequencies and LD patterns between populations. We used this correlation along with a trait’s heritability to derive expected values for the accuracy (R\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{R}}$$\\end{document}) of PBV accounting for the erosion, and demonstrated that our derived ER|erosion\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{E}}\\left[{\ ext{R}}|{\ ext{erosion}}\\right]$$\\end{document} is a reliable metric.

Urbanization and distance shape population structure in Fundulus heteroclitus

Abstract The federal Superfund site at New Bedford Harbor (Massachusetts, USA) is an example of an environment where pollution levels rose quickly and dramatically. Industrial waste containing polychlorinated biphenyls, heavy metals, and other organic pollutants was dumped into the harbor in the mid-20th century. The mummichog (Fundulus heteroclitus) is a widely distributed fish typically susceptible to polychlorinated biphenyl toxicity. However, the population in New Bedford Harbor is one of several that have evolved the ability to tolerate this category of toxicants. Constituents of the aryl hydrocarbon receptor system are linked to this adaptive pollution tolerance. Our population genetic analysis of 444 mummichogs from Massachusetts and Rhode Island estuaries using 55 SNP loci suggests that F. heteroclitus near New Bedford Harbor have large populations and restricted but meaningful levels of gene exchange among adjacent habitats. When comparing polluted to cleaner sites, we find strong evidence of genetic differentiation at a small geographic scale. Populations at the two most polluted sites form a genetically distinct cluster. Much of this differentiation is driven by allele frequency differences at loci associated with the aryl hydrocarbon receptor system. While allele frequencies at loci associated with pollution tolerance vary between clean and polluted habitats, putatively adaptive alleles are present at low frequency elsewhere in our study area.

Research on the Correlation Between rs2110385 Polymorphisms of the Visfatin Gene and Nonproliferative Diabetic Retinopathy

Objective: To investigate the association between rs2110385 polymorphisms of the visfatin gene and the risk of type 2 diabetic retinopathy (DR). Methods: 172 Han subjects were selected from Xi’an Shaanxi Province；140 patients with type 2 diabetes mellitus (T2DM) and 32 normal controls (NC) were selected from our hospital. Patients with diabetes were divided into a non-DR group (T2DM) (n = 69) and a nonproliferative diabetic retinopathy Group (DR) (n =71) after dilated fundus photography and fundus fluorescein angiography. rs2110385/Alu Ⅰ genotypes were detected by standardized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the differences in the detection rates of different genotypes in the above populations were compared. Results: 1) The visfatin level in the DR Group was significantly higher than that in the NC and T2DM groups (P < 0.05). 2) The frequency of GG genotype and G allele of rs2110385 in the DR Group were higher than those in the T2DM and NC groups (80.3, 69.6, 50.0, 86.6, 79, 65.6, P < 0.05). 3) There were significant differences in allele frequency and genotype frequency distribution of rs2110385 between the DR Group and the NC group (P < 0.01). Conclusion: Visfatin increased in the nonproliferative diabetic retinopathy group and could be a potential indicator for the clinical prediction of DR. The G allele of the rs2110385 polymorphic site may be related to the risk of DR.

Abstract A016: The breast cancer genome and its association with the breast tissue bacteriome

