Allele Frequencies Research Articles

CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin

BackgroundA single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians.ObjectiveThis research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians.MethodsIn this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes.ResultsThe allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations.ConclusionsThe CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin.Graphical

Evaluation of population genetics of Moringa oleifera Provenances from Coastal Kenya using Single Nucleotide Polymorphism (SNPs) markers

Population genetics analysis is a prerequisite to understanding how and why genotypes and allele frequencies and change over time between and within populations. Consequently, it offers insight into the process of evolutionary change and makes it possible to map variants linked to traits that differ among populations. In the present study, Single Nucleotide Polymorphisms (SNPs) markers were utilized to study the genetic characterization of 17 provenances from the Coast region of Kenya. 164 genotypes of Moringa oleifera were selected from 17 populations and genome sequencing undertaken utilizing genotyping by sequencing (GBS). Identification of polymorphisms (SNP Calling) in the selected genotypes and population genetic studies were carried out. SNP calling was done by Illumina’s SNP caller algorithm in the CASAVA software. 20,921 SNPs were called with an average call rate of 0.82. Average polymorphsm content (PIC) for the SNPs was 0.24 and reproducibility was 0.98. A phenetic tree was constructed using a neighbor-joining approach using DArT R. For the population genetics analysis, F statistic (Fst) utilising the functions StAMPP package in DArT R was performed whereby Gede and Samburu exhibited the least heterozygosity/correlation with a value of 0.0003 whereas Pwani University and Samburu had the highest correlation of genes at 0.37. Euclidean was used as a measure distance, and the average distance between the populations was 33.024. The molecular variance analysis (AMOVA) described a lower, 2.55%, variation within the population and 2.73% among the populations. The high similarity between the genotypes could be attributed to the Moringa plants in the various provenances having the same ancestry. This study may help identify links between gene allelic forms and phenotypes, allowing the alleles to be connected to desired characteristics such as rapid growth and high yield (functional analysis), because of the high frequency of SNPs and their role as a source of allele variations.

Analysis of cis-regulatory changes underlying phenotype divergence shaped by domestication in pigs

BackgroundCis-regulatory elements (CREs) are regions of DNA that regulate the expression of nearby genes. Changes in these elements can lead to phenotypic variations and adaptations in different populations. However, the regulatory dynamics underlying the local adaptation of traits remain poorly understood in Chinese and Western pigs. By comparing the chromatin accessibility profiles of skeletal muscle, liver, and fat between these two pig populations, we aimed to identify key regulatory elements that could explain phenotypic differences observed between the two groups.ResultsOur results revealed that the genome-wide chromatin accessibility profiles were largely similar at a qualitative level within tissues. However, we also identified local regions that exhibited quantitative differences, most of which occurred in liver tissue. Interestingly, we found that most of the increased chromatin accessibility in the livers of Chinese pigs was associated with tissue-specific openness. Furthermore, we observed a positive correlation between the ATAC-seq signal at the transcript start site (TSS) and the expression levels of nearby genes. Motif enrichment analysis revealed NR2F1 as a key regulator in Chinese pigs. Differentially expressed genes (DEGs) in Chinese pigs showed enrichment for NR2F1 response targets. One of the genes regulated by NR2F1 in Chinese pigs, NPC1, harbored a high alternative allelic frequency in the intron region.ConclusionOverall, our study provides valuable insights into the regulatory dynamics underlying phenotypic variation in pigs. By elucidating the role of CREs in driving phenotypic variation, we can better understand the genetic basis of complex traits and potentially identify targets for genetic improvement in livestock breeding programs.

Developmental Validation of a DIP-InDel/DIP-STR System for the Detection of Unbalanced DNA Mixtures.

