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In terms of prevalence, 11β-hydroxylase deficiency (11β-OHD), a common form of congenital adrenal hyperplasia, closely follows 21-hydroxylase deficiency. 11β-OHD has been attributed to diminished enzymatic activity owing to CYP11B1 gene variants, mainly encompassing single nucleotide variations and insertions-deletions. The involvement of chimeric CYP11B2/CYP11B1 genes in 11β-OHD has rarely been reported. We conducted a genetic investigation on a male infant with generalized pigmentation and abnormal steroid hormone levels. Whole-exome sequencing revealed a heterozygous variant in CYP11B1 inherited from the mother (NM_000497.4: c.1391_1393dup [p.Leu464dup]). Long-range polymerase chain reaction revealed an additional allele, a chimeric CYP11B2/CYP11B1 gene, inherited from the father. The current case report highlights the need to consider the occurrence of gene fusion variants in the diagnosis of neonatal or early infantile 11β-OHD. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the allele frequencies of the human platelet antigens (HPA) HPA-1-29w system in Jiangsu (China) and establish the platelet apheresis registry in blood donors. Methods: HPA genotyping was performed using the MassARRAY iPLEX® platform. Allele and genotype frequencies were estimated by direct counting and tested for Hardy-Weinberg equilibrium. The transfusion mismatch probability was calculated for every HPA specificity. Results: The HPA allele frequencies in the Jiangsu Han population of HPA-1b, -2b, -3b, -4b, -5b, -6b, -11b, -15b, and -21b were 0.0055, 0.0530, 0.4116, 0.0015, 0.0155, 0.0162, 0.0003, 0.4683, and 0.0070, respectively, in which a heterozygote of HPA-11a/b was first detected in China. Only allele a was detected for HPA-7-10w,-12-14w,-16-20w, and -22-29w quasi-systems. The highest mismatch rate of HPA genes in 1,640 platelet donors was the HPA-15 system, followed by the HPA-3 system with a rate of 37.4% and 36.71%, respectively. Conclusion: China's largest-scale platelet registry of HPA-1-29w has been explored. The MassARRAY platform may help found the platelet apheresis registry which would be useful to provide matching platelets and lead to a more accurate, effective, and safe transfusion for patients with platelet therapy. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes (streptocoque bêta-hémolytique du groupe A, SGA) est un pathogène strictement humain, de répartition mondiale. Le SGA est responsable d'un large éventail de manifestations cliniques allant des infections non invasives, les plus nombreuses, aux infections invasives, plus rares mais pouvant être fatales, tels la fasciite nécrosante et le syndrome de choc toxique streptococcique (SCTS). Dans la population pédiatrique, les infections à SGA se manifestent principalement par des angines. Les infections invasives, moins fréquentes que chez l'adulte, surviennent fréquemment sous la forme d'érysipèles, de pleuro-pneumopathies pouvant compliquer des infections virales respiratoires et d'ostéomyélites ou ostéoarthrites. Une recrudescence des infections à SGA a été décrite depuis les années 1980, survenant sous forme de bouffées épidémiques, la dernière datant de l'automne 2022, à la faveur de différents clones. La diversité des manifestations cliniques est associée à de nombreux facteurs de virulence parmi lesquels la protéine M, les streptolysines et les toxines superantigéniques. La protéine M, codée par le gène emm , est immunogène et présente une grande diversité antigénique. Parmi les plus de 200 génotypes emm décrits, les génotypes emm1 et emm3 sont plus fréquemment associés aux formes les plus sévères. En outre, le SGA possède jusqu'à 11 gènes distincts codant des toxines superantigéniques pouvant être responsables d'une stimulation immunitaire massive conduisant au SCTS. Le SGA est constamment sensible aux bêta-lactamines, considérées comme le traitement de choix des infections à SGA. La surveillance continue des infections à SGA reste essentielle afin d'ajuster les mesures thérapeutiques et prophylactiques et d'évaluer l'impact potentiel des futurs vaccins. Streptococcus pyogenes (or group A Streptococcus , GAS) is a human-specific pathogen, with a worldwide distribution, responsible for a wide range of diseases, ranging from superficial to life-threatening invasive infections, including necrotizing fasciitis and streptococcal toxic shock syndrome (STSS). In the paediatric population, GAS infections mainly occur as pharyngitis whereas invasive infections are less frequent than in adults and frequently manifesting as erysipelas, pleural and pulmonary infections that may complicate respiratory viral infections, and osteomyelitis or osteoarthritis. A resurgence of GAS infections has been described since the 1980s, emerging as outbreaks, most recently in autumn 2022, as a result of different clones. The diversity of clinical manifestations is associated with numerous virulence factors, including the M protein, streptolysins and superantigenic toxins. The M protein, encoded by the emm gene, is immunogenic and has a wide antigenic diversity. Among the over 200 emm genotypes described, emm1 and emm3 are more frequently associated with the most severe cases. GAS encodes up to 11 distinct genes encoding superantigenic toxins that may be responsible for massive immune stimulation leading to STSS. GAS is always susceptible to beta-lactam antibiotics, considered to be the gold standard to treat GAS infections. Ongoing monitoring of GAS infections remains essential in order to adjust therapeutic and prophylactic measures and to assess the potential impact of future vaccines. [ABSTRACT FROM AUTHOR]

