Genetically Research Articles

Identification of genetic risk variants for Type-2 Diabetes mellitus in Pakistani Pashtun population: A case-control association study

Background and Objective: Pakistan, a South Asian developing country, is experiencing a rapid increase in number of diabetes cases. High prevalence ratio of diabetes in Pakistani population and lack of genetic research studies prompted us to design this study. This present study investigated Pakistani Pashtun population for (known and novel SNPs) and its possible correlation with Type-2 Diabetes Mellitus (T2DM). Methods: This two stage (discovery & validation stage), case-control association study included one thousand individuals (Patients with T2DM=500 & controls=500) from eight districts of Khyber Pakhtunkhwa Pakistan. The study duration/period was from March 2018 to January 2020. In the first stage (the discovery stage) the target population was screened for known and novel T2DM-associated genetic markers. In the validation stage, identified variants were confirmed for T2DM association using MassARRAY genotyping and association analysis. Results: Exome sequencing detected eleven known and four novel/new genetic markers in the study population. Novel variants were preferred over the known for follow-up analysis/validation. Among the identified variants strong associations were confirmed for the following variants; rs1781133/ANKRD65 (OR=2.10, 95%Cl=1.06–3.08, P=0.003) rs2274791/TTLL10 (OR=1.97, 95%Cl=1.36-2.62, P=0.025), rs71628928/RNF223 (OR=1.82, 95%Cl=0.97-1.92, P=0.041), and rs609805/SCNN1D (OR=2.21, 95%Cl=1.92-3.09, P=0.001) with T2DM; other reported variants showed no noticeable association (having P>0.05) with T2DM. Conclusion: This study reports new genetic risk variants for T2DM in Pashtun population providing valuable insights into the genetic basis of T2DM in this group. doi: https://doi.org/10.12669/pjms.40.10.10292 How to cite this: Jan A, Mothana RA, Kaimori JY, Muhammad T, Khan M, Ali SS, et al. Identification of genetic risk variants for Type-2 Diabetes mellitus in Pakistani Pashtun population: A case-control association study. Pak J Med Sci. 2024;40(10):2336-2343. doi: https://doi.org/10.12669/pjms.40.10.10292 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data

ObjectivesExperimental and genetic studies suggest that fibroblast growth factor 21 (FGF21) modulates macronutrient and alcohol preferences, but evidence of such regulation in humans remains scarce. To address this gap in translation, we aimed to map the relationships between plasma FGF21 levels, FGF21 genetic variation and habitual macronutrient intake in a large human population. MethodsWe fine-mapped and performed colocalization of the FGF21 genetic region in GWAS summary statistics of plasma FGF21 levels and macronutrient intake. UK Biobank data were used to investigate the associations between FGF21 genetic variants, plasma FGF21 protein levels, and macronutrient intake (including alcohol) assessed with repeated 24-hour recalls. One- and two-sample mendelian randomization were performed to estimate the effects of plasma FGF21 on macronutrient intake. ResultsWe show that the main macronutrient-associated variant rs838133 and the FGF21 cis-pQTL rs838131, both in the FGF21 gene, are distinct genetic signals. Effect directions also suggest that the influence of FGF21 variation on macronutrient intake appear more complex than by direct mediation through plasma FGF21. Only when considering this complexity at FGF21, is plasma FGF21 estimated to reduce alcohol and increase protein and fat intake using mendelian randomization. Importantly, plasma FGF21 levels also appear markedly elevated by primarily high alcohol and low protein intake. ConclusionsThese findings support the feedback diet-regulatory mechanism of FGF21 in humans, but highlights the need for mechanistic characterization of the complex FGF21 genetic region.

The Effects of VEGF-A and GSTM1/GSTT1 Variants in the Susceptibility to the Chronic Rhinosinusitis with Nasal Polyposis: A Pilot Genetic Study.

