Related Genotypes Research Articles

Efficient permutation-based genome-wide association studies for normal and skewed phenotypic distributions.

MotivationGenome-wide association studies (GWAS) are an integral tool for studying the architecture of complex genotype and phenotype relationships. Linear mixed models (LMMs) are commonly used to detect associations between genetic markers and a trait of interest, while at the same time allowing to account for population structure and cryptic relatedness. Assumptions of LMMs include a normal distribution of the residuals and that the genetic markers are independent and identically distributed—both assumptions are often violated in real data. Permutation-based methods can help to overcome some of these limitations and provide more realistic thresholds for the discovery of true associations. Still, in practice, they are rarely implemented due to the high computational complexity.ResultsWe propose permGWAS, an efficient LMM reformulation based on 4D tensors that can provide permutation-based significance thresholds. We show that our method outperforms current state-of-the-art LMMs with respect to runtime and that permutation-based thresholds have lower false discovery rates for skewed phenotypes compared to the commonly used Bonferroni threshold. Furthermore, using permGWAS we re-analyzed more than 500 Arabidopsis thaliana phenotypes with 100 permutations each in less than 8 days on a single GPU. Our re-analyses suggest that applying a permutation-based threshold can improve and refine the interpretation of GWAS results.Availability and implementation permGWAS is open-source and publicly available on GitHub for download: https://github.com/grimmlab/permGWAS.Supplementary information Supplementary data are available at Bioinformatics online.

Rothia santali sp. nov., endophytic bacteria isolated from sandalwood (Santalum album L.) seedling.

A novel, mustard yellow-pigmented aerobic bacterial strain designated AR01T was isolated from hypocotyl tissue of a sandalwood seedling from Bangalore, India. The 16S rRNA gene of strain AR01T had the highest 98.97% sequence similarity with Rothia halotolerans YIM 90716T (KCTC 19172) followed by Rothia kristinaePM 129T (NBRC 15354T) (97.31%) andRothia koreensisP31T (JCM 15915) (97.11%), respectively. The strain AR01T was coccoid-shaped, non-motile, non-spore forming, oxidase negative and catalase positive. The strain AR01T has a genome size of 3.31Mb containing 2993 protein-coding genes including 48 tRNA and 10 rRNAs spread across 84 contigs. The genomic DNA G + C content was 71.77mol%. The calculated dDDH was 31.10% and the OrthoANI value was 85.27% when compared with its closest related type strain Rothia halotolerans YIM 90716T. The predominant cellular fatty acids were C16:0 iso, C15:0 anteiso and C17:0 anteiso. The strain AR01T contains major polar lipids including diphosphatidylglycerol and phosphatidylglycerol. The distinct physiological, biochemical characteristics and genotypic relatedness indicated that AR01T represents a novel species of the genus Rothia, for which the name Rothia santali sp. nov. (Type strain AR01T = MCC 4800T = JCM 35593T) is proposed.

RS12574989 and haplotype associated with α/β-chain imbalance and population HbA2 reduction

Determining the associated relationship of genotype and phenomenon would benefit the understanding of disease and renew disease intervention means. 14,518 patients who underwent haemoglobin electrophoresis from June 2020 to December 2020 were enrolled in our study, and additional data including sex, age and routine blood examination results were collected. We focused on individuals with normal red blood cell indices and no common thalassemia pathogenic mutation and selected three groups for the following study: the control group (2.5% ≤ HbA2 ≤ 3.5%), the HbA2 under 2.5 group (HbA2 < 2.5%) and the HbA2 under 2.4 group (HbA2 < 2.4%). Four regions of β-globin regulation were sequenced. Statistical analysis was conducted to compare the collected information of the three groups and the genotype distributions in the control group and sequenced group. The HbA2 under 2.5 group was characterized by a majority of females and lower red blood cell counts and haemoglobin compared with the control group. There were genotypes associated with the grouping as the T of rs12574989 and TTTAGC of the haplotype were significantly increased in the HbA2 under 2.4 group and CTTAGC was significantly decreased in the HbA2 under 2.4 group. This study demonstrated that the genotypes of the population associated with HbA2 were reduced in southern China.