The NGM Detect™ PCR Amplification Kit was designed particularly for genotyping degraded casework samples. This study aimed to validate the half‐volume amplification of the kit and to present its successful long‐term application. The validation was performed in accordance to the corresponding guidelines of the Scientific Working Group on DNA analysis methods and the European Network of Forensic Science Institutes. For validation parameters, such as sensitivity, reproducibility, and repeatability, polymerase chain reactions (PCR) were set up both manually and robotically, applying 29 cycles. For PCRs with sub‐optimal DNA input (≤0.5 ng) the cycle numbers were increased to 31. Regardless of the PCR preparation method, the optimal 0.5 ng DNA input produced optimal allelic peak heights with no allelic dropout. The first alleles that failed to amplify started to appear at the level of 0.0375 ng input DNA, although the manually prepared PCRs produced fewer missing alleles. In this case, the raised cycle number produced 1.9% and 4.4% of dropout for manually and for robotically set up PCRs, respectively. In the case of 84 degraded casework samples, PCRs were prepared only by hand. The kit was able to provide informative profiles for 78.57%, 70.37%, and 69.77% for lowly, moderately, and highly degraded samples, respectively. Allelic dropouts were 26.05%, 44.88%, and 51.23% for the same groups. According to our results, we strongly recommend using the NGM Detect™ Kit in half‐volume PCR system and encourage the usage of the kit in the particular cases when other kits fail to produce a complete DNA profile. [ABSTRACT FROM AUTHOR]

DNA typing of latent fingerprints is highly desirable to increase chances of individualization. We recovered DNA from Cyanoacrylate (CA) fumed fingerprints and used both GlobalFiler™ and ForenSeq™ DNA Signature Prep kits for DNA typing. For GlobalFiler™, samples were processed using a protocol modified for Low Template (LT)‐DNA samples (half‐volume reactions, 30 cycles) while for ForenSeq™ DNA Signature Prep, samples were processed using a standard protocol and fluorometer‐based library quantitation. We evaluated genotyping success and quality of profiles in terms of completeness, Peak Height Ratio/Allele Coverage Ratio, presence of PCR artifacts and drop‐in alleles. With GlobalFiler™, average autosomal STR (aSTR) profile completeness was 44.4% with 2–20 pg, 54.3% with 22–60 pg, and 95% with 64–250 pg DNA input. CODIS uploadable profiles were obtained in 2/10, 3/11, and 11/12 samples in these ranges. With ForenSeq™ DNA Signature Prep, average aSTR profile completeness was 19.7% with 1–20 pg and 45.2% with 22–47 pg but increased to 78.3% with 68–122 pg and 86.7% with 618–1000 pg DNA input. Uploadable profiles were obtained in 0/12, 4/11, 4/7, and 3/3 samples for these ranges. Results show very high sensitivity using both kits. Half‐volume reactions and 30 cycles had minimal negative effect on Globalfiler™ profile quality, providing support for wider use after validation experiments to routinely improve results from LT samples. A standard protocol for the ForenSeq™ DNA Signature Prep kit was also highly successful with LT DNA obtained from CA‐fumed fingerprints with additional information from isometric STR alleles and other markers. [ABSTRACT FROM AUTHOR]