Nasal polyps (NPs) are usually part of chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the exact etiology of CRSwNP is still unknown. In addition, the suggested etiological causes are infection, allergy, and immunological disorders, among others, such as genetic predisposition. Moreover, it is also suggested that oxygen-free radicals play a vital role in the pathogenesis of nasal polyposis, and inflammatory cells produce free radicals during phagocytosis, which is the primary source of ROS, controlled by the glutathione S-transferase (GST) system. Although, vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, it is closely interwoven with the mobilization of inflammatory cells. This pilot study evaluated the association between genetic variant VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphism in susceptibility to CRSwNP. A case-control study was conducted with 61 individuals diagnosed with CRSwNP and 100 healthy subjects. VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphisms were genotyped by RFLP-PCR and SYBR Green real-time PCR, respectively. Individuals with allergic rhinitis carriers with AC genotype (rs28357093) presented a 4-fold increased risk to CRSwNP (OR = 4.20, 95% CI = 1.31 to 13.50; p = 0.015). This evidence shows that the increased vascular permeability probably causes an inflamed nasal area leading to extensive edema and polyp growth. On the other hand, no association was verified for each genetic variant by inheritance models. Interestingly, the GSTT1 present genotype showed a protective effect on CRSwNP. In conclusion, additional studies that have larger groups in different geographic localizations may be useful to verify and assess the association between genetic variants and CRSwNP.

Clinical study on the utility of allergy tests to detect IgE-mediated anaphylaxis after diclofenac etalhyaluronate administration.

This study was conducted to investigate factors involved in anaphylaxis related to diclofenac etalhyaluronate (DEH) [product name: Joyclu® (JCL)] (containing DEH and macrogol 400), which is used to treat patients with osteoarthritis. Patients with osteoarthritis were divided into two groups that had (experienced patients) or had not experienced anaphylactic symptoms after JCL administration (non-experienced patients). Five tests performed to assess factors related to anaphylaxis consisted of a skin prick test (SPT) as the primary endpoint and the other tests including basophil activation test, allergen-specific IgE (sIgE) tests using enzyme-linked immunosorbent assay or immunochromatographic kits, and genetic study were secondary endpoints. The SPT showed 4 (wheal)/7 (erythema) of 15 experienced patients and 0/3 of 19 non-experienced patients were positive for any of the test reagents containing DEH. The basophil activation test showed two experienced patients were positive for test reagents containing DEH. DEH- and diclofenac-sIgE were detected in 3 and 1 of 12 experienced patients, respectively. No clear results were shown in the other tests. DEH may be the main factor involved in the development of anaphylaxis. The SPT was more sensitive than the basophil activation and allergen-sIgE tests for identifying factors associated with anaphylaxis.

Single nucleotide polymorphism (SNP) analysis reveals ancestry and genetic diversity of cultivated and wild grapevines in Croatia

BackgroundCroatia is a geographically small country with a remarkable diversity of cultivated and spontaneous grapevines. Local germplasm has been characterised by microsatellite markers, but a detailed analysis based on single nucleotide polymorphisms (SNPs) is still lacking. Here we characterize the genetic diversity of 149 accessions from three germplasm repositories and four natural sites using 516,101 SNPs to identify complete parent-offspring trios and their relations with spontaneous populations, offering a proof-of-concept for the use of reduced-representation genome sequencing in population genetics and genome-wide association studies (GWAS).ResultsPrincipal component analysis revealed a clear discontinuity between cultivated (V. vinifera subsp. sativa) and spontaneous grapevines, supporting the notion that the latter represent local populations of the wild progenitor (V. vinifera subsp. sylvestris). ADMIXTURE identified three ancestry components. Two sativa components are alternatively predominant in cultivars grown either in northern Adriatic Croatia and Continental Croatia or in Dalmatia (i.e. central and southern Adriatic Croatia). A sylvestris component, which is predominant in accessions from spontaneous populations, is a minor ancestry component in cultivated accessions. TREEMIX provided evidence of unidirectional migration from the vineyards to natural sites, suggesting that gene flow has gone preferentially from the introduced domesticated germplasm into local wild populations rather than vice versa. Identity-by-descent analysis indicated an extensive kinship network, including 14 complete parent-offspring trios, involving only cultivated accessions, six full-sibling relationships and invalidated a presumed pedigree of one of the most important varieties in Croatia, ‘Plavac Mali’. Despite this strong population structure, significant association was found between 143 SNPs and berry skin colour and between 2 SNPs and leaf hairiness, across two previously known genomic regions.ConclusionsThe clear genetic separation between Croatian cultivars and sylvestris ruled out the hypothesis that those cultivars originated from local domestication events. On the other hand, the evidence of a crop-to-wild gene flow signals the need for an urgent adoption of conservation strategies that preserve the residual genetic integrity of wild relatives. The use of this reduced-representation genome sequencing protocol in grapevine enables an accurate pedigree reconstruction and can be recommended for GWAS experiments.

