Individual Genotypes Research Articles

Genetic Association of ICAM-1 (rs5498) Gene Polymorphism With Susceptibility to Stage II Grade B Periodontitis: A Case-Control Study in South Indian Population.

In the contemporary perspective, periodontitis is considered a complex issue triggered and perpetuated by bacteriabut strongly influenced by the way the body reacts to bacterial plaque. Recent research has indicated that variations in genes might have an impact on the development of periodontitis. This study was conducted to explore a probable link between the genetic variations in intercellular adhesion molecule-1 (ICAM-1) represented by rs5498 and the occurrence of periodontitis. Methods: A total of 100 participants, 50 with periodontitis and 50 with periodontally healthy or mild gingivitis, were recruited for this study. Whole blood drawn from the participants was used to obtain genomic DNA. The ICAM-1 gene polymorphism (rs5498) was determined using polymerase chain reaction (PCR) amplification and digestion. The ICAM-1 gene's flanking primers were used to amp up the DNA. For statistical analysis, the genotype that was analyzed using the pattern of restriction fragment length polymorphism was recorded. The Chi-square test compared genotype and allele frequency distributions between both groups. The odds ratio with 95% confidence intervals with each individual allele or genotype was used to compute the risk. Statistical significance was established in all tests when the p-value was less than 0.05. There was no discernible difference between the genotype frequencies of patients and controls χ2df (P = 0.6065). The findings demonstrated that no significant difference was present between the two groups for homozygous or heterozygous mutant genotypes (AA vs. AG+GG; P = 0.6854). There was no discernible difference in the detected frequencies of the A allele (58% vs. 61%), G allele (42% vs. 39%), TT (16% vs. 24%), AG (40% vs. 36%), and TT genotypes in the studied groups. According to the results of the current investigation, the ICAM-1 (rs5498) gene polymorphism is not associated with periodontitis in the population investigated.

Association of MTHFD1 G1958A, MTHFD1 T401C and CBS 844ins68bp with Breast Cancer in Jordan

MTHFD1 and CBS genes have key roles in folate and homocysteine metabolism. Many studies reported an association between cancer pathogenesis and different functional SNPs of genes involved in the main folate metabolism and the transsulfuration pathway. The current population-based, case-control study examined the association between MTHFD1 G1958A, MTHFD1 T401C, and the CBS 844ins68 insertion with breast cancer (BC) risk in Jordanian women. The studied population included 200 female BC subjects and age-matched female controls. The targeted genotypes MTHFD1 G1958A and MTHFD1 T401C were amplified via PCR followed by subsequent digestion with the proper restriction enzyme (PCR-RFLP), while the insertion/deletion of CBS844ins68bp was visualized and scored directly after gel electrophoresis. Results showed that the examined individual alleles and genotypes of MTHFD 1958A, MTHFD1 401C, and CBS844ins68bp per se were not associated with risk of BC compared with their wild-type genotypes and alleles.

No evidence for a role of MHC class II genotype in the chemical encoding of heterozygosity and relatedness in Antarctic fur seals.

Despite decades of research, surprisingly little is known about the mechanism(s) by which an individual's genotype is encoded in odour. Many studies have focused on the role of the major histocompatibility complex (MHC) owing to its importance for survival and mate choice. However, the salience of MHC-mediated odours compared to chemicals influenced by the rest of the genome remains unclear, especially in wild populations where it is challenging to quantify and control for the effects of the genomic background. We addressed this issue in Antarctic fur seals by analysing skin swabs together with full-length MHC DQB II exon 2 sequences and data from 41 genome-wide distributed microsatellites. We did not find any effects of MHC relatedness on chemical similarity and there was also no relationship between MHC heterozygosity and chemical diversity. However, multilocus heterozygosity showed a significant positive association with chemical diversity, even after controlling for MHC heterozygosity. Our results appear to rule out a dominant role of the MHC in the chemical encoding of genetic information in a wild vertebrate population and highlight the need for genome-wide approaches to elucidate the mechanism(s) and specific genes underlying genotype-odour associations.