Modeling MEN1 with Patient-Origin iPSCs Reveals GLP-1R Mediated Hypersecretion of Insulin.

Multiple endocrine neoplasia type 1 (MEN1) is an inherited disease caused by mutations in the MEN1 gene encoding a nuclear protein menin. Among those different endocrine tumors of MEN1, the pancreatic neuroendocrine tumors (PNETs) are life-threatening and frequently implicated. Since there are uncertainties in genotype and phenotype relationship and there are species differences between humans and mice, it is worth it to replenish the mice model with human cell resources. Here, we tested whether the patient-origin induced pluripotent stem cell (iPSC) lines could phenocopy some defects of MEN1. In vitro β-cell differentiation revealed that the percentage of insulin-positive cells and insulin secretion were increased by at least two-fold in MEN1-iPSC derived cells, which was mainly resulted from significantly higher proliferative activities in the pancreatic progenitor stage (Day 7–13). This scenario was paralleled with increased expressions of prohormone convertase1/3 (PC1/3), glucagon-like peptide-1 (GLP-1), GLP-1R, and factors in the phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway, and the GLP-1R was mainly expressed in β-like cells. Blockages of either GLP-1R or PI3K significantly reduced the percentages of insulin-positive cells and hypersecretion of insulin in MEN1-derived cells. Furthermore, in transplantation of different stages of MEN1-derived cells into immune-deficient mice, only those β-like cells produced tumors that mimicked the features of the PNETs from the original patient. To the best of our knowledge, this was the first case using patient-origin iPSCs modeling most phenotypes of MEN1, and the results suggested that GLP-1R may be a potential therapeutic target for MEN1-related hyperinsulinemia.

Longitudinal observation of meticillin-resistant Staphylococcus pseudintermedius pulsotypes in six veterinary hospitals in the north-western United States.

BackgroundMeticillin‐resistant Staphylococcus pseudintermedius (MRSP) infections in companion animals are increasing and are difficult to treat. Environmental contamination with MRSP in small animal primary care hospitals may pose an exposure risk to animal patients.MethodsThis longitudinal study assessed the genotypic relationships of MRSP isolated from 39 environmental samples collected from six private small animal primary care hospitals, in the north‐eastern United States, between August 2018 and April 2019.ResultsOf the 39 bacterial isolates, 18 unique pulsotypes were identified based on pulsed‐field gel electrophoresis, including six clusters of two or more indistinguishable isolates. Single pulsotypes were frequently detected from multiple hand‐contact and animal‐contact surfaces within a hospital during a single sampling event, but detection of a single pulsotype within the same hospital on subsequent visits was infrequent. However, one pulsotype was recovered from three separate hospitals, which suggests that either MRSP transmission between hospitals may have occurred via people, animals, or fomites or that there was a dominant community strain.ConclusionsSingle strains of MRSP were isolated from various hand‐contact and animal‐contact surfaces within hospitals, indicating the important role of humans, animals and the environment in MRSP transmission. Additionally, the detection of a single strain between hospitals and over time suggests that either MRSP transmission between hospitals may have occurred via people, animals or fomites or that there was a dominant community strain.

Molecular epidemiology of Coxiella burnetii detected in humans and domestic ruminants in Turkey