A Diagnostic Guide for Orange Rust Disease in Sugarcane

Puccinia kuehnii is an important airborne fungal pathogen of sugarcane, causing orange rust disease. P. kuehnii has been present in the Asia–Oceania region for over a century. The first report of this pathogen in the Western Hemisphere was in 2007, when it appeared in Florida, U.S.A. The main objective of this diagnostic guide is to provide detailed information about symptoms and signs of sugarcane orange rust as well as taxonomy, geographic distribution, isolation, identification, and storage of P. kuehnii. We also highlight the management strategies used in recent years to control this devastating fungal disease. This diagnostic guide will help facilitate future research focusing on fungal isolation procedures, genetics, and population studies of this pathogen.

Genetic architecture of routinely acquired blood tests in a British South Asian cohort

Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.

Genetic Identification of Putative Hybrids Between Grey Wolf and Golden Jackal

We describe the results of genetic analysis of 11 phenotypically deviant individuals of grey wolf (Canis lupus Linnaeus, 1758) sensu lato collected in Voronezh State Nature Biosphere Reserve (Chernozem zone of European Russia) and Dagestan (Northern Caucasus, Russia) putatively identified morphologically as hybrids between grey wolf and golden jackal (Canis aureus Linnaeus, 1758). By means of maternally inherited mtDNA (sequences of cytochrome b gene fragment) and paternal lineage markers ZfY no F1 wolf-jackal hybrids were identified. As well, possibility of classification of the studied individuals to next generation hybrids from crosses between different wolf-jackal F1s. However, attribution of these animals to complex hybrids such as various backcrosses cannot be rejected. From the results of analysis by a set of autosomal microsatellite loci we putatively diagnosed a single F2 hybrid. As well, we obtained data that can be considered as traces of hybridization between wolf and jackal in southern regions of European Russa, albeit direct indications of introgression between these species not found. At the same time, the results of both genetic and craniological studies could be interpreted as indication to hybridization between wolves and domestic dogs on the same territories.

Multivariate Bayesian Analyses in Nursing Research: An Introductory Guide.

In the era of precision health, nursing research has increasingly focused on the analysis of large, multidimensional data sets containing multiple correlated phenotypes (e.g., symptoms). This presents challenges for statistical analyses, especially in genetic association studies. For example, the inclusion of multiple symptoms within a single model can raise concerns about multicollinearity, while individual SNP-symptom analyses may obscure complex relationships. As such, many traditional statistical approaches often fall short in providing a comprehensive understanding of the complexity inherent in many nursing-focused research questions. Multivariate Bayesian approaches offer the unique advantage of allowing researchers to ask questions that are not feasible with traditional approaches. Specifically, these methods support the simultaneous exploration of multiple phenotypes, accounting for the underlying correlational structure between variables, and allow for formal incorporation of existing knowledge into the statistical model. By doing so, they may provide a more realistic view of statistical relationships within a biological system, potentially uncovering new insights into well-established and undiscovered connections, such as the probabilities of association and direct versus indirect effects. This valuable information can help us better understand our phenotypes of interest, leading to more effective nurse-led intervention and prevention programs. To illustrate these concepts, this paper includes an application section covering two specific multivariate Bayesian analysis software programs, bnlearn and mvBIMBAM, with an emphasis on interpretation and extension to nursing research. To complement the paper, we provide access to a detailed online tutorial, including executable R code and a synthetic data set, so the concepts can be more easily extended to other research questions.

Unveiling Genetic Diversity Among Bacterial Isolates Using SCoT Markers.

This study aimed to unveil the genetic diversity among 47 bacterial isolates from various species using start codon targeted (SCoT) markers. Six SCoT primers yielded 219 reproducible bands, with 89.04% exhibiting polymorphism. The amplification process generated 28 to 50 fragments per primer, with an average of 36.50. Genetic diversity was quantified using polymorphic information content (PIC) values ranging from 0.11 to 0.14, with SCoT32 showing the highest PIC (0.14) and SCoT23 the lowest (0.11). The resolving power (RP) index, used to assess primer discriminatory power, varied significantly, with SCoT23 demonstrating the highest RP (6.00) and SCoT29 the lowest (4.51). Comparative analysis with conventional markers like M13 and (GTG)5 revealed that certain SCoT primers exhibited superior PIC values, which indicates enhanced utility for interspecies differentiation. The high discrimination level achieved by SCoT primers underscores their effectiveness in genetic differentiation and biodiversity assessment within bacterial populations. This research highlights SCoT markers as powerful tools for microbial genetic studies, which offers valuable insights into bacterial diversity and provides a robust methodological framework for future investigations aimed at elucidating genetic variation and improving species identification. The application of SCoT markers represents a significant advancement in molecular techniques for bacterial characterization and phylogenetic analysis, demonstrating their potential to enhance our understanding of microbial genetics and evolution.