Multiple high-risk HPV infections probably associated with a higher risk of low-grade cytological abnormalities but not with high-grade intraepithelial lesions of the cervix

BackgroundFor women diagnosed with HR-HPV DNA positivity in community hospitals, the necessity of investigating the potential presence of multiple HR-HPV infections upon referral to tertiary medical institutions remains unclear.MethodsIn our cohort, women tested positive for HR-HPV DNA during examinations in community hospitals, were subsequently referred to tertiary medical facilities, reevaluated HR-HPV genotype and categorized based on cytological and histopathological results. The risk of cytologic/histopathology abnormalities and ≧ high grade squamous intraepithelial lesion(HSIL) or Cervical Intraepithelial Neoplasia (CIN) 2 associated with individual genotypes and related multiple HPV infections are calculated.ResultsA total of 1677 women aged between 21 and 77 were finally included in the present study. The cytology group included 1202 women and the histopathological group included 475 women with at least one HR-HPV infection of any genotype. We only observed a higher risk of low grade cytological abnormalities in women with multiple infections than those in corresponding single infections (for all population with an OR of 1.85[1.39–2.46]; p < 0.05). However, this phenomenon was not observed in histopathology abnormalities (CIN1). The risk of developing of ≥ HSIL/CIN2 in women who were infected with multiple HR-HPV also showed a similar profile to those with a single HR-HPV genotype.ConclusionMultiple HR-HPV infections is only associated with a higher associated risk of low grade cytological abnormalities. There is no evidence of clinical benefit to identify the possible presence of multiple HR-HPV infection frequently in a short period of time for women with HR-HPV-DNA positive.

The BDNF protein is associated with glucose homeostasis and food intake in carriers of common BDNF gene variants.

The brain-derived neurotrophic factor (BDNF) concentrations may differ between BDNF gene genotype carriers. These changes occur in individuals with metabolic and mental disorders. The aim of this study was to assess the associations of glucose homeostasis parameters and the frequency of food consumption with BDNF protein concentrations based on the BDNF single-nucleotide polymorphisms (SNPs). Among the 439 participants, some common rs10835211 BDNF gene variants were analyzed. We evaluated BDNF concentration, fasting glucose and insulin concentrations and during oral glucose tolerance tests. Anthropometric measurements, body composition, and body fat distribution were assessed, and 3-day food intake diary and food frequency questionnaire were completed. We noticed significant differences in concentration of BDNF between AA and AG genotype rs10835211 carriers (p=0.018). The group of AA genotype holders were older, and positive correlation was found between age and BDNF in the whole study population (p=0.012) and in the GG genotype carriers (p=0.023). Moreover, BDNF protein correlated with fasting insulin (p=0.015), HOMA-IR (p=0.031), HOMA-B (p=0.010) , and the VAT/SAT ratio (p=0.026) in the GG genotype individuals. Presence of the GG genotype was negatively correlated with nut and seed (p=0.047), lean pork consumption (p=0.015) and the BDNF protein. Moreover, we observed correlations between the frequency of chicken (p=0.028), pasta (p=0.033) and sweet food intake (p=0.040) and BDNF concentration in the general population. Among carriers of the AA genotype, we observed a positive correlation between the consumption of rice (p=0.048) and sweet food (p=0.028) and the BDNF protein level. Peripheral BDNF may be associated with visceral fat content and insulin concentrations in the GG genotype carriers and may depend on variable food intake, which warrants further investigation.