Abstract BC is the most prevalent and leading fatal cancer type in women, yet the causes of most cases are unknown, indicating the necessity of deciphering contributing factors to quicken detection and inform therapeutic options. This research explores the relationship between the breast cancer (BC) genome and breast tissue bacteriome. BC forms in microenvironments in which genes and bacteria are in close proximity and research evidences gene-bacteria communication, but the relationship between the BC genome and the changing breast tissue bacteriome is not well understood. We hypothesized that genetic variation in the top ten genes commonly linked to BC: BRCA1, BRCA2, PTEN, TP53, PALB2, CHEK2, ATM, BRIP1, BARD1 , and STK11 would be associated with variations in the breast tissue bacteriome. We conducted 30X whole genome sequencing on 60 breast tissue samples (healthy, H (n=15), pre-diagnostic, PD (n=15), tumor, T (n=15), and adjacent normal, AN (n=15)) donated to the Susan G. Komen and Indiana University Simon Cancer Center Tissue Banks. These same samples were previously analyzed for microbiome composition and function using 16S rRNA sequencing (published in mSystems, 2022). Following sequence pre-processing, variant calling, and alternate allele frequency calculation by the UC Davis Bioinformatics Core, we selected only high and moderate variants for these genes with a quality score ≥ 55 for further analysis. Of the ten we intended to analyze, only 8 met these criteria within our data set: BRCA1, BRCA2, PTEN, TP53, PALB2, CHEK2, ATM , and BRIP1 . We ran generalized linear models to select variants with differences in alternate allele frequency among the tissue types (H, PD, AN, T, p ≤ 0.2). Alternate allele frequencies and genotypes of these variants that passed this filter were then associated with bacterial ASVs deemed differentially abundant relative to the H tissue type (mSystems, 2022) using MaAsLin2. Three BC-linked genes BRCA1, TP53 , and ATM show significant associations with the taxa, Muribaculaceae, Alcaligenes faecalis, Oceanobacillus, Romboutsia, Pseudomonas , and Pseudomonas fragi , at a p-value ≤ 0.01 and q-value ≤ 0.25. These genera belong to phyla (Bacteroides, Firmicutes, and Actinobacteria) which have been shown to either interact directly with the genome to produce cancer-causing DNA damage, or to be associated with other types of cancer, suggesting their likely role in tumorigenesis. The discovered associations further our understanding of the genetic and microbial determinants of breast cancer and may highlight the breast tissue bacteriome as a biomarker of BC. Citation Format: Ariana McCaw, Rachel Jiang, Lindsey Marian, Leah Stiemsma. The breast cancer genome and its association with the breast tissue bacteriome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A016.

Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms

To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential (CHIP) related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events (CCEs) in patients with myeloproliferative neoplasms (MPNs). The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed. Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients. Fifty-five cases of MPN (75.3%) showed positive in CHIP-related genes. There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia (ET) and polycythemia vera (PV). CHIP-related gene mutations were mainly single gene mutations, with mutation rate from high to low as JAK2V617F (63.0%, 46/73), ASXL1 (16.4%, 12/73), TET2 (11.0%, 8/73), DNMT3A (9.6%, 7/73), SRSF2 (6.9%, 5/73), SF3B1 (4.1%, 3/73), TP53(1.4%, 1/73) and PPM1D (1.4%, 1/73). The mutation rate of CHIP-related genes in MPN patients >60 years old was significantly higher than that in the patients ≤60 years old ［91.7%(33/36) vs 59.5%(22/37)］. CCEs occurred in 27 MPNs patients (37.0%, MPNs/CCEs), and 5 had recurrent CCEs, all of which were arterial events. Age (62.8±12.8 years vs 53.9±15.8 years, P =0.015), IL-1β level (17.7±26.0 vs 4.3±8.6, P =0.012), IL-8 level (360.7±598.6 vs 108.3±317.0, P =0.045), the proportion of the patients with thrombosis history (29.6% vs 2.2%, P =0.020), and the detection rate of CHIP-related mutations (88.9% vs 67.4%, P =0.040) in the group with CCEs were higher than those in the group without CCEs. Multivariate Logistic regression analysis showed that age（OR =0.917， 95%CI ：0.843-0.999, P =0.047）, thrombosis history (OR =34.148， 95%CI ：2.392-487.535, P =0.009), any CHIP-related mutations(OR =16.065， 95%CI ：1.217-212.024， P =0.035), and elevated level of IL-1β (OR =0.929， 95%CI ：0.870-0.992， P =0.027) were independent risk factors for MPNs/CCEs. CHIP-related gene mutations were not associated with CCEs in MPN patients, but DNMT3A (OR =88.717， 95%CI ：2.690-292.482， P =0.012) and ASXL1 (OR =7.941， 95%CI ：1.045-60.353， P =0.045) were independent risk factors for CCEs in PV. There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1β elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 β elevated levels may be the novel risk factors for CCEs in MPN.

Mass-Rearing Conditions Do Not Always Reduce Genetic Diversity: The Case of the Mexican Fruit Fly, Anastrepha ludens (Diptera: Tephritidae).