Genetic association study of preterm birth and gestational age in a population-based case-control study in Peru.

Preterm birth (PTB) affects ∼15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. PTB cases delivered≥20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥37 weeks but <42 weeks). Multivariable regressions were used to identify genetic markers for PTB and GA (∼6 million SNPs), adjusting for maternal age and the first two genetic principal components. In silico functional analysis was conducted among top signals detected with an arbitrary P < 1.0×10-5. We sought to replicate genetic markers for PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. Mean GA was 30 ± 4 weeks in PTB cases (N = 933) and 39 ± 1 in the controls (N = 1,279). No associatiosn were identified at genome-wide level. Nominal PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Nominal GA variants were enriched in intronic regions and cancer pathways. Variants in WNT4 associated with GA in Europeans were replicated in our study. A genetic risk score was associated with a 2-day longer GA (P = 0.002) in our sample. This study identified various signals suggestively associated with PTB and GA in pregnant Peruvian women. None of these variants overlapped with signals previously identified in Europeans.

A discussion of pediatric therapy-related acute myeloid leukemia with a rare t(8;16) translocation

Abstract Introduction/Objective Secondary acute myeloid leukemia is a type of blood cancer that arises after a previous myeloid neoplasm or after exposure to chemotherapy. Certain genetic mutations and chromosomal abnormalities can occur as a result of said cytotoxic drug-related effects. Here, we discuss a case of secondary acute myeloid leukemia with a rare translocation following hemophagocytic lymphohistiocytosis Etoposide treatment in a 13-year-old female. After less than a year into her initial treatment, the patient presented to the emergency department with severe bone pain. A full hematologic workup was performed, including bone marrow biopsy, flow cytometry analysis, and subsequent genetic studies. A diagnosis of therapy-related acute myeloid leukemia was made. Genetic studies revealed a rare t(8;16) translocation which presents with a unique morphology and prognosis that will be discussed here. Methods/Case Report A 13-year-old female presented to the emergency department for evaluation of fever, myalgia, and swelling in her clavicle. The patient’s history was notable for hemophagocytic lymphohistiocytosis with subsequent Etoposide chemotherapy treatment which she received less than a year prior to her visit. CBC was notable for low white blood cell count, low hemoglobin, increased neutrophilic bands, and decreased lymphocytes. Given her past medical history and worsening pain without a clear reason, hematology was consulted. Results (if a Case Study enter NA) A blast count of 61.8% was reported via flow cytometry with the cells seen in the dim CD45+, moderate to bright side-scatter region, co-expressing CD4, CD14 (dim, heterogeneous), CD15, CD16 (dim), CD64, HLA-DR, and MPO. The bone marrow biopsy was described as hypercellular with the predominant cell type as blasts at 66.4%. Numerous hemophagocytic blasts were noted as well. Acute leukemia next generation sequencing panel revealed a t(8;16)(p11;p13.3) KATA6A::CREBBP fusion without other abnormalities in the evaluated genes. This workup as a whole rendered the diagnosis of acute myeloid leukemia with KAT6A::CREBBP. Conclusion Diagnosing acute myeloid leukemia with KATA6A::CREBBP is important for prognostic factors. Knowing the patient’s history regarding her prior chemotherapy with Etoposide is also imperative for distinguishing a de novo presentation of this rare subtype, versus a therapy-related myeloid neoplasm. The patient was started on chemotherapy for her acute myeloid leukemia shortly thereafter the diagnosis.

Cardiovascular Disease Risk in the Obese Population in Kuwait: A Systematic Review and Meta-Analysis.