Q fever is a zoonotic disease that is known to be widespread throughout the world by many researches since its discovery in 1935 and it is important in terms of animal and public health. Coxiella burnetii, which is the etiological agent of the disease, is an obligate intracellular pathogen. While the disease generally manifests itself with abortion in animals, disease manifests as atypical pneumonia or granulomatous hepatitis in the acute form and as endocarditis in the chronic form in humans. Its presence in Turkey has been shown with a large number of studies. The aim of this study was to show the genotypic relationship with MLVA analysis of C. burnetii samples found in cattle, sheep and goat samples in Erzurum and Samsun Veterinary Control Institutes and blood samples collected from humans with atypical pneumonia findings. In the study, MLVA analyses of 100 positive samples from 50 cows, 41 sheep and 9 goats from Northeast Anatolia and Black Sea regions and C. burnetii positive samples found in 6 individuals with atypical pneumonia were performed. As a result of the study, it was found that 106 C. burnetii samples had belong to 16 genotype groups. It was found that genotype XVI was the most prevalent among these groups and it was seen in both regions. In addition to this, genotype IX profile was the second largest group with 83.3% (5/6) of human samples. In this study, the genotypes common in the regions were determined and a data source was created for possible outbreaks.

Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

SummaryBackgroundWhole-genome sequencing (WGS) of Mycobacterium tuberculosis complex has become an important tool in diagnosis and management of drug-resistant tuberculosis. However, data correlating resistance genotype with quantitative phenotypic antimicrobial susceptibility testing (AST) are scarce.MethodsIn a prospective multicentre observational study, 900 clinical M tuberculosis complex isolates were collected from adults with drug-resistant tuberculosis in five high-endemic tuberculosis settings around the world (Georgia, Moldova, Peru, South Africa, and Viet Nam) between Dec 5, 2014, and Dec 12, 2017. Minimum inhibitory concentrations (MICs) and resulting binary phenotypic AST results for up to nine antituberculosis drugs were determined and correlated with resistance-conferring mutations identified by WGS.FindingsConsidering WHO-endorsed critical concentrations as reference, WGS had high accuracy for prediction of resistance to isoniazid (sensitivity 98·8% [95% CI 98·5–99·0]; specificity 96·6% [95% CI 95·2–97·9]), levofloxacin (sensitivity 94·8% [93·3–97·6]; specificity 97·1% [96·7–97·6]), kanamycin (sensitivity 96·1% [95·4–96·8]; specificity 95·0% [94·4–95·7]), amikacin (sensitivity 97·2% [96·4–98·1]; specificity 98·6% [98·3–98·9]), and capreomycin (sensitivity 93·1% [90·0–96·3]; specificity 98·3% [98·0–98·7]). For rifampicin, pyrazinamide, and ethambutol, the specificity of resistance prediction was suboptimal (64·0% [61·0–67·1], 83·8% [81·0–86·5], and 40·1% [37·4–42·9], respectively). Specificity for rifampicin increased to 83·9% when borderline mutations with MICs overlapping with the critical concentration were excluded. Consequently, we highlighted mutations in M tuberculosis complex isolates that are often falsely identified as susceptible by phenotypic AST, and we identified potential novel resistance-conferring mutations.InterpretationThe combined analysis of mutations and quantitative phenotypes shows the potential of WGS to produce a refined interpretation of resistance, which is needed for individualised therapy, and eventually could allow differential drug dosing. However, variability of MIC data for some M tuberculosis complex isolates carrying identical mutations also reveals limitations of our understanding of the genotype and phenotype relationships (eg, including epistasis and strain genetic background).FundingBill & Melinda Gates Foundation, German Centre for Infection Research, German Research Foundation, Excellence Cluster Precision Medicine of Inflammation (EXC 2167), and Leibniz ScienceCampus EvoLUNG.

Genetic diversity, trait association and cause effect analysis in selected genotypes of finger millet [Eleusine coracana (L.) Gaertn.