An integrative approach to assessing the pathogenic potential of &lt;i&gt;Escherichia coli&lt;/i&gt; strains isolated from urine

Introduction. Uropathogenic Escherichia coli (UPEC) are characterized by the ability to survive and reproduce in the urinary tract due to the presence of specific virulence factors. In routine laboratory practice, the detection of diagnostically significant bacteriuria does not provide an idea of the level of infection of the urinary system (renal parenchyma, bladder), the pathogenic potential of the strain in the progression and chronicity of the infectious process, and the occurrence of life-threatening conditions (urosepsis, meningitis).&#x0D; Objective. To characterize the population structure, genetic diversity and pathogenic potential of E. coli strains isolated from urine.&#x0D; Materials and methods. 194 strains of E. coli isolated from urine were studied. Detection of 17 genes encoding the synthesis of: adhesins (pap, fimH, sfa, focG, afa), toxins (hlyA, cvaC, cnf, cdtB), capsular antigens (kpsMTII, kpsMTIII, kpsMT K1), siderophores (fyuA, iutA), invasins (ibeA), genetic markers of the pathogenicity island (PAI) of UPEC CFT073, the gene (traT) encoding serum resistance capacity and phylogenetic groups were performed by PCR (CXT-1000, BioRad, USA) with published primers (Synthol, Sibenzyme, Evrogen, Russia). To assess the statistical significance of differences, Fisher's exact test was used. Differences were considered significant at a confidence interval of 95% (p 0.05).&#x0D; Results. E. coli strains more often (p 0.05) belonged to the phylogenetic group B2 (57.7%). Pathogenetically significant virulence determinants were identified in 97.9% of strains. Based on the combination of 17 genes, 134 individual virulence genotypes were identified. In 93.3% of strains, a genetic predisposition to the occurrence of recurrent urinary tract infections (UTIs) was revealed, in 6.9% there was a potential for the development of pyelonephritis and recurrent cystitis. Markers of life-threatening complications of UTI were identified in 12% of strains, of which 10.7% were the development of urosepsis and 1.3% were meningitis.&#x0D; Conclusion. Detection of a complex of genes in E. coli strains isolated from urine confirms the etiological significance of the isolate and allows one to assess the pathogenic potential for the development of chronic and severe life-threatening complications.

EpiVar Browser: advanced exploration of epigenomics data under controlled access.

Human epigenomic data has been generated by large consortia for thousands of cell types to be used as a reference map of normal and disease chromatin states. Since epigenetic data contains potentially identifiable information, similarly to genetic data, most raw files generated by these consortia are stored in controlled-access databases. It is important to protect identifiable information, but this should not hinder secure sharing of these valuable datasets. Guided by the Framework for responsible sharing of genomic and health-related data from the Global Alliance for Genomics and Health (GA4GH), we have developed an approach and a tool to facilitate the exploration of epigenomics datasets' aggregate results, while filtering out identifiable information. Specifically, the EpiVar Browser allows a user to navigate an epigenetic dataset from a cohort of individuals and enables direct exploration of genotype-chromatin phenotype relationships. Because individual genotypes and epigenetic signal tracks are not directly accessible, and rather aggregated in the portal output, no identifiable data is released, yet the interface allows for dynamic genotype-epigenome interrogation. This approach has the potential to accelerate analyses that would otherwise require a lengthy multi-step approval process and provides a generalizable strategy to facilitate responsible access to sensitive epigenomics data. Online portal: https://computationalgenomics.ca/tools/epivar; EpiVar Browser source code: https://github.com/c3g/epivar-browser; bw-merge-window tool source code: https://github.com/c3g/bw-merge-window.

Association of PADI2 and PADI4 polymorphisms in COVID-19 host severity and non-survival