The increasing prevalence of obesity and associated cardiovascular diseases (CVDs) in Kuwait requires a comprehensive analysis of its contributing factors and health outcomes. This systematic review and meta-analysis aimed to synthesize the current evidence on the relationship between obesity and CVDs and identify the main factors driving obesity in the Kuwaiti population. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, multiple databases were systematically searched, identifying 980 articles. After removing duplicates and screening the articles against the inclusion criteria (observational or intervention studies published from 2001 to 2024 in English, conducted in Kuwait or on Kuwaitis, examining obesity (body mass index or validated measures) and CVDs (coronary artery disease, stroke, heart attack, hypertension, dyslipidemia, diabetes), 44 published studies from 2001 to 2024 were included in the final analysis. The studies varied widely in design and population, complicating the estimation of the total number of participants. The pooled prevalence of overweight patients was 36% (95% CI: 25-47) with high heterogeneity (I2=99.86%) and a statistically non-significant difference (p>0.01). Likewise, the pooled prevalence of overweight patients was 31% (95% CI: 23-40,I2=99.03%), with a statistically non-significant difference (p>0.01). The key factors contributing to obesity in Kuwait include a sedentary lifestyle, unhealthy diet, poor sleep quality, stress, genetic predisposition, metabolic disorders, environmental factors, and cultural factors. Sedentary behavior and unhealthy diets, exacerbated by rapid urbanization and economic growth, were prominent contributors. Genetic studies have identified specific genetic variants associated with obesity. Stress and poor sleep quality were significant factors, particularly in urban environments. A strong association was found between obesity and various CVD risk factors, including hypertension, dyslipidemia, and diabetes mellitus, with pooled population attributable risk estimates of 15%-18%, 13%-15%, and 10%, respectively. These findings underscore the multifaceted nature of obesity in Kuwait, which is influenced by lifestyle, dietary habits, genetic factors, and socioeconomic changes. Age- and gender-specific analyses revealed higher obesity rates in adults aged 40-60 years and stronger associations with CVD in females. The consistent link between obesity and CVD risk factors highlights the urgent need for targeted public health interventions. Obesity contributes significantly to the CVD burden in Kuwait, driven by a combination of lifestyle, genetic, and environmental factors. Comprehensive strategies addressing these determinants are essential to mitigate the obesity epidemic and its associated health risks in the Kuwaiti population.

Neonatal Hemochromatosis Secondary to an Inborn Error of Metabolism (Mitochondrial Disorder): Post- mortem Diagnosis in the Fetus of a Young Primipara

Abstract Introduction/Objective Neonatal hemochromatosis (NH), an extremely rare congenital phenotype of acute hepatic failure with hepatic and extrahepatic siderosis, is primarily (98%) caused by gestational alloimmune liver disease (GALD) and, rarely (2%), by infection, metabolic disorders, bile acid defects, and mitochondrial hepatopathy. This report presents an extremely rare case of NH caused by an inborn error of metabolism (suspected mitochondrial dysfunction). This low-birth-weight female was born with acute liver failure, metabolic acidosis, multisystem failure, and progressive lactate acidosis, and expired on day 7. On autopsy, liver was less than 50% of normal size and without nodularity. Microscopic architecture was preserved with erythropoiesis, canalicular bile plugs, microvesicular steatosis (oil red O stain) and abundant coarsely granular siderosis (iron stain). GALD was unlikely because of the absence of the typical hepatocytic injury, fibrosis or biliary destruction, and the negative immunohistochemistry for MAC (C5b-C9). Extrahepatic siderosis was demonstrated in thyroid follicles, thymic Hassall corpuscles, myocardium, and adenohypophysis. Sanger sequencing and deletion testing of mitochondrial genome on a maternal buccal biopsy identified a homoplasmic variant (m.15482 T&amp;gt;C p.(S246P) in maternal MT-CYB gene but without molecular diagnosis of a mitochondrial DNA disorder. Infant plasma had increased C6DC, C5, C12-OH acylcarnitine, alanine, and proline. Urine contained elevated organic acids (lactate/pyruvate, 2-ketoacids, 3-methylglutarate, 3-methylglutaconate), concerning acute mitochondrial respiratory chain dysfunction. Methods/Case Report: Case Study Results (if a Case Study enter NA) NA Conclusion Diagnosis of NH warrants exclusion of the most common etiology, GALD. Mitochondrial genetic mutations are the most difficult to diagnosis because of heterogeneity and typically undiagnosed maternal defects. This is the first report of NH with a homoplasmic maternal variant of uncertain significance. Neonatal lactic acidosis is the strongest clinical clue for mitochondrial dysfunction and should trigger phenotyping, maternal mitochondrial genetic variants (mtDNA, nuDNA), functional, biochemical, and genetic studies.