Extracting "masked" minor donor information from an unbalanced DNA mixture stain is important for the identification of the person of interest. In recent years, a series of compound markers genotyped based on allele-specific amplifications have been proposed to detect minor contributors of mixed stains. In this study, we selected out 18 DIP-InDel markers from previous literatures and established a multiplex system encompassing 18 DIP-InDel markers and 6 DIP-STR markers in two separate reactions. The allele frequencies were estimated based on 200 samples, and 23 of the 24 DIP-linked length polymorphic markers had a relatively high probability of informative markers (I value >0.267), which indicated their potential usefulness in the Chinese Han population. Moreover, the multiplex was highly sensitive (requiring >0.025ng) and specific to human DNA. This system is capable of detecting the minor contributor comprising 1% in unbalanced mixtures of two individuals. The capacity of profiling cell-free DNA was also analyzed in few cases. At least one paternal allele could be detected in maternal plasma samples with gestation periods ranging from 27 to 40 weeks. To conclude, the DIP-linked length polymorphic markers may serve as a convenient method for detecting the presence of a minor donor in unbalanced mixtures and show promise for noninvasive prenatal diagnosis.

Knockdown resistance in Stomoxys calcitrans stable fly populations on German dairy farms: kdr alleles explain susceptibility of individual flies to deltamethrin

AbstractThe stable fly, Stomoxys calcitrans, is a globally important pest causing stress, economic losses and transmission of pathogens in livestock. Control on commercial farms relies predominantly on the use of insecticides, with pyrethroids being the most frequently used class of insecticides in industrialised countries. Here, laboratory isolates were obtained from four dairy farms in Brandenburg (Germany) and tested for phenotypic resistance to deltamethrin in comparison to a susceptible reference isolate using topical application. Individual flies were subsequently genotyped using allele-specific real-time PCRs. Phenotypic resistance was observed in all four field isolates with resistance ratios between 46 and 119 compared to the susceptible laboratory strain. At position 1014 of the voltage-sensitive sodium channel, allele-specific PCRs detected the wild-type, kdr-his and kdr genotypes encoding leucine, histidine and phenylalanine, respectively. In the susceptible laboratory isolate, only the wild-type was identified. On the farms with very high LD50 values, the kdr variant was most prevalent and logistic regression analysis revealed that the kdr variant increased the odds to survive exposure to deltamethrin more than the kdr-his genotype. Flies carrying two resistance alleles were less susceptible than flies that also carried one wild-type allele. In three out of four field isolates, the allele frequencies were significantly different from the expectations of the Hardy–Weinberg equilibrium suggesting ongoing selection. The data show that the phenotype can be largely explained by the kdr genotype and represent high frequencies of the L1014F kdr and L1014H kdr-his variants conferring high levels of resistance in northern Germany.

A spectrum of nonsense-mediated mRNA decay efficiency along the degree of mutational constraint

Despite its importance for regulating gene expression, nonsense-mediated mRNA decay (NMD) remains poorly understood. Here, we extend the findings of a previous landmark study that proposed several factors associated with NMD efficiency using matched genome and transcriptome data from The Cancer Genome Atlas Program (TCGA) by incorporating additional data including Genotype-Tissue Expression (GTEx), gnomAD, and metrics for mutational constraints. Factors affecting NMD efficiency are analyzed using an allele-specific expression (ASE)-based measure to reduce noise caused by random variations. Additionally, by combining our data with the updated allele frequency database of gnomAD, we demonstrate the spectrum of NMD efficiency according to the degree of gene-level mutational constraints (degree of a gene-tolerating loss-of-function variants). The NMD prediction model, trained on TCGA data, shows that gene-level mutational constraint is an important predictor of NMD efficiency. Findings of this study suggest the potential role of NMD on shaping the landscape of mutational constraints.