Aim: The present investigation was planned to evaluate the finger millet genotypes for genetic variability, genotypic relatedness, an association between traits, and their direct effect on increasing grain and fodder yield. Methodology: The present investigation was planned to evaluate the finger millet genotypes for genetic variability, genotypic relatedness, an association between traits, and their direct effect on increasing grain and fodder yield. Results: Analysis revealed a high genotypic coefficient of variation (GCV) to the number of productive tillers per plant (57.98%), grain yield per plot (49.38%), number of heads per plot (49.27%) and number of fingers per head (45.54%). High heritability coupled with high genetic advance as percent of mean was observed for the number of heads per plot. Grain yield exhibited a significantly high positive correlation with fodder yield per plant (rg: 0.98), number of heads per plot (rg: 0.89) and harvest index (rg: 0.78). Fodder yield per plant, harvest index, single head weight, number of heads per plot and days to final harvest had a high direct positive effect on grain yield. The PCA separated total genetic variation into six components and covered almost 85.0% of genetic variation. Genotypes were grouped into four main groups and several subgroups based on Euclidean distances. Interpretation: The higher magnitude of GCV, heritability coupled with high genetic advance for a trait of interest; strong correlation between dependent and independent traits would be desirable for productivity enhancement in finger millet. The additive gene effect would also be rewarding by direct phenotypic selection.

Character Interrelationship and Principle Component Analysis of Some Black Gram (Vigna mungo L. Hepper) Genotypes under Moisture Stress Deficit Environment

Two pot experiments were conducted with ten black gram genotypes during winter in the net house of the Department of Plant Breeding and Genetics, Assam Agricultural University, Assam. The present experiment was conducted to assess the character interrelationship and grouping of genotypes based on their performance under water stress. The experiment was conducted in a controlled environment in a complete randomized block design with three replications and two environments (Non-stress &amp; Stress environments). The plant was exposed to drought stress during the first flower bud initiation (i.e., 33 days after sowing). The genotypes were screened on the basis of the results of multivariate analysis viz., pearson correlation, path analysis, modified path analysis, cluster analysis based on usual Euclidean distance and principal component analysis. The Pearson correlation, path analysis and modified path analysis identified the proline content and pod per plant as the critical yield determinants under both the environments. Besides, other significant yield contributing traits for water deficit stress were leaf area, chlorophyll content, pod length and seeds per pod. Usual Euclidean distance-based clustering categorized the genotypes into three groups with substantial variation in cluster composition of both stress and non-stress environment. Based on the relationship of characters and genotypes to the PC 1, it can be concluded that the genotypes AKU 10-6 and SBC 40 can be selected for Number of seeds per pod, Chlorophyll content, number of pods per plant and grain yield per plant characters for breeding purposes in both the environments.

The 283 А&gt;G (BsmI) VDR gene polymorphism as a predictor of osteoporosis complicated by chronic pyelonephritis in aluminum production workers

Introduction. In the structure of the morbidity of workers in the aluminum industry the leading place are occupied by bone and joint pathology and disorders of mineral metabolism, caused by prolonged exposure to toxic fluoride compounds. The study of the molecular genetic basis for the development of changes in bone metabolism and concomitant pathology of the kidneys in chronic occupational intoxication with fluorine compounds will make it possible to establish an associative relationship between the polymorphism of certain genes and the likelihood of developing these diseases. The aim of the study was to determine the significance of detecting BsmI VDR polymorphism as a predictor of osteoporosis associated with chronic kidney disease in workers of the main professions of aluminum production on the basis of clinical and genetic analysis. Materials and methods. Based on molecular-genetic and clinical methods, a comprehensive study of the prevalence of fluorine osteopathy was carried out with the determination of bone density parameters in 217 workers in the main professions of aluminum smelting under conditions of chronic exposure to high doses of fluorine on the body and in the comparison group (57 individuals) without occupational pathology. Results. When examining workers, it was established that the frequency of registration of BsmI VDR polymorphism genotypes corresponded to the Hardy-Weinberg law. It was determined that the GG VDR genotype is a predictor of osteoporosis (p=0,0034), and carriers of the AA genotype are resistant to its development (p=0,0001). An associative relationship of the heterozygous AG VDR genotype with the development of chronic occupational intoxication with fluorine compounds was revealed (p=0,0232). It has been shown that osteoporosis associated with chronic kidney disease is associated with the G allele of the GG VDR genotype. Conclusions. In the structure of professional pathology of metallurgists employed in the production of aluminum, against the background of hyperplastic changes in bone tissue due to an increase in its mass, there is a significant decrease in mineral density (p=0,0047). The allelic specificity of the VDR gene associated with the development of toxic osteopathies was revealed. The GG genotype is associated with the development of osteoporosis. A high degree of association of the AG genotype (p=0,0232) with fluoride intoxication was shown. Osteoporosis associated with chronic kidney disease is associated with the GG VDR genotype and the G allele of the 283 A&gt;G (BsmI) VDR polymorphism, which determines progressive disorders of mineral metabolism and aggravates the course of fluorosis in workers. Ethics. The examination of aluminum production workers was carried out in the hospital of the Research Institute for Complex Problems of Hygiene and Occupational Diseases in strict accordance with the ethical principles of conducting scientific and medical research with human participants, developed on the basis of the Helsinki Declaration by the World Medical Association "Ethical principles of conducting scientific medical research with human participants" with amendments of 2013, "Rules of Clinical Practice in the Russian Federation" approved by the Order of the Ministry of Health of the Russian Federation No. 266 dated 06/19/2003. The collection of clinical history data was carried out during an oral questionnaire face to face with a written informed consent to participate in the study and analysis of medical histories according to 025/u-87 form.