CELL-INTRINSIC METABOLIC PHENOTYPES IDENTIfiED IN GLIOBLASTOMA PATIENTS USING MASS SPECTROMETRY IMAGING OF 13C-LABELED GLUCOSE METABOLISM

Abstract AIMS Glioblastoma (GB) is an inherently heterogenous and invasive primary brain tumour. Genetic and transcriptomic studies have attempted to classify GB into subtypes that can identify therapeutic vulnerabilities and predict survival. An outstanding question and technical challenge is to visualise the metabolism of a tumour within its native microenvironment and understand to what extent its metabolism is driven by the microenvironment. METHOD Patients with GB tumours were infused with [U-13C]glucose and intra-operative multi-regional tumour samples were rapidly snap frozen for metabolic tracing analysis using mass spectrometry imaging (MSI). Tissue microenvironment was assessed using multiplexing of antibodies on immunocytochemistry (IMC) of parallel sections. Isotope tracing in human derived neurospheres and patient derived xenografts were used to confirm the presence of metabolic phenotypes detected in the human samples and to test susceptibility of each phenotype to a panel of drugs targeting cellular metabolism. RESULTS Three metabolic signatures were identified in patient GB tumours: glycolytic, oxidative and a mixed glycolytic/oxidative phenotype. The phenotypes did not correlate with microenvironmental features, including proliferation rate, immune cell infiltration, and vascularisation. The phenotypes were retained when patient derived cells were grown in vitro, or as orthotopically implanted xenografts, and were robust to changes in oxygen concentration, demonstrating their cell intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes are large enough to be detected using clinically applicable metabolic imaging techniques. The phenotypes also demonstrate differential drug sensitivities. CONCLUSION This is the first report to demonstrate high resolution imaging of metabolic fluxes in a human tumour in vivo. In conjunction with studies on patient-derived neurospheres and orthotopically implanted xenografts we have demonstrated the presence of different metabolic phenotypes within GB that are tumour cell intrinsic and largely independent of the tumour microenvironment. These can be imaged clinically and used to stratify patients for personalised therapy.

Common roots of Riza Fakhretdin and the Service Tatars Baishevs in the context of Genetic Genealogy

The publication presents a comparative analysis of the results of genetic studies and information from the funds of the “Local Order” (f. 1209) and “Landrat Books and Census Records” (f. 350) of the Russian State Archive of Ancient Acts concerning the genealogy of the famous scientist-educator, historian, theologian and public figure Rizaetdin Fakhretdin. As a result of the study, the plausibility of the family legends of R. Fakhretdin about the origin of his ancestors from the Shirdan village of Sviyazhsk district, was proven, their common origin with the famous service Service Tatar family of the Baishevs was shown. For citation: Vladimirov O.O. Common roots of Riza Fakhretdin and the Service Tatars Baishevs in the context of Genetic Genealogy. From History and Culture of Peoples of the Middle Volga Region. 2024, vol.14, no.3, pp.146–153. https://doi.org/10.22378/2410-0765.2024-14-3.146-153 (In Russian)

Genetic overlap between idiopathic scoliosis and schizophrenia in the general population.