First report on the diversity of domestic pigeons (Columba livia) using plumage coloration and patterning in Saravena, Arauca, Colombia

The domestic pigeon (Columba livia Gmelin, 1789), native to Africa and Eurasia, is extensively found across Europe, Western Asia, Africa, and the Americas. The pigeon (Columba livia) was domesticated several centuries ago and holds a privileged place as a symbol of peace, love, fidelity, and ornamentation in parks. In recent decades, an increase in the populations of these pigeons has been detected. The Spanish brought Columba livia to Colombia in the 15th century. The objective of this study was to evaluate the genetic diversity of the domestic pigeon using loci related to plumage coloration and patterning in Saravena. Random sampling was conducted in six colonies between March and April 2024. Through urban visits, direct observation, and photographic records, a phenotypic classification of each of the 580 pigeons from the different flocks studied was carried out. Autosomal markers associated with coloration and plumage were analysed: Grizzle, Spread, Checker, and the sex-linked locus Ash-Red. Genetic profiles were calculated using indices: allele frequency, genetic diversity, and population structure, estimated with the PopGene 1.31 program. Diversity was assessed using the FSTAT program. The dendrogram was constructed with the MEGA X program. The marker with the highest allele frequency was Grizzle (P=0.1834), while the Spread marker had the lowest values (P=0.0300). The highest HT value was 0.3002 for the Grizzle marker, GST showed figures of 0.0360, and gene flow was 20.6; the FIS and FIT statistics reported values of 0.2779 and 0.2848, and FIT was 0.0091. Moderate genetic diversity, a deficit of heterozygotes, and an excess of homozygotes were observed, along with low interpopulation genetic differentiation and high gene flow between subpopulations. Low genetic distance values were also found between the studied subpopulations. The populations are closely related genetically, which may be due to their geographical proximity, which has favoured genetic exchange.

Population size rescaling significantly biases outcomes of forward-in-time population genetic simulations.

Simulations are an essential tool in all areas of population genetic research, used in tasks such as the validation of theoretical analysis and the study of complex evolutionary models. Forward-in-time simulations are especially flexible, allowing for various types of natural selection, complex genetic architectures, and non-Wright-Fisher dynamics. However, their intense computational requirements can be prohibitive to simulating large populations and genomes. A popular method to alleviate this burden is to scale down the population size by some scaling factor while scaling up the mutation rate, selection coefficients, and recombination rate by the same factor. However, this rescaling approach may in some cases bias simulation results. To investigate the manner and degree to which rescaling impacts simulation outcomes, we carried out simulations with different demographic histories and distributions of fitness effects using several values of the rescaling factor, Ǫ, and compared the deviation of key outcomes (fixation times, allele frequencies, linkage disequilibrium, and the fraction of mutations that fix during the simulation) between the scaled and unscaled simulations. Our results indicate that scaling introduces substantial biases to each of these measured outcomes, even at small values of Ʈ. Moreover, the nature of these effects depends on the evolutionary model and scaling factor being examined. While increasing the scaling factor tends to increase the observed biases, this relationship is not always straightforward, thus it may be difficult to know the impact of scaling on simulation outcomes a priori. However, it appears that for most models, only a small number of replicates was needed to accurately quantify the bias produced by rescaling for a given Ʈ. In summary, while rescaling forward-in-time simulations may be necessary in many cases, researchers should be aware of the rescaling procedure's impact on simulation outcomes and consider investigating its magnitude in smaller scale simulations of the desired model(s) before selecting an appropriate value of Ʈ.

Pediatric pharmacogenetics: profiling CYP2C8 polymorphisms at King Abdulaziz University Dental Clinic.