EVALUATION OF WHEAT GENOTYPES: GENOTYPE × ENVIRONMENT INTERACTION AND GGE BIPLOT ANALYSIS

This research was carried out to evaluate the grain yield, yield traits and some quality characteristics of 18 bread wheat genotypes in seven different locations in Thrace region using principal component analysis and genotype + genotype × environment interaction (GGE) biplot analysis to determine the genotypes with high yield and desired quality characteristics during the 2016-2017 and 2017-2018 cropping years. The experiments were arranged in a randomized complete block design with four replications. Genotype, environment and genotype × environment interactions were found statistically significant at p≤0.01 level for all investigated traits. Mean values of the genotypes varied between 4841-6807 kg ha-1 for grain yield, 118.6-131.6 days for heading date, 80.4-104.7 cm for plant height, 7.7-10.4 cm for spike length, 16.4-20.3 for number of spikelets per spike, 16.4-20.3 number of grains per spike, 1.49-2.41 g grain weight per spike, 72-77.8 kg hl-1 for test weight and 36.6-45.3 g for thousand kernel weight. Principal component biplot analyzes explained the relationships between the investigated traits and genotypes at a ratio of 60.9%. It was observed that there was a positive and significant relationship between grain yield and test weight, a negative relationship with grain yield and spike length and grain weight per spike. GGE biplot analysis explained 82.65% of the relationship of genotype + genotype x environment for grain yield. According to the GGE biplot analysis two mega environments were determined and Lucilla and Glosa genotypes took place in the biggest mega environment consisted of four environments as superior genotypes.

Genomic and Evolutionary Analysis of Salmonella enterica Serovar Kentucky Sequence Type 198 Isolated From Livestock In East Africa.

Since its emergence in the beginning of the 90’s, multidrug-resistant (MDR) Salmonella enterica subsp. enterica serovar Kentucky has become a significant public health problem, especially in East Africa. This study aimed to investigate the antimicrobial resistance profile and the genotypic relatedness of Salmonella Kentucky isolated from animal sources in Ethiopia and Kenya (n=19). We also investigated population evolutionary dynamics through phylogenetic and pangenome analyses with additional publicly available Salmonella Kentucky ST198 genomes (n=229). All the 19 sequenced Salmonella Kentucky isolates were identified as ST198. Among these isolates, the predominant genotypic antimicrobial resistance profile observed in ten (59.7%) isolates included the aac(3)-Id, aadA7, strA-strB, bla TEM-1B, sul1, and tet(A) genes, which mediated resistance to gentamicin, streptomycin/spectinomycin, streptomycin, ampicillin, sulfamethoxazole and tetracycline, respectively; and gyrA and parC mutations associated to ciprofloxacin resistance. Four isolates harbored plasmid types Incl1 and/or Col8282; two of them carried both plasmids. Salmonella Pathogenicity islands (SPI-1 to SPI-5) were highly conserved in the 19 sequenced Salmonella Kentucky isolates. Moreover, at least one Pathogenicity Island (SPI 1–4, SPI 9 or C63PI) was identified among the 229 public Salmonella Kentucky genomes. The phylogenetic analysis revealed that almost all Salmonella Kentucky ST198 isolates (17/19) stemmed from a single strain that has accumulated ciprofloxacin resistance-mediating mutations. A total of 8,104 different genes were identified in a heterogenic and still open Salmonella Kentucky ST198 pangenome. Considering the virulence factors and antimicrobial resistance genes detected in Salmonella Kentucky, the implications of this pathogen to public health and the epidemiological drivers for its dissemination must be investigated.