ACTN3 R577X and ACE I/D polymorphisms are associated with endurance exercise ability. This case–control study explored the association of ACTN3 and ACE gene polymorphisms with elite pure endurance in Korean athletes, hypothesizing that individuals with both ACTN3 XX and ACE II genotypes would exhibit superior endurance. We recruited 934 elite athletes (713 males, 221 females) and selected 45 pure endurance athletes (36 males, 9 females) requiring "≥90% aerobic energy metabolism during sports events", in addition to 679 healthy non-athlete Koreans (361 males, 318 females) as controls. Genomic DNA was extracted and genotyped for ACTN3 R577X and ACE I/D polymorphisms. ACE ID (p = 0.090) and ACTN3 RX+XX (p = 0.029) genotype distributions were significantly different between the two groups. Complex ACTN3-ACE genotypes also exhibited significant differences (p = 0.014), with dominant complex genotypes positively affecting endurance (p = 0.039). The presence of RX+II or XX+II was associated with a 1.763-fold higher likelihood of possessing a superior endurance capacity than that seen in healthy controls (90% CI = 1.037–3.089). Our findings propose an association of combined ACTN3 RX+XX and ACE II genotypes with enhanced endurance performance in elite Korean athletes. While causality remains to be confirmed, our study highlights the potential of ACTN3-ACE polymorphisms in predicting elite endurance. [ABSTRACT FROM AUTHOR]

The polymorphism of HLA class II genes was studied in COVID-19 survivors and vaccinated people. Six allelic variants of DQA1, 10 of DQB1, and 11 of DRB1 were identified. The DQA1*05:01 allele predominated in vaccinated volunteers and the DQA1*02:01, *01:03, and DQB1*06:02-8 alleles predominated in convalescents. In the groups with DQA1*01:01, *05:01 and *06:01 alleles, a high proportion of individuals seropositive for SARS-CoV-2 S protein was found. In the group with DQA1*02:01 allele, 40% of volunteers were found to have IgM and a significantly lower quantity of IgG to N protein of coronavirus. Comparative analysis showed a statistically significant increase in IL-10 levels in carriers of the DQA1*01:01 allele, which may indicate the influence of this allele on cytokine production. Further study of the immune response indices and their association with HLA class II gene polymorphism will provide better understanding of the mechanisms of COVID-19 immunogenesis. [ABSTRACT FROM AUTHOR]

To investigate the association of attention‐deficit/hyperactivity disorder (ADHD) with the 48‐base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64–1.3). The p‐value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12–0.92) and p = 0.03. Because our study used TDT analysis, we meta‐analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80–1.2) and p = 0.8. To examine the association of 2R with inattentive ADHD, we meta‐analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57–1.1) and p = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation. [ABSTRACT FROM AUTHOR]

The Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) is a surrogate marker for symptom evaluation in chronic myeloproliferative neoplasms (MPNs). However, insufficient data are available regarding the relationship among the MPN-SAF TSS, JAK2 mutation allele burden, and thrombosis. In this retrospective analysis, we aimed to determine the genetic burdens, clinical features, and relationships with MPN-SAF TSS in MPN patients. One hundred thirty JAK2V617F-positive patients with MPNs were included in our study. We calculated the MPN-SAF TSS for all patients and compared it with their clinical characteristics. Patients with higher JAK2V617F mutation allele burden had higher MPN-SAF TSS values (p=0.008). Patients with thrombosis had higher MPN-SAF TSS than patients without thrombosis (p=0.003). The mean MPN-SAF TSS was higher in patients with primary myelofibrosis compared to those with polycythemia vera and essential thrombocythemia. Thrombosis was associated with increased symptom severity in several domains, including fatigue, abdominal discomfort, inactivity, night sweats, pruritus, weight loss, and early satiety. Additionally, an increase in JAK2 allele burden was observed with higher symptom scores. The MPNSAF TSS proved to be a reliable tool for assessing symptom burden in Turkish MPN patients. Furthermore, the significant association between thrombosis occurrence and symptom severity suggests that thrombotic events may contribute to symptom development. Notably, increasing JAK2 allele burden was correlated with more severe symptoms, highlighting its potential role in predicting disease burden. This study emphasizes the importance of symptom assessment in MPN patients and supports the incorporation of the MPN-SAF TSS in routine clinical practice to enhance patient care and management. [ABSTRACT FROM AUTHOR]