The application of the sterile insect technique (SIT) requires the adaptation of insects to mass-rearing conditions. It is generally accepted that this adaptation may include a reduction in genetic diversity and an associated loss of desirable characteristics for the effective performance of sterile insects in the field. Here, we compare the genetic diversity of two mass-reared strains of the Mexican fruit fly, Anastrepha ludens, and a wild (WIL) population collected near Tapachula, Mexico, using seven DNA microsatellites as molecular genetic markers. The mass-reared strains were a bisexual laboratory strain (LAB) with approximately 130 generations under mass-rearing and a genetic sexing strain, Tapachula-7 (TA7), also under mass-rearing for 100 generations. Our results revealed an overall low level of genetic differentiation (approximately 15%) among the three strains, with the LAB and WIL populations being genetically most similar and TA7 most genetically differentiated. Although there were some differences in allele frequencies between strains, our results show that overall, the adaptation to mass-rearing conditions did not reduce genetic variability compared to the wild sample in terms of heterozygosity or allelic richness, nor did it appear to alter the level of inbreeding with respect to the wild populations. These results are contrary to the general idea that mass-rearing always results in a reduction in genetic diversity. Overall, our findings can contribute to a better understanding of the impact that adaptation to mass-rearing conditions may have on the genetic make-up of strains.

Allele frequencies and genotype distribution of three metformin transporter polymorphisms in Mexican population and their application in pharmacogenomics of type 2 diabetes.

Metformin is the first-line antidiabetic therapy for type 2 diabetes in Mexico, despite recent recommendations highlighting alternatives like GLP-1 receptor agonists for individuals with obesity. Metformin elimination is reliant on liver and kidney function, and variants in transport proteins such as Multidrug and Toxin Extrusion Protein 1 (MATE1), MATE2, and Organic Cation Transporter 2 (OCT2) can influence its pharmacokinetics. Understanding these variants' frequencies in the Mexican population is crucial for tailoring personalized treatment strategies. This study aimed to determine the genotypic and allelic frequencies of key variants in metformin transporters within a Mexican population, addressing the interindividual variability in drug response. Genetic analysis was conducted on 101 healthy, unrelated Mexican subjects who were genotyped for the MATE1, MATE2, and OCT2 variants using allele-specific real-time PCR assays. The allele frequencies were 0.07 for OCT2, 0.23 for MATE1, and 0.67 for MATE2. The g.-66T→C variant was found only in wild-type and heterozygous forms. Comparative analysis indicated significant differences in allele frequencies between this Mexican population and other ethnic groups, highlighting potential implications for metformin efficacy and safety. This study provides crucial insights into the genetic variability of metformin transporter genes in a Mexican population, offering a foundation for personalized therapeutic approaches in type 2 diabetes management.

Association of polymorphism (RS1800896) of IL-10 gene and IL-10 gene expression in ovarian cancer patients from Georgia

Background/Aim: Ovarian cancer is one of the most important causes of tumour-associated mortality and morbidity in women. Some genetic alterations, determining predisposition to ovarian cancer have already been identified, but these are mostly syndrome-associated cases, most ovarian tumours are still regarded as sporadic. The aim of this research was to identify new predisposing factors that might increase ovarian cancer risk. Genetic variants of IL-10 gene in patients with ovarian cancer was analysed. Methods: Forty-eight patients with ovarian cancer along with 48 agematched controls were included in the study. Single nucleotide polymorphism (SNP) genotyping and gene expression assays for IL-10 were performed using TaqMan assay (Thermo Scientific, USA). The selected SNP was rs1800896 upstream of IL-10 gene (IL-10-1082). All statistical analyses were performed by GraphPad Prism 9.3.1 for Mac. Results: The genotype distributions of IL-10 gene polymorphisms among cancer and control groups were all according to the expected Hardy-Weinberg equilibrium. There was no statistically significant difference in frequency of genotypes and alleles between the two study groups (p > 0.05). In another analysis, the samples were grouped according to the polymorphic variant IL-10 (-1082) A/G. Subjects having the homozygous variant (A/A) had lower IL-10 mRNA levels than those with the homozygous wild (G/G) genotype in both, ovarian cancer patients and controls, p < 0.05. mRNA levels on IL-10 were different among cases and controls (p < 0.05). Patients with ovarian cancer had higher level of mRNA for IL-10. Conclusions: These results support the theory that IL-10 gene expression levels differ in patients with and without ovarian cancer. Polymorphic variant IL-10 (-1082) A/G couldn't be confirmed to explain this difference in gene expression levels.