Outcomes and genotype correlations in patients with mitochondrial trifunctional protein or isolated long chain 3-hydroxyacyl-CoA dehydrogenase deficiency enrolled in the IBEM-IS database

PurposeMitochondrial trifunctional protein deficiency (TFPD) and isolated long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) are two related defects of fatty acid β -oxidation. While NBS has decreased mortality, morbidity remains significant. Additionally, the relationship of genotype to clinical outcome remains unclear. To better understand these issues, we collected natural history data for these conditions by reviewing seven years of retrospective data from 45 cases of TFPD or LCHADD in the Inborn Errors of Metabolism – Information System. MethodsAvailable data included age at database entry, last datapoint, and development of various complications. Data were analyzed by clinical assigned diagnosis (LCHADD or TFPD), subdivided by method of ascertainment (newborn screening-NBS, or other than by newborn screening-NNBS), then re-analyzed based on four genotype groups: homozygous c.1528GC (p.E510Q) (common LCHAD variant); heterozygous c.1528GC (p.E510Q), other HADHA variants; and HADHB variants. ResultsForty-five patients from birth to 34 years of age were analyzed by assigned diagnosis (30 LCHADD and 15 TFPD) and method of ascertainment. Thirty had further analysis by genotype (22 biallelic HADHA variants and 8 biallelic HADHB variants). With regards to maternal complications, retinopathy, cardiomyopathy and hypoglycemia, patients with biallelic HADHA variants (with or without the common LCHAD variant) manifest a traditional LCHADD phenotype, while those with HADHB gene variants more commonly reported neuromusculoskeletal type TFPD phenotype. While retinopathy, rhabdomyolysis and peripheral neuropathy tended to present later in childhood, many features including initial report of cardiomyopathy and hypoglycemia presented across a wide age spectrum. ConclusionThis study demonstrates the utility of genotypic confirmation of patients identified with LCHADD/TFPD as variants in the HADHA and HADHB genes lead to different symptom profiles. In our data, biallelic HAHDA variants conferred a LCHADD phenotype, regardless of the presence of the common LCHAD variant.

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension

Rationale and objectiveAPOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. Study designMulticenter, pragmatic, randomized controlled clinical trial. Setting and participants6650 individuals with African ancestry and hypertension from 13 health systems. InterventionAPOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. OutcomesBlood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. ResultsTo date, the trial has enrolled 3423 participants. ConclusionsThe effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record. Trial registrationClinicalTrials.govNCT04191824

Genetic Structure of Native Blue Honeysuckle Populations in the Western and Eastern Eurasian Ranges.

Blue honeysuckle (Lonicera caerulea L.) is a promising berry crop producing edible early-ripening berries with a valuable chemical composition. We evaluated the genetic diversity of native L. caerulea populations from the western (Baltic states) and eastern (the Russian Far East and Japan) edges of the Eurasian range using inter-simple sequence repeat (ISSR) and chloroplast DNA (psbA-trnH and trnL-trnF) markers. The genetic relationships of populations and genotypes were analyzed using principal coordinate and cluster analyses (neighbor joining and Bayesian clustering). Sampling was carried out in two disjunct areas of this circumpolar species and the analyses showed clustering of individuals and populations according to geographic origin. The analysis of genetic structure based on ISSR markers showed that the studied populations of L. caerulea were highly differentiated. However, sequence analysis of two chloroplast DNA (cpDNA) regions revealed no phylogeographic structure among the populations. We also found that the eastern populations of blue honeysuckle had significantly greater genetic diversity parameters than the populations from the Baltic region. This finding correlates with the endangered status of blue honeysuckle in the Baltic states.