Ibuprofen, a widely used non-steroidal anti-inflammatory (NSAID) for managing pain and inflammation in pediatric patients, is metabolized by the CYP2C8 enzyme. Studies suggest that the CYP2C8*2, *3, and *4 variations of the CYP2C8 gene diminish ibuprofen metabolism, increasing the risk of adverse reactions. The aim of this study was to determine the frequency of the CYP2C8*2, *3, and *4 alleles and genotypes in a pediatric population attending the King Abdulaziz University dental clinic and compare our findings to those of other populations. A cross-sectional study was conducted with 140 healthy Saudi children ages 6-12. Saliva samples were collected using Oragene™ DNA Sample Collection Kits and analyzed for polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study identified that CYP2C8*2 AA, AT, and TT genotypes occurred at frequencies of 87.86 %, 9.29 %, and 2.86 %, respectively. For CYP2C8*3, AA, AG, and GG genotypes were found in 87.14 , 8.75, and 4.29 % of subjects, respectively. The CYP2C8*4 allele was less frequent, with CC and CG genotypes at 97.86 % and 2.14 %, respectively, and the GG genotype was absent. Allele frequencies for CYP2C8*2, *3, and *4 were 7.5 %, 8.57 %, and 1.07 %, respectively. Our findings reveal that the allelic frequencies for the CYP2C8 polymorphisms in the Saudi pediatric cohort are substantially elevated compared to those reported in other Asian populations. This suggests Saudis may experience more varied drug responses, especially for medications that undergo metabolism by the CYP2C8 enzyme, like ibuprofen.

Investigating the Matrix of Factor V Leiden (G1691A), Factor II Prothrombin (G2021A), MTHFR C677T and A1298G Polymorphisms in Greek Population: A Preliminary Study

Background: Thrombophilia, characterized by an increased risk of thrombosis, can result from genetic polymorphisms in clotting factors. This study aims to investigate the prevalence of factor V Leiden (G1691A), factor II prothrombin (G20210A), and MTHFR (C677T and A1298C) polymorphisms in a Greek population, evaluating not only their association with thrombophilia, but also broader health implications. Methods: We conducted a cross-sectional study involving one hundred apparently healthy adults from Thessaloniki, Greece. After obtaining informed consent, DNA was isolated and analyzed using real-time PCR to detect the frequencies of the aforementioned polymorphisms. Results: The genetic distribution of the examined polymorphisms aligns closely with that observed in Northern Europe. Factor V Leiden (FVL) and prothrombin G20210A mutations were predominantly wild types, with a small percentage showing heterozygous mutations. The MTHFR C677T and A1298C polymorphisms showed a higher variation in allele frequency. Certain lifestyle factors such as smoking and high body mass index were significantly associated with the occurrence of combined MTHFR genotypes, suggesting an interaction between genetic and environmental risk factors. Family cancer and cardiovascular history was significantly associated with combined FVL and prothrombin G20210A and MTHFR polymorphism heterozygous carriers. Conclusions: Our findings indicate that these genetic polymorphisms are not only pivotal in understanding thrombophilia but also have broader implications for cardiovascular disease and cancer. This study highlights the need for further research into the combined effects of genetic and epigenetic factors on health, which could lead to improved screening and personalized preventive healthcare strategies.

Assessment and preservation of the gene pool of the domestic &lt;i&gt;Kholmogorsk&lt;/i&gt; cattle breed in the Arkhangelsk region

The article presents the results of monitoring immunogenetic studies on the origin of Kholmogory cattle to establish their breed genetic passport for the EAB locus of blood groups. The importance of determining of the breeding animals statute taking into account the forms of the identified state of erythrocyte antigens for the purpose of registration in the federal state information and analytical system of breeding resources of the Russian Federation is noted. In breeding farms of the Arkhangelsk region over the past 29 years, the total number of animals tested for the reliability of origin was 57,311. The percentage of reliability in the monitored livestock numbers varied from 86.95% (1995-2000) to 97.28% (2016-2020). To establish the genetic passport of breeding female tribal species of the breed with up to 75% Holstein bloodline approved for breeding purposes when working with Kholmogory cattle, we conducted immunogenetic testing, which revealed 46 alleles of the EAB locus. The total frequency of the EAB locus alleles in animals of groups 1-2 with specific (typical) for the Kholmogory breed and with unique alleles was 69.38%. In group 3 of animals with alleles of the approved Holstein breed, the total frequency was set at 30.6%, in group 4 with alleles of unapproved breeds – 0.02%. It was established that the concentration of alleles G2O2, B2O2, B2G2KA’B’G’O’G’’, B2E’2G’, B2O2Y2D’, Q is very low, they are found only in some individuals. The degree of homozygosity (theoretical) is 5.6%, the number of effective alleles is 17.9.