Association of iron homeostasis-related gene polymorphisms with pregnancy and neonatal outcomes in patients with gestational diabetes mellitus.

The purpose of this study was to assess associations between iron homeostasis-related gene polymorphisms and gestational diabetes mellitus (GDM), adverse pregnancy outcomes, and neonatal outcomes. In total, 138 patients with GDM and 74 normal pregnancy controls were recruited. Time-of-flight mass spectrometry was used to genotype single-nucleotide polymorphisms (H63D rs1799945, TMPRSS6 rs855791, GDF15 rs1059369, rs4808793, BMP2 rs173107, C282Y rs3811647, rs1800562, rs269853, TF rs8177240, TFR2 rs7385804, FADS2 rs174577, and CUBN rs10904850) in 12 candidate genes related to iron homeostasis. Adverse pregnancy outcomes and neonatal health data were collected. Differences in genotype distributions and allele frequencies between patients and controls as well as their correlations with clinical factors were assessed. Additionally, associations between genotype, haemoglobin levels, and ferritin levels were evaluated. Pregnant women carrying the GDF15 rs4808793 allele (C) or TMPRSS6 rs855791 homozygous mutation (GG) had a significantly higher risk of GDM than that in the control group (p < 0.05). In patients with GDM, the BMP2 rs173107 heterozygous mutation (AC) was associated with significantly higher haemoglobin levels in late pregnancy compared with those for wild-type (AA) BMP2 (p < 0.05). Furthermore, in patients with GDM, the FADS2 rs174577 heterozygous mutation (AC) was associated with a significantly reduced risk of preterm birth (p < 0.05), the H63D rs1799945 heterozygous mutation (CG) was associated with a significantly increased risk of adverse neonatal outcomes (p < 0.05), TFR2 rs7385804 was associated a significantly reduced probability of caesarean section (p < 0.05), and the G mutation in TMPRSS6 rs855791 was related to a significantly increased probability of caesarean section (p < 0.05). These results suggest that polymorphisms in genes related to iron metabolism could potentially impact pregnancy and neonatal outcomes in patients with GDM. Large-scale studies are needed to further clarify the relationship between these polymorphisms and susceptibility to GDM.

Genetic insights into endurance athlete status: A meta-analysis of ACVR1B, AGT, FTO, IL-6, and NRF2 gene polymorphisms.

The aim of this meta-analysis was to analyze allele and genotype pattern frequencies of five different gene polymorphisms associated with endurance athlete status. Endurance sports require prolonged physical performance, and it is well known that physiological and genetic characteristics play a prominent role in this performance. In recent years, research on the impact of genetic factors on endurance athlete status has been on the rise, suggesting that various gene polymorphisms may be associated with physical performance. Specifically, the gene polymorphisms, activin receptor type-1B (A9CVR1B) rs2854464, angiotensinogen (AGT) rs699, fat mass and obesity-associated (FTO) rs9939609, interleukin-6 (IL-6) rs1800795, and nuclear factor erythroid 2 (NRF2) rs12594956, are thought to be related to endurance athlete status. Each of these genes plays a part in different biological processes, such as muscle development, energy metabolism, inflammation, and antioxidant defense mechanisms. For example, the NRF2 gene is a critical player in the regulation of cellular stress responses and may contribute to adaptive responses that enhance performance in endurance athletes. This meta-analysis included a total of 20 articles published between 2009 and 2023. The specific gene polymorphisms explored in this study, i.e., ACVR1B rs2854464, AGT rs699, FTO rs9939609, IL-6 rs1800795, and NRF2 rs12594956, were selected due to their reported associations with physical performance and endurance. A comprehensive search was conducted in the Web of Science and PubMed databases using specific keywords, preliminarily identifying 329 articles. Upon analysis of the abstracts, and full texts, 20 articles were deemed eligible for inclusion in this meta-analysis. Articles lacking control and endurance athlete groups or clear allele/genotype data were excluded. The findings indicated no significant differences in allele and genotype frequencies for ACVR1B, AGT, FTO, and IL-6 gene polymorphisms between endurance athletes and control groups. However, the NRF2 rs12594956 gene polymorphism showed a significantly higher frequency of the major allele (A) and the AA genotype in endurance athletes than in controls. In conclusion, the NRF2 rs12594956 polymorphism may be a genetic variant of interest in determining the status of endurance athletes. These findings highlight the potential clinical implications for genetic screening and personalized training programs in sport genetics. More extensive studies with larger cohorts are needed to further confirm these associations.