The resistance gene Lr34 conditions durable disease resistance to many biotrophic wheat pathogens and has been incorporated into many wheat cultivars throughout the world. Lr67 is a similar adult plant resistance gene that also conditions resistance to multiple wheat diseases. Both genes significantly reduce disease severity and work in an additive manner with other rust resistance genes. To determine the effect of Lr34 and Lr67 on Fusarium head blight (FHB), two doubled haploid populations, segregating for each of these genes, were developed in the Thatcher wheat background by crossing near‐isogenic lines. Progeny from these populations were tested in five Fusarium graminearum‐inoculated disease nurseries and assessed for FHB symptoms, using a visual rating index (VRI), and deoxynivalenol (DON) accumulation. Both Lr34 and Lr67 significantly reduced visual symptoms of FHB and DON overall, though those effects were not significant in all environments. The overall reduction in the group of progeny with the resistant allele compared to the group with the susceptible allele for VRI was 9.4% for Lr34 and 6.8% for Lr67, while for DON it was 16.4% for Lr34 and 14.9% for Lr67. These genes represent important tools for improving resistance to FHB and many other diseases in wheat. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate an association between polymorphisms of either the VEGF (vascular endothelial growth factor) gene (rs6921438) or the KDR (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the VEGF gene (rs6921438) or the KDR gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for KDR (rs1617640, rs2305948) and VEGF (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 KDR gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 VEGF gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438-VEGF compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm2 vs. 1.24 ± 0.5/0.1 mm2, respectively; p < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm2 vs. 1.14 ± 0.5/0.1 mm2, respectively; p < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 KDR gene was associated with a higher risk of DN, while the G allele of the rs6921438-VEGF conferred protection against DN in Slovenian T2DM subjects. [ABSTRACT FROM AUTHOR]

There are more than 260 million people of Slavic descent worldwide, who reside mainly in Eastern Europe but also represent a noticeable share of the population in the USA and Canada. Slavic populations, particularly Eastern Slavs and some Western Slavs, demonstrate a surprisingly high degree of genetic homogeneity, and, consequently, remarkable contribution of recurrent alleles associated with hereditary diseases. Along with pan-European pathogenic variants with clearly elevated occurrence in Slavic people (e.g., ATP7B c.3207C>A and PAH c.1222C>T), there are at least 52 pan-Slavic germ-line mutations (e.g., NBN c.657_661del and BRCA1 c.5266dupC) as well as several disease-predisposing alleles characteristic of the particular Slavic communities (e.g., Polish SDHD c.33C>A and Russian ARSB c.1562G>A variants). From a clinical standpoint, Slavs have some features of a huge founder population, thus providing a unique opportunity for efficient genetic studies. [ABSTRACT FROM AUTHOR]

The Hardy–Weinberg equilibrium (HWE) assumption is essential to many population genetics models. Multiple tests were developed to test its applicability in observed genotypes. Current methods are divided into exact tests applicable to small populations and a small number of alleles, and approximate goodness-of-fit tests. Existing tests cannot handle ambiguous typing in multi-allelic loci. We here present a novel exact test Unambiguous Multi Allelic Test (UMAT) not limited to the number of alleles and population size, based on a perturbative approach around the current observations. We show its accuracy in the detection of deviation from HWE. We then propose an additional model to handle ambiguous typing using either sampling into UMAT or a goodness-of-fit test test with a variance estimate taking ambiguity into account, named Asymptotic Statistical Test with Ambiguity (ASTA). We show the accuracy of ASTA and the possibility of detecting the source of deviation from HWE. We apply these tests to the HLA loci to reproduce multiple previously reported deviations from HWE, and a large number of new ones. [ABSTRACT FROM AUTHOR]

The long-term balancing selection acting on mating types or sex-determining genes is expected to lead to the accumulation of deleterious mutations in the tightly linked chromosomal segments that are locally ‘sheltered’ from purifying selection. However, the factors determining the extent of this accumulation are poorly understood. Here, we took advantage of variations in the intensity of balancing selection along a dominance hierarchy formed by alleles at the sporophytic self-incompatibility system of the Brassicaceae to compare the pace at which linked deleterious mutations accumulate among them. We first experimentally measured the phenotypic manifestation of the linked load at three different levels of the dominance hierarchy. We then sequenced and phased polymorphisms in the chromosomal regions linked to 126 distinct copies of S-alleles in two populations of Arabidopsis halleri and three populations of Arabidopsis lyrata. We find that linkage to the S-locus locally distorts phylogenies over about 10–30 kb along the chromosome. The more intense balancing selection on dominant S-alleles results in greater fixation of linked deleterious mutations, while recessive S-alleles accumulate more linked deleterious mutations that are segregating. Hence, the structure rather than the overall magnitude of the linked genetic load differs between dominant and recessive S-alleles. Our results have consequences for the long-term evolution of new S-alleles, the evolution of dominance modifiers between them, and raise the question of why the non-recombining regions of some sex and mating type chromosomes expand over evolutionary times while others, such as the S-locus of the Brassicaceae, remain restricted to small chromosomal regions. [ABSTRACT FROM AUTHOR]