The relationship of maternal rank, 5-HTTLPR genotype, and MAOA-LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta).

Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as "biological." Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3- to 4-month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their mothers in large, outdoor, half-acre cages. Maternal rank was defined as the proportion of animals outranked by each female, and the two genes of interest to us were monoamine oxidase and serotonin transporter, both of which are polymorphic in their promoter regions (MAOA-LPR and 5-HTTLPR, respectively), with one allele of each gene considered a "plasticity" allele, conferring increased sensitivity to environmental events. Our large sample size (n = 2014-3140) enabled us to examine the effects of individual genotypes rather than combining genotypes as is often done. Rank was positively associated with Confident temperament, but only for animals with the 5-repeat allele for MAOA-LPR. Rank had no other effect on temperament. In contrast, genotype had many different effects, with 5-HTTLPR associated with behavioral inhibition, and MAOA-LPR associated with ratings-based measures of temperament. We also examined the joint effect of the two genotypes and found some evidence for a dose-response: animals with the plasticity alleles for both genes were more likely to be behaviorally inhibited. Our results suggest phenotypic differences between animals possessing alleles for MAOA-LPR that show functional equivalence based on in vitro tests, and our data for 5-HTTLPR revealed differences between short/short homozygotes and long/short heterozygotes, strongly suggesting that combining genotypes for statistical analysis should be avoided if possible. Our analysis also provides evidence of sex differences in temperament, and, to our knowledge, the only evidence of differences in temperament based on specific pathogen-freestatus. We suggest several directions for future research.

Field screening of diverse wheat germplasm for determining their adaptability to semi-arid climatic conditions.

Wheat (Triticum aestivum L.) is an important staple food crop for one third of global population and important crop for securing future food security. Rapid changes in the climate on global scale could be a threat for future food security. This situation urges plant breeders to explore the genetic potential of existing wheat germplasm. This study screened forty diverse wheat genotypes for their yield under two different agroclimatic conditions, i.e., Layyah and Dera Ghazi Khan, Pakistan. Data relating to plant height, peduncle length, flag leaf area, spike length, number of spikelets, number of grains per spike, thousand grain weight, chlorophyll content and grain yield were recorded. The tested wheat genotypes significantly differed for grain yield and related traits. Grain yield was positively correlated with plant height, spike length, spike number, flag leaf length, number of grains per spike, and 1000-grain weight. Biplot obtained from the cluster analysis by Euclidean method grouped the studied genotypes in 3 different groups. The genotypes exhibited 10.77% variability within quadrants, whereas 72.36% variability was recorded between quadrants according to clustering. Dendrogram grouped the tested genotypes into two main clusters. The main cluster “I” comprised of 2 genotypes, i.e., ‘Seher-2006’ and ‘AS-2002’. The cluster “II” contained 38 genotypes based on Euclidian values. Genotypes within same cluster had smaller D2 values compared to those belonging to other clusters. The genetic relationships of genotypes provide useful information for breeding programs. Overall, the results revealed that genotypes ‘Line 9733’, ‘Bhakar-2002’, ‘Line A9’ and ‘SYN-46’ had better yield and yield stability under climatic conditions of southern Punjab. Therefore, these genotypes could be recommended for general cultivation in the study region.