BackgroundEnzymes of the peptidylarginine deiminase family (PADs) play a relevant role in the pathogenesis of COVID-19. However, the association of single nucleotide polymorphisms (SNPs) in their genes with COVID-19 severity and death is unknown. MethodologyWe included 1045 patients who were diagnosed with COVID-19 between October 2020 and December 2021. All subjects were genotyped for PADI2 (rs1005753 and rs2235926) and PADI4 (rs11203366, rs11203367, and rs874881) SNPs by TaqMan assays and their associations with disease severity, death, and inflammatory biomarkers were evaluated. Results291 patients presented had severe COVID-19 according to PaO2/FiO2, and 393 had a non-survival outcome. Carriers of the rs1005753 G/G genotype in the PADI2 gene presented susceptibility for severe COVID-19, while the heterozygous carriers in rs11203366, rs11203367, and rs874881 of the PADI4 gene showed risk of death. The GTACC haplotype in PADI2-PADI4 was associated with susceptibility to severe COVID-19, while the GCACC haplotype was a protective factor. The GCGTG haplotype was associated with severe COVID-19 but as a protective haplotype for death. Finally, the GTACC haplotype was associated with platelet-to-lymphocyte ratio (PLR), the GCACC haplotype with neutrophil-to-hemoglobin and lymphocyte and the GCGTG haplotype as a protective factor for the elevation of procalcitonin, D-dimer, CRP, LCRP, NHL, SII, NLR, and PLR. ConclusionsOur results suggest that the haplotypic combination of GTACC and some individual genotypes of PADI2 and PADI4 contribute to the subjects' susceptibility for severity and death by COVID-19.

Correlation of the HPV 16 Genotype Persistence in Women Undergoing LEEP for CIN3 with the Risk of CIN2+ Relapses in the First 18 Months of Follow-Up: A Multicenter Retrospective Study.

Specific hr-HPV genotypes have different natural histories and different oncogenic capacity. This study aimed to investigate the risk of CIN2+ recurrence of the individual genotypes and evaluate how the duration of HPV persistence influences the risk of developing recurrent 16 cervical dysplasia of high grade (CIN2+). Data from patients with persistent HPV infection after primary conization were retrospectively extracted. Kaplan-Meier proportional hazards models were used to evaluate associations between the duration of HPV persistence and the risk of developing recurrent CIN2+. Kruskal-Wallis testing with Dunn's multiple comparison test was used to test whether there was a statistically significant difference in the time to development of tumor recurrences between different genotypes. Overall, 333 patients met the inclusion criteria. In 285 cases the HPV infection was persistent, in 48 cases (18%) it was transient, i.e., different genotypes after LEEP. Overall were diagnosed 39 relapses (13.7%), 79.5% (31/39 cases) were due to genotype 16, 20.5% (8/39) were linked to the other genotypes. Persistence of genotype 16 showed a 7-fold increased risk of developing a CIN2+ relapse, OR = 7.08 (95%CI: 3.12-16.08). Furthermore, the majority of relapses (38/39) occurred within 24 months of persistence with a cut-off represented by 18 months (p = 0.001) in which the relapse rate is maximum and the most frequently found genotype was the 16th with 31 (79.5%) cases of recurrence. Kruskal-Wallis test with Dunn's multiple comparisons has shown statistically significant difference in the time of development of CIN2 relapses among HPV16 and other genotypes. (p < 0.05). Kaplan-meier analysis has shown statistically significant difference between the time to CIN2+ relapse onset in patients with HPV 16 infection and patients with other hrHPV genotypes. (p < 0.05) Conclusions: the study results suggest that persistent HPV infection after LEEP with the same HR genotype present before surgery represents one of the most important predictive factors of the risk of CIN2+ recurrence. The persistence of HPV16 for the first 18 months strongly correlates with the risk of developing a CIN2+ recurrence.

The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3.

A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone.

Simulating pollen flow and field sampling constraints helps revise seed sampling recommendations for conserving genetic diversity.

In this study, we use simulations to determine how pollen flow and sampling constraints can influence the genetic conservation found in seed collections. We simulated genotypes of parental individuals and crossed the parentals based on three different ranges of pollen flow (panmictic, limited, and highly limited) to create new seed sets for sampling. We tested a variety of sampling scenarios modeled on those occurring in nature and calculated the proportion of alleles conserved in each scenario. We found that pollen flow greatly influences collection outcomes, with panmictic pollen flow resulting in seed sets containing 21.6% more alleles than limited pollen flow and 48.6% more alleles than highly limited pollen flow, although this impact diminishes when large numbers of maternal plants are sampled. Simulations of realistic seed sampling (sampling more seed from some plants and fewer from others) showed a relatively minor impact (<2.5%) on genetic diversity conserved compared to ideal sampling (uniform sampling across all maternal plants). We conclude that future work must consider limited pollen flow, but collectors can be flexible with their sampling in the field as long as many unique maternal plants are sampled. Simulations remain a fruitful method to advance ex situ sampling guidelines.

Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders

APOL1 variants G1 and G2 are common in populations with recent African ancestry. They are associated with protection from African sleeping sickness, however homozygosity or compound heterozygosity for these variants is associated with chronic kidney disease (CKD) and related conditions. What is not clear is the extent of associations with non-kidney-related disorders, and whether there are clusters of diseases associated with individual APOL1 genotypes. Using a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes. We identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were specifically associated with 26 of these conditions (all deleteriously), with an over-representation of infectious diseases (including hospitalisation and death resulting from COVID-19). The analysis also exposed complexities in the relationship between APOL1 and CKD that are not evident when risk variants are grouped together: G1 homozygosity, G2 homozygosity, and G1/G2 compound heterozygosity were each shown to be associated with distinct CKD phenotypes. The multi-locus nature of the G1/G2 genotype means that its associations would go undetected in a standard genome-wide association study. Our findings have implications for understanding health risks and better-targeted detection, intervention, and therapeutic strategies, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora. This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).

PEPS: Polygenic Epistatic Phenotype Simulation.

Genetic data is limited and generating new datasets is often an expensive, time-consuming process, involving countless moving parts to genotype and phenotype individuals. While sharing data is beneficial for quality control and software development, privacy and security are of utmost importance. Generating synthetic data is a practical solution to mitigate the cost, time and sensitivities that hamper developers and researchers in producing and validating novel biotechnological solutions to data intensive problems. Existing methods focus on mutation frequencies at specific loci while ignoring epistatic interactions. Alternatively, programs that do consider epistasis are limited to two-way interactions or apply genomic constraints that make synthetic data generation arduous or computationally intensive. To solve this, we developed Polygenic Epistatic Phenotype Simulator (PEPS). Our tool is a probabilistic model that can generate synthetic phenotypes with a controllable level of complexity.

ACE I/D polymorphism is a risk factor for the clinical severity of COVID-19 in Brazilian male patients.

The renin-angiotensin system is potentially involved in the pathogen-host interaction in the disease caused by SARS-CoV-2, since the angiotensin-converting enzyme (ACE) 2 serves as a receptor for the virus. The impact of the pandemic in specific regions and ethnic groups highlights the importance of investigating genetic factors that disrupt the balance of the system in response to SARS-CoV-2 infection, especially in genes with ethnic frequency variations. Therefore, this study aimed to evaluate the influence of the ACE I/D polymorphism on the incidence and severity of COVID-19 in a sample of the Brazilian population. 70 severe cases and 355 mild cases patients were evaluated. DNA extraction was performed using a QIAamp DNA Blood Mini kit. Genotyping of ACE I/D polymorphism was performed. Clinical outcomes were obtained from the patients' records. We found an association between the ACE I/D polymorphism and the incidence or severity of COVID-19 in male participants. Moreover, we observed a relationship between severity and increasing age and body weight and a higher frequency of II genotype individuals among those who had a cough as their symptoms in mild patients. No differences were observed in leukocyte count or other parameters related to the inflammatory response in severe patients. Our data showed the influence of the ACE I/D polymorphism on severity of COVID-19 in males, as well as on the occurrence of cough in patients with mild symptoms, with a higher incidence in those carrying the I allele.

Exploring the influence of DNA methylation and single nucleotide polymorphisms of the Myostatin gene on growth traits in the hybrid grouper (Epinephelus fuscoguttatus (female) × Epinephelus polyphekadion (male)).