Applying a computer model to evaluate the evolution of resistance by western corn rootworm to multiple Bt traits in transgenic maize.

Western corn rootworm, Diabrotica virgifera virgifera (LeConte) (Coleoptera: Chrysomelidae), is a major pest of maize in the United States. Transgenic maize producing insecticidal toxins from the bacterium Bacillus thuringiensis (Bt) have been used to manage this pest since 2003. Refuges of non-Bt maize have been used to delay resistance to Bt maize by western corn rootworm, and are planted in conjunction with maize producing single or multiple (i.e., pyramids) Bt toxins. Two Bt toxins, Cry3Bb1 and Gpp34/Tpp35Ab1, were used individually before being combined as a pyramid, at which point resistance had already evolved to Cry3Bb1. Pyramids targeting western corn rootworm therefore contained at least one toxin to which resistance had evolved. Western corn rootworm has now evolved resistance to all four commercially available Bt toxins used for rootworm management. We used laboratory and field-generated data to parameterize a deterministic model to simulate the effectiveness of refuges and Bt pyramids to delay resistance to Bt maize in western corn rootworm. Resistance to the pyramid of Cry3Bb1 with Gpp34/Tpp35Ab1 evolved more rapidly when resistance to Cry3Bb1 was already present. This effect arose when model conditions affecting initial resistance allele frequency, inheritance of resistance, and fitness costs were varied. Generally, resistance evolved faster when initial resistance allele frequencies were higher, inheritance of resistance was nonrecessive, and fitness costs were absent, which is consistent with previous models that simulated resistance evolution. We conclude that new transgenic pyramids should pair novel, independently acting toxins with abundant refuges to minimize the risk of rapid resistance evolution.

Low nucleotide diversity of the Plasmodium falciparum AP2-EXP2 gene among clinical samples from Ghana.

PfAP2-EXP2 is located within chromosome 6 of Plasmodium falciparum recently identified to be undergoing an extensive selective sweep in West African isolates. The gene encoding this transcription factor, PfAP2-EXP2, is essential and thus likely subject to purifying selection that limits variants in the parasite population despite its genomic location. 72 Plasmodium falciparum field samples and 801 clinical sequences from the Pf6 MalariaGEN dataset of Ghanaian origin, were integrated and analysed. A total of 14 single nucleotide variants of which 5 were missense variants, were identified after quality checks and filtering. Except for one, all identified variants were rare among the clinical samples obtained in this study (Minor allelic frequency < 0.01). Further results revealed a considerably low dN/dS value (0.208) suggesting the presence of purifying selection. Further, all the mutant amino acids were wildtype residues in AP2-EXP2 orthologous proteins-tentatively suggesting a genus-level conservation of amino acid residues. Computational analysis and predictions corroborated these findings. Despite the recent extensive selective sweep within chromosome 6 of West African isolates, PfAP2-EXP2 of Ghanaian origin exhibits low nucleotide diversity and very low dN/dS consistent with purifying selection acting to maintain the function of an essential gene. The conservation of AP2-EXP2 is an important factor that makes it a potential drug target.

TP53 Mutation Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification Based on the 5th WHO and International Consensus Classification Criteria: A Korean Multicenter Study.

TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. This study included patients aged ≥ 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Diagnosing Monogenic Stroke at Younger Age.