Identification of Breed-Specific SNPs in Ethiopian Indigenous and European Beef Cattle Breeds and how they May Influence Adaptation and Selection Signatures

Background: Understanding the genetic foundation of locally adapted indigenous cattle breeds is critical information for developing appropriate genetic improvement and conservation initiatives. To investigate breed-specific SNPs, and minor allele frequency of three Ethiopian cattle breeds Begait, (n = 40), Boran (n = 40), and Fogera (n = 43) were genotyped with 80K SNP array. Three European beef cattle breeds (Angus, n = 42), Hereford (n = 35), and Charolais (n = 37) were also used for comparison. Results: The average minor allele frequency was 0.19 ± 0.17, 0.20 ± 0.17, 0.21± 0.17, 0.31 ± 0.13, 0.32 ± 0.12, 0.32 ± 0.13 for Angus, Herford, Charolais, Boran, Fogera, and Begait cattle, respectively. Minor allele frequency difference was observed between Ethiopian indigenous and European beef cattle breeds. Across the Ethiopian and European cattle breeds, a common variant minor allele frequency (≥0.10 and ≤ 0.5) accounted 94% and 62%, respectively. A total of 7759 and 48 SNPs were identified as breed-specific in Ethiopian cattle breeds and European beef cattle breeds respectively. These SNPs resided with 3364 genes for Ethiopian cattle breeds and 17 genes for European beef cattle breeds. Interestingly important biological processes and pathways related to tropical adaptation in Ethiopian cattle populations were identified through gene Ontology analysis. Conclusions: The higher minor allele frequency and breed-specific SNPs detected in Ethiopian indigenous breeds show the presence of high genetic variability. This genetic variation in Ethiopian cattle breeds is used as a potential source for future breeding programs.

Russian Regional Differences in Allele Frequencies of CFTR Gene Variants: Genetic Monitoring of Infertile Couples.

A male factor, commonly associated with poor semen quality, is revealed in about 50% of infertile couples. CFTR gene (Cystic Fibrosis Transmembrane Conduction Regulator) variants are one of the common genetic causes of azoospermia-related male infertility. Notably, the spectrum and frequency of pathogenic CFTR variants vary between populations and geographical regions. In this work, we made an attempt to evaluate the allele frequency (AF) of 12 common CFTR variants in infertile Russian men and healthy individuals from different districts of Russia. Because of the limited number of population-based studies on Russian individuals, we characterized the population AFs based on data from the Registry of Russian cystic fibrosis (CF) patients. In addition to the CF patient registry, we estimated the local frequencies of the same set of variants based on the results of genotyping of CF patients in local biocollections (from St. Petersburg and Yugra regions). AFs of common CFTR variants calculated based on registry and biocollection data showed good concordance with directly measured population AFs. The estimated region-specific frequencies of CFTR variants allowed us to uncover statistically significant regional differences in the frequencies of the F508del (c.1521_1523del; p.Phe508del) and CFTRdele2,3(21kb) (c.54-5940_273+10250del21kb; p.Ser18ArgfsX) variants. The data from population-based studies confirmed previous observations that F508del, CFTRdele2,3(21kb), and L138ins (c.413_415dup; p.Leu138dup)variants are the most abundant among infertile patients, and their frequencies are significantly lower in healthy individuals and should be taken into account during genetic monitoring of the reproductive health of Russian individuals.

Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children

ABSTRACT Objective To investigate the association between loci rs3761847 and rs10818488 of tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) gene and the susceptibility to IgAV. Methods 100 blood samples of children with IgAV and 100 blood samples of healthy children were collected from the Third Xiangya Hospital of Central South University from June 2017 to June 2019. The target gene fragment was amplified by polymerase chain reaction (PCR), and the single nucleic acid gene polymorphism of the gene loci was detected by PCR sequencing based typing technique. The association between gene polymorphism of each locus and susceptibility to IgAV was analyzed. Results There were significant differences in both genotype (P < .05) and allele frequencies （P < .05) of rs3761847 of TRAF1/C5 gene between the IgAV group and the control group.Besides, the risks of developing IgAV in children with the TT genotype was 0.495 times and in children with the C allele was 1.627 times of that in children with other genotypes and alleles, respectively (P < .05). For IgAV patients, renal involvement risk in children with CC genotype was 5.859 times of that in children with other genotypes (P < .05). There were no significant differences in genotype (P > .05) and allele frequencies (P > .05) of rs10818488 of TRAF1/C5 gene between the IgAV group and the control group. IgAV patients with TT genotype had a 3.2 times higher risk of renal involvement than those with other genotypes (P < .05). Conclusions There is an association between locus rs3761847 of TRAF1/C5 gene single nucleotide polymorphisms and susceptibility to IgAV. The T allele at locus rs3761847 of TRAF1/C5 gene may be a protective factor for IgAV. The C allele at locus rs3761847 and the T allele at locus rs10818488 of TRAF1/C5 gene may be associated with kidney injury in IgAV.

Underrepresentation of Diverse Ancestries Drives Uncertainty in Genetic Variants Found in Cardiomyopathy-Associated Genes

BackgroundThousands of genetic variants have been identified in cardiomyopathy-associated genes. Diagnostic genetic testing is key for evaluation of individuals with suspected cardiomyopathy. While accurate variant pathogenicity assignment is important for diagnosis, the frequency of and factors associated with clinically relevant assessment changes are unclear. ObjectivesThe authors aimed to characterize pathogenicity assignment change in cardiomyopathy-associated genes and to identify factors associated with this change. MethodsWe identified 10 sarcomeric and 6 desmosomal genetic cardiomyopathy-associated genes along with comparison gene sets. We analyzed clinically meaningful changes in pathogenicity assignment between any of the following: pathogenic/likely pathogenic (P/LP), conflicting interpretations of pathogenicity or variant of unknown significance (C/VUS), and benign/likely benign. We explored association of minor allele frequency (MAF) differences between well, and traditionally poorly, represented ancestries in genetic studies with assessment stability. Analyses were performed using ClinVar and GnomAD data. ResultsOf the 30,975 cardiomyopathy-associated gene variants in ClinVar, 2,276 of them (7.3%) had a clinically meaningful change in pathogenicity assignment over the study period, 2011 to 2021. Sixty-seven percent of variants that underwent a clinically significant change moved from P/LP or benign/likely benign to C/VUS. Among cardiomyopathy variants downgraded from P/LP, 35% had a MAF above 1 × 10−4 in non-Europeans and below 1 × 10−4 in Europeans. ConclusionsOver the past 10 years, 7.3% of cardiomyopathy gene variants underwent a clinically meaningful change in pathogenicity assignment. Over 30% of downgrades from P/LP may be attributable to higher MAF in Non-Europeans than Europeans. This finding suggests that low ancestral diversity in genetic studies has increased diagnostic uncertainty in cardiomyopathy gene variants.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis

BackgroundLong non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility.MethodsA total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls.ResultsNo significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant–recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls.ConclusionsOur study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

Comprehensive whole-genome analyses of the UK Biobank reveal significant sex differences in both genotype missingness and allele frequency on the X chromosome.

The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has identified autosomal SNPs with significant sdMAF, including in the UK Biobank, but the X chromosome was excluded. Our recent report identified multiple regions on the X chromosome with significant sdMAF, using short-read sequencing of other datasets. We performed a whole genome sdMAF analysis, with ~410k white British individuals from the UK Biobank, using array genotyped, imputed or exome sequencing data. We observed marked sdMAF on the X chromosome, particularly at the boundaries between the pseudo-autosomal regions (PAR) and the non-PAR (NPR), as well as throughout the NPR, consistent with our earlier report. A small fraction of autosomal SNPs also showed significant sdMAF. Using the centrally imputed data, which relied mostly on low-coverage whole genome sequence, resulted in 2.1% of NPR SNPs with significant sdMAF. The whole exome sequencing also displays sdMAF on the X chromosome, including some NPR SNPs with heterozygous genotype calls in males. Genotyping, sequencing and imputation of X chromosomal SNPs requires further attention to ensure the integrity for downstream association analysis.

Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option

BackgroundPreeclampsia is the main cause of preterm parturition and maternal–fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels.ObjectiveThis study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia.MethodsIn this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out.ResultsOur statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin‐13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant.ConclusionsNo risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.