Investigations into the correlation between growth characteristics and DNA methylation levels, along with genetic variations, can provide fundamental insights to enhance growth performance in groupers. The Myostatin (mstn) gene plays a vital role in regulating skeletal muscle development and growth. This study scrutinized the DNA methylation levels of the mstn gene across hybrid groupers (E. fuscoguttatus (♀) × E. polyphekadion (♂)) and their parental species, to evaluate its impact on growth attributes in grouper fish. The nucleotide sequence of the mstn gene was directly sequenced in the hybrid grouper, exhibiting different growth performance to identify the single nucleotide polymorphisms (SNPs) of the mstn gene and explore their correlation with growth characteristics. The findings revealed no significant differences in global DNA methylation levels within muscle tissue among the hybrid grouper and parents. However, significant differences in DNA methylation sites were discovered between the hybrid grouper and E. polyphekadion at sites 824 and 1521 (located at exon 2 and intron 2, respectively), and between E. fuscoguttatus and E. polyphekadion at site 1521. These variations could potentially influence the mRNA expression of the mstn gene. The study also identified that SNP g.1003 T > C in exon 2 of the mstn gene was significantly associated with various growth traits including body weight, total length, body length, head length, caudal peduncle height, and body height (p < 0.01). Specimens with the TT genotype at site 1003 demonstrated superior growth performance compared to those with the TC genotype. Furthermore, microstructural analyses of muscle tissue showed that the average area and diameter of muscle fibers in TT genotype individuals were significantly greater than those in TC genotype individuals. Therefore, this research provides robust evidence linking the DNA methylation level and polymorphisms of the mstn gene with growth traits, which could be beneficial for grouper breeding programs.

PDE9A polymorphism and association analysis with growth performance and gastrointestinal weight of Hu sheep

Phosphodiesterase 9A (PDE9A) plays a crucial role in activating the cGMP-dependent signaling pathway and may have important effects on the growth and development of the gastrointestinal tract in Hu sheep. In this study, we analyzed the single nucleotide polymorphisms of PDE9A in 988 Hu sheep and their correlation with growth performance, feed efficiency, and gastrointestinal development. Additionally, we examined the expression level of different PDE9A genotypes in the gastrointestinal tract of Hu sheep by using fluorescence quantitative PCR. The results revealed a moderate level of polymorphism (0.25 < PIC < 0.50) at the g.286248617 T > C mutation site located in the first intron of PDE9A in Hu sheep, with three genotypes: CC, CT, and TT. The weights of the omasum, colon, and cecum were significantly greater in the CC genotype than in the TT genotype (P < 0.05), and the expression level of PDE9A in the tissues of the rumen, ileum, cecum, and colon was notably lower in the CC genotype individuals (P < 0.05). These findings suggest that the polymorphism of PDE9A affects the weight of the stomach, colon, and cecum in Hu sheep through expression regulation. Overall, the results of this study suggest that the g.286248617 T > C mutation site in the first intron of PDE9A can serve as a potential molecular marker for breeding practices related to the gastrointestinal weight of Hu sheep.

Dissecting the resilience of barley genotypes under multiple adverse environmental conditions

As climate change increases abiotic stresses like drought and heat, evaluating barley performance under such conditions is critical for maintaining productivity. To assess how barley performs under normal conditions, drought, and heat stress, 29 different varieties were examined, considering agronomic, physiological, and disease-related characteristics. The research was conducted in five environments: two normal environments in 2020/2021 and 2021/2022, two drought stress environments in 2020/2021 and 2021/2022, and one heat stress environment in 2021/2022. The results demonstrated that genotype and environment significantly influenced all traits (p < 0.05), except canopy temperature, while genotype x environment interaction significantly influenced most traits, except total chlorophyll content and canopy temperature. Heat and drought stress environments often resulted in reduced performance for traits like plant height, spike length, grains per spike, and 100-grain weight compared to normal conditions. Based on individual traits, genotypes 07UT-44, 06WA-77, 08AB-09, and 07N6-57 exhibited the highest grain yield (4.1, 3.6, 3.6, and 3.6 t/ha, respectively). Also, these genotypes demonstrated enhanced stability in diverse drought and heat stress conditions, as assessed by the mean performance vs. stability index (Weighted Average of Absolute Scores, WAASB). The multi-trait stability index (MTSI) identified 07UT-44, 07UT-55, 07UT-71, and 08AB-09 as the most stable genotypes in terms of the performance of all traits. The imported lines demonstrated superior performance and stability, highlighting their potential as valuable genetic resources for developing climate-resilient barley.