Adolescent idiopathic scoliosis (AIS) and schizophrenia (SCZ) are two distinct conditions with poorly understood aetiologies that both emerge in otherwise healthy young adolescents. One rare genetic condition associated with both phenotypic outcomes is the 22q11.2 deletion (22q11DS). This microdeletion, encompassing 47 genes, occurs in approximately 1 in 2,148 live births and confers a 20-fold higher risk for both AIS and schizophrenia compared to the general population. In the general population (non-22q11DS carriers), AIS and SCZ have also been reported to be related and genetic studies suggest the involvement of genetic variants implicated in the central nervous functioning. In this study, our objective was to further investigate genetic overlaps between these conditions in the general population. Specifically, we aimed to explore the role of genes within the 22q11.2 region, not only in terms of common variants but also their potential impact on gene networks and biopathways. We used summary statistics from three genome-wide association studies (GWAS): two focused on AIS (n = 11,210), and one on schizophrenia (n = 36,989). To explore potential overlaps between the two conditions, we conducted a comparative analysis on the significance-based ranked single nucleotide polymorphisms (SNPs) that are associated with both AIS and SCZ. Next, we employed in silico analyses to assess gene-networks enrichment for the most significant SNPs and investigate the contribution of genes within the 22q11.2 region. Post-hoc analysis was conducted to explore the biological pathways correlated with SNPs significantly associated with both AIS and SCZ. The in silico analyses revealed a significant (adjusted-p < 0.05) genetic overlap between SCZ and both AIS cohorts. The top 3% of the most significant SNPs associated with both conditions exhibited a distinct enrichment cluster which is unlikely to be a result of chance (p < 3e-04). The gene-networks analyses showed a significant overlap of 26-41% with the ones involving genes in the 22q11DS region. However, there was no overlap between SNPs in this region and the most significant SNPs identified in the GWAS. This study revealed compelling evidence that beyond the shared association with 22q11DS as a rare genetic variant, AIS and SCZ exhibit common genetic risk variants and an overlap of important genes. The gene networks enriched by the most significant SNPs for both conditions also intersect with the ones involving genes in the 22q11DS region. However, SNPs within this region were not overrepresented among the most significant SNPs from GWAS for both conditions. Notably, gene networks linked to the risk for both conditions suggest an involvement of biopathways related to cellular signaling and neuronal development.

Comparative Genetic Study of Local and Introduced Cattle Breeds of Khizi District of Azerbaijan Republic

A comparative genetic study of local and introduced breeds of cattle in the farms of the Khizi district was carried out. Cattle of various breeds are kept on the territory of the region at enterprises of legal entities and individuals, in farms belonging to individual owners. Introduced breeds of cattle, beef and dairy cattle make up 0.0029% of the total livestock. Simmental (25%), Holstein-Frisian (27%), Brown Swiss (12%) and Aberdeen-Angus (7%) breeds are derived from introduced beef and dairy cattle. For a comparative study of the genomes of local and introduced breeds of cattle, blood samples were taken, DNA was obtained and prepared for further analysis.

A fascination with tailless mice: a scientific historical review of studies of the T/t complex.

The T/t complex of the mouse attracted many of the major figures of mouse genetics to perform genetic, cytogenetic, physiological, biochemical and molecular biological studies of it. These studies started with the discovery of short tailed mutants (Ts) and recessive lethal developmental mutations (ts) which mapped to the same "locus" in the early 1920s in France. However, due to the non-receptivity of French scientists to genetics, they continued to be studied in mostly Anglophone countries to be joined by a wider international community in the 1970s. These discoveries led to developmental studies of the lethal mutants which provided the origin of mammalian developmental genetics. The fascinating property of transmission ratio distortion (non-50/50 segregation of alleles in offspring of males) elicited tremendous interest. There were false leads (that the region consisted of unusual DNA, that the alleles controlled cell surface antigens on embryonic cells and spermatozoa) and exciting discoveries. This historical review provides a review of this extensive area of research and some of the individuals involved in it.

Characterization of Nuclear Mitochondrial Insertions in Canine Genome Assemblies

Background: The presence of mitochondrial sequences in the nuclear genome (Numts) confounds analyses of mitochondrial sequence variation, and is a potential source of false positives in disease studies. To improve the analysis of mitochondrial variation in canines, we completed a systematic assessment of Numt content across genome assemblies, canine populations and the carnivore lineage. Results: Centering our analysis on the UU_Cfam_GSD_1.0/canFam4/Mischka assembly, a commonly used reference in dog genetic variation studies, we found a total of 321 Numts located throughout the nuclear genome and encompassing the entire sequence of the mitochondria. A comparison with 14 canine genome assemblies identified 63 Numts with presence–absence dimorphism among dogs, wolves, and a coyote. Furthermore, a subset of Numts were maintained across carnivore evolutionary time (arctic fox, polar bear, cat), with eight sequences likely more than 10 million years old, and shared with the domestic cat. On a population level, using structural variant data from the Dog10K Consortium for 1879 dogs and wolves, we identified 11 Numts that are absent in at least one sample, as well as 53 Numts that are absent from the Mischka assembly. Conclusions: We highlight scenarios where the presence of Numts is a potentially confounding factor and provide an annotation of these sequences in canine genome assemblies. This resource will aid the identification and interpretation of polymorphisms in both somatic and germline mitochondrial studies in canines.