An increasing number of monogenic conditions underlying stroke are being identified. We explored the possibilities of increasing the diagnostic yield of monogenic stroke in a population under 56 years of age. Fifty probands ≤55 years at their first stroke episode were characterized clinically and investigated by whole genome sequencing. Probands had one or more of: (1) one or more first to second degree relatives with stroke under 60 years or same stroke-causing condition/disease; (2) no hypertension, hypercholesterolemia, diabetes, heart disease, or smoking; or (3) either multiple stroke episodes or multiple arterial dissections. Variants with minor allele frequency under 0.01, identified by using our stroke gene panels, were assessed. The stroke subtypes, including large artery atherosclerotic, large artery nonatherosclerotic (tortuosity, dolichoectasia, aneurysm, nonatherosclerotic dissection, or occlusion), cerebral small vessel disease, cardioembolic (arrhythmia, heart defect, or cardiomyopathy), coagulation dysfunctions (venous thrombosis, arterial thrombosis, or bleeding tendency), intracerebral hemorrhage, vascular malformations (cavernoma or arteriovenous malformations), metabolic disorders, or cryptogenic embolic, were used for genotype-phenotype correlation. In a final step, we combined genetic and clinical information to determine if the genetic variant likely was the cause of stroke in the patients. Whole genome sequencing of younger patients with stroke identified 17 clinically matching genetic variants in 15 of 50 (30%) patients, while a stronger clinical correlation with stroke was established in only 6 (12%) of them. Stroke-related genetic variants were identified in 4 of 5 (80%) patients with cardioembolic stroke subtype, 3 of 4 (75%) with intracerebral hemorrhage, 7 of 18 (39%) with cryptogenic embolic stroke, 1 of 6 (17%) with small vessel disease, and 3 of 15 (20%) of patients with nonatherosclerotic large artery stroke, including 1 of 11 (9%) with cervical dissection stroke. Careful clinical interpretation of whole genome data using stroke gene panels can detect monogenic causes of early stroke, allowing individualized follow-up and opening new possibilities for potential treatment.

Genetic variants in BDNF (rs6265 and rs11030119) and stroke susceptibility: a case-control analysis in South India

Background Stroke occurs when the blood supply to part of the cerebral cortex is blocked, depriving it of oxygen and glucose, leading to cell death. It is a multifactorial disorder influenced by genetic, vascular, and environmental factors. Aim This study investigated the association between two polymorphisms of the brain-derived neurotrophic factor (BDNF) gene, rs6265 and rs11030119, and stroke risk in a South Indian population. Subjects and Methods The study included 163 stroke cases and 160 healthy controls. Genomic DNA was extracted, and genotyping of rs6265 and rs11030119 polymorphisms was done using ARMS-PCR. Allelic and genotype frequencies were calculated, and odds ratios (OR) with 95% confidence intervals (CI) were determined using SPSS version 21.0. Results The rs6265 polymorphism was significantly associated with stroke risk, with the GG genotype more frequent in controls (OR 1.79, 95% CI 1.05–1.76, p = 0.01). The rs11030119 polymorphism showed a positive association, with the AA genotype more prevalent in cases (OR 2.70, 95% CI 1.34–5.44, p = 0.003). Conclusion This study suggests an association between BDNF polymorphisms (rs6265, rs11030119) and stroke risk in a South Indian population. Further research in larger populations is necessary to confirm these findings and explore the mechanisms involved.

Contrasting Patterns of Population Genomic Structure Between Broadcast‐Spawning and Brooding Corals in Southeast Asia

ABSTRACTAimAs climate change increasingly threatens the world's coral reefs, enhancing their resilience by improving population connectivity for key reef species is crucial for ensuring their persistence. Here, we evaluate the population genomic structure of two common coral species, Pocillopora acuta and Porites sp., chosen due to their divergent life histories. Thousands of single‐nucleotide polymorphisms (SNPs) were sequenced and analysed to infer regional connectivity patterns in Southeast Asia, a region that harbours a tremendous diversity of marine life.LocationCoasts of the Malay Peninsula and northern Borneo, covering ~1 million km2.MethodNextRAD genotyping‐by‐sequencing of 185 Porites sp. and 221 Pocillopora acuta colonies. Libraries were prepared and sequenced on Illumina NovaSeq 6000. Genotyping involved initial quality controls, allele frequency filtering and checks for contamination. Genetic structure was assessed with Bayesian clustering, and relationships between genetic variation and environmental factors were studied through redundancy analysis. Contemporary gene flow was estimated using BayesAss.ResultsWe observed panmixia among the broadcasting Porites sp. populations, while for the brooding Pocillopora acuta, the Malay Peninsula acts a strong barrier to dispersal between the Malacca Strait and the southern South China Sea. Moreover, its genomic structure seems to follow current marine ecoregion delineation. By analysing contemporary migrant movement, we can prioritise reef localities for conservation. In particular, localities at the Andaman Coral Coast are contemporarily isolated from the other localities, and Tioman is identified as a major larval source for both species.Main ConclusionOur analyses highlight contrasting population differentiation patterns between the two species that can be explained by the disparity in their reproductive strategies. These findings are important for biodiversity managers in Southeast Asia; incorporation of regional connectivity considerations into conservation planning can help safeguard ecosystem resilience and persistence.