Deep learning based on biologically interpretable genome representation predicts two types of human adaptation of SARS-CoV-2 variants

Explosively emerging SARS-CoV-2 variants challenge current nomenclature schemes based on genetic diversity and biological significance. Genomic composition-based machine learning methods have recently performed well in identifying phenotype–genotype relationships. We introduced a framework involving dinucleotide (DNT) composition representation (DCR) to parse the general human adaptation of RNA viruses and applied a three-dimensional convolutional neural network (3D CNN) analysis to learn the human adaptation of other existing coronaviruses (CoVs) and predict the adaptation of SARS-CoV-2 variants of concern (VOCs). A markedly separable, linear DCR distribution was observed in two major genes—receptor-binding glycoprotein and RNA-dependent RNA polymerase (RdRp)—of six families of single-stranded (ssRNA) viruses. Additionally, there was a general host-specific distribution of both the spike proteins and RdRps of CoVs. The 3D CNN based on spike DCR predicted a dominant type II adaptation of most Beta, Delta and Omicron VOCs, with high transmissibility and low pathogenicity. Type I adaptation with opposite transmissibility and pathogenicity was predicted for SARS-CoV-2 Alpha VOCs (77%) and Kappa variants of interest (58%). The identified adaptive determinants included D1118H and A570D mutations and local DNTs. Thus, the 3D CNN model based on DCR features predicts SARS-CoV-2, a major type II human adaptation and is qualified to predict variant adaptation in real time, facilitating the risk-assessment of emerging SARS-CoV-2 variants and COVID-19 control.

Relationship of β-casein genotypes (A1A1, A1A2 and A2A2) to the physicochemical composition and sensory characteristics of cows’ milk

ABSTRACT This study determines the relationship between β-casein CSN2 genotypes (A1A1, A1A2, A2A2) and milk’s biochemical and sensory traits. Ninety-six cow’s milk from the same herd was investigated. Animals were grouped according to the β-casein genotype variants A1A1, A1A2 and A2A2, with thirty-two animals each. A1A1 milk had higher monounsaturated fatty acids MUFA (<0.001) and lower levels of saturated fatty acids SFA (<0.001) fatty acids content. A1A2 milk had higher amino acids and higher SFA (<0.001) fatty acid content in the milk. Furthermore, A1A2 milk had the highest lightness index (L*) (<0.001), which we found correlated to increased redness index (a*) (<0.001) and yellowness index (b*) (<0.01) values. A2A2 milk was higher in polyunsaturated fatty acids PUFA (<0.001), omega-3 (0.001) and omega-6 (<0.001) and lower saturated fatty acids SFA (<0.001) fatty acids content. We concluded that the amino acid content, fatty acid content and colour of the milk could be influenced by CSN2 genotypes A1A1, A1A2 and A2A2. As a result, the selective breeding of genotypes with preferred qualities may improve milk and dairy products.

Association of Promoter Polymorphism of MMP-1 rs1799750 and MMP-3 rs3025058 with circulating levels of MMP-1 and MMP-3 in patients with Rheumatoid Arthritis

The genetic background of Rheumatoid arthritis (RA) is only partly understood and several genes seem to be involved. Matrix metalloproteinases (MMPs) are involved in joint destruction in rheumatoid arthritis (RA). MMP1 (interstitial collagenase) and MMP3 (stromelysin 1) as most studied enzymes in RA. In the present study, we have investigated the genotypic and haplotypic relationships of the MMP-1 and MMP-3 genes with circulating levels of these MMPs. Functional relevance in single-nucleotide polymorphisms (SNPs)in rs1799750 (1G/2G, MMP-1 promoter) and rs3025058 (5A/6A, MMP-3 promoter) genotyped in 60 RA patients and 60 healthy control is used to determine association of polymorphisms with the severity of the disease. The MMP-3 SNPs were associated with serum MMP-3 level (P &lt;0.05) and were associated with disease activity score (DAS28). We observed that MMP-1 SNPs were lacking in association with disease activity. Our findings conclude that several closely linked polymorphisms in the MMP-1–MMP-3 loci have an important role in determining the circulating levels of these MMPs in RA and that MMP-3 polymorphism is associated with the disease severity.