Exploring the costs of phenotypic plasticity for evolvable digital organisms

Phenotypic plasticity is usually defined as a property of individual genotypes to produce different phenotypes when exposed to different environmental conditions. While the benefits of plasticity for adaptation are well established, the costs associated with plasticity remain somewhat obscure. Understanding both why and how these costs arise could help us explain and predict the behavior of living creatures as well as allow the design of more adaptable robotic systems. One of the challenges of conducting such investigations concerns the difficulty of isolating the effects of different types of costs and the lack of control over environmental conditions. The present study addresses these challenges by using virtual worlds (software) to investigate the environmentally regulated phenotypic plasticity of digital organisms. The experimental setup guarantees that potential genetic costs of plasticity are isolated from other plasticity-related costs. Multiple populations of organisms endowed with and without phenotypic plasticity in either the body or the brain are evolved in simulation, and organisms must cope with different environmental conditions. The traits and fitness of the emergent organisms are compared, demonstrating cases in which plasticity is beneficial and cases in which it is neutral. The hypothesis put forward here is that the potential benefits of plasticity might be undermined by the genetic costs related to plasticity itself. The results suggest that this hypothesis is true, while further research is needed to guarantee that the observed effects unequivocally derive from genetic costs and not from some other (unforeseen) mechanism related to plasticity.

High prevalence of high-risk HPV genotypes in individuals attending an infectious diseases clinic from 2018 to 2022 in Milan, Italy.

Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR-HPV, 8 probable/possible HR-HPV, and 8 LR-HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high-risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR-HPV, LR-HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR-HPV, instead of LR-HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR-HPV coinfections, reinforces the urge to intensify the anti-HPV vaccination campaign.

Large changes in detected selection signatures after a selection limit in mice bred for voluntary wheel-running behavior.

In various organisms, sequencing of selectively bred lines at apparent selection limits has demonstrated that genetic variation can remain at many loci, implying that evolution at the genetic level may continue even if the population mean phenotype remains constant. We compared selection signatures at generations 22 and 61 of the "High Runner" mouse experiment, which includes 4 replicate lines bred for voluntary wheel-running behavior (HR) and 4 non-selected control (C) lines. Previously, we reported multiple regions of differentiation between the HR and C lines, based on whole-genome sequence data for 10 mice from each line at generation 61, which was >31 generations after selection limits had been reached in all HR lines. Here, we analyzed pooled sequencing data from ~20 mice for each of the 8 lines at generation 22, around when HR lines were reaching limits. Differentiation analyses of allele frequencies at ~4.4 million SNP loci used the regularized T-test and detected 258 differentiated regions with FDR = 0.01. Comparable analyses involving pooling generation 61 individual mouse genotypes into allele frequencies by line produced only 11 such regions, with almost no overlap among the largest and most statistically significant peaks between the two generations. These results implicate a sort of "genetic churn" that continues at loci relevant for running. Simulations indicate that loss of statistical power due to random genetic drift and sampling error are insufficient to explain the differences in selection signatures. The 13 differentiated regions at generation 22 with strict culling measures include 79 genes related to a wide variety of functions. Gene ontology identified pathways related to olfaction and vomeronasal pathways as being overrepresented, consistent with generation 61 analyses, despite those specific regions differing between generations. Genes Dspp and Rbm24 are also identified as potentially explaining known bone and skeletal muscle differences, respectively, between the linetypes.