Multimodal AI/ML for discovering novel biomarkers and predicting disease using multi-omics profiles of patients with cardiovascular diseases

Cardiovascular diseases (CVDs) are complex, multifactorial conditions that require personalized assessment and treatment. Advancements in multi-omics technologies, namely RNA sequencing and whole-genome sequencing, have provided translational researchers with a comprehensive view of the human genome. The efficient synthesis and analysis of this data through integrated approach that characterizes genetic variants alongside expression patterns linked to emerging phenotypes, can reveal novel biomarkers and enable the segmentation of patient populations based on personalized risk factors. In this study, we present a cutting-edge methodology rooted in the integration of traditional bioinformatics, classical statistics, and multimodal machine learning techniques. Our approach has the potential to uncover the intricate mechanisms underlying CVD, enabling patient-specific risk and response profiling. We sourced transcriptomic expression data and single nucleotide polymorphisms (SNPs) from both CVD patients and healthy controls. By integrating these multi-omics datasets with clinical demographic information, we generated patient-specific profiles. Utilizing a robust feature selection approach, we identified a signature of 27 transcriptomic features and SNPs that are effective predictors of CVD. Differential expression analysis, combined with minimum redundancy maximum relevance feature selection, highlighted biomarkers that explain the disease phenotype. This approach prioritizes both biological relevance and efficiency in machine learning. We employed Combination Annotation Dependent Depletion scores and allele frequencies to identify variants with pathogenic characteristics in CVD patients. Classification models trained on this signature demonstrated high-accuracy predictions for CVD. The best performing of these models was an XGBoost classifier optimized via Bayesian hyperparameter tuning, which was able to correctly classify all patients in our test dataset. Using SHapley Additive exPlanations, we created risk assessments for patients, offering further contextualization of these predictions in a clinical setting. Across the cohort, RPL36AP37 and HBA1 were scored as the most important biomarkers for predicting CVDs. A comprehensive literature review revealed that a substantial portion of the diagnostic biomarkers identified have previously been associated with CVD. The framework we propose in this study is unbiased and generalizable to other diseases and disorders.

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

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

Population Genetic Dissection of HLA-DPB1 Amino Acid Polymorphism to Infer Selection

Although allele frequency data for most HLA loci provide strong evidence for balancing selection at the allele level, the DPB1 locus is a notable exception, with allele frequencies compatible with neutral evolution (genetic drift) or directional selection in most populations. This discrepancy is especially interesting as evidence for balancing selection has been seen at the nucleotide and amino acid (AA) sequence levels for DPB1. We describe methods used to examine the global distribution of DPB1 alleles and their constituent AA sequences. These methods allow investigation of the influence of natural selection in shaping DPβ diversity in a hierarchical fashion for DPB1 alleles, all polymorphic DPB1 exon 2-encoded AA positions, as well as all pairs and trios of these AA positions. In addition, we describe how asymmetric linkage disequilibrium for all DPB1 exon 2-encoded AA pairs can be used to complement other methods. Application of these methods provides strong evidence for the operation of balancing selection on AA positions 56, 85–87, 36, 55 and 84 (listed in decreasing order of the strength of selection), but no evidence for balancing selection on DPB1 alleles.