Frequencies of pharmacogenetic (PGx) variants are known to differ substantially across populations but much of the available PGx literature focuses on one or a few population groups, often defined in nonstandardized ways, or on a specific gene or variant. Guidelines produced by the Clinical Pharmacogenetic Implementation Consortium (CPIC) provide consistent methods of literature extraction, curation, and reporting, including comprehensive curation of allele frequency data across nine defined "biogeographic groups" from the PGx literature. We extracted data from 23 CPIC guidelines encompassing 19 genes to compare the sizes of the populations from each group and allele frequencies of altered function alleles across groups. The European group was the largest in the curated literature for 16 of the 19 genes, while the American and Oceanian groups were the smallest. Nearly 200 alleles were detected in nonreference groups that were not reported in the largest (reference) group. The genes CYP2B6 and CYP2C9 were more likely to have higher frequencies of altered function alleles in nonreference groups compared to the reference group, while the genes CYP4F2, DPYD, SLCO1B1, and UGT1A1 were less likely to have higher frequencies in nonreference groups. PGx allele frequencies and function differ substantially across nine biogeographic groups, all but two of which are underrepresented in available PGx data. Awareness of these differences and increased efforts to characterize the breadth of global PGx variation are needed to ensure that implementation of PGx‐guided drug selection does not further widen existing health disparities among populations currently underrepresented in PGx data. [ABSTRACT FROM AUTHOR]

Aim: To explore the correlation between Fat mass and objectivity associated gene (FTO) rs9939609 polymorphism and susceptibility to polycystic ovary syndrome. Methods: Case–control studies on the relationship between FTO rs9939609 A/T polymorphism and PCOS were searched in PubMed, EMBASE, and Web of Science according to inclusion and exclusion criteria. STATA 12.0 software was conducted for Meta‐analysis. Results: Nine case–control studies were included, including 1410 cases in PCOS group and 1223 cases in healthy control group. The results of meta‐analysis showed that FTO rs9939609 gene polymorphism was associated with PCOS susceptibility, and the risk of developing PCOS was 1.19 times higher for T alleles carriers than for A alleles carriers, and some similar associations were observed in Asian populations. Conclusions: In summary, FTO rs9939609 gene polymorphism is significantly associated with PCOS susceptibility, especially in Asian populations. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this research is to carry out a genetic cohort study of SMA patients in the Eastern Anatolia region of Turkey, investigating the genetic causes of the illness, specifically the impact of the number of SMN1 and SMN2 gene alleles on the course of the disease. Methods: The Erzurum Medical Faculty of Health Sciences at Erzurum City Hospital gave ethical approval for the study to be conducted. A total of 348 patients with an initial diagnosis of SMA underwent genetic testing. Using the PCR-RFLP approach, deletions of exons 7 and 8 in the SMN1 and SMN2 genes were examined. Results: In examining the allele counts in the exon 7 and exon 8 regions of the SMN1 and SMN2 genes, 41 patients were found to have no copies of the SMN1 gene (0 alleles), while 112 people were identified as possible carriers. Analysis of the SMN2 gene's allele distribution revealed a substantial relationship between the number of alleles and the clinical severity of the disease. Conclusion: The number of alleles in the SMN1 and SMN2 genes influences the course of the disease, as demonstrated by the genetic cohort analysis of SMA patients in the Eastern Anatolia region of Turkey presented in this paper. The findings indicate that sex does not influence the frequency of the disease or carrier status, offering significant new insights into the genetic diagnosis and treatment of SMA. The study also emphasizes the importance of establishing local genetic screening programs and counseling services to facilitate early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Four mitochondrial phylogroups are distinguished in the European pine marten (Martes martes), two of which, FNR1/2, are shared with the more easterly sister species, the sable (Martes zibellina). Here, we found that the phylogroup frequencies differed markedly between the southern Finland and western Russia populations in the eastern part of the range of Martes martes, suggesting differential introgression from M. zibellina in these regions. We also examined the diversity of a protein-coding gene, MHC class II DRB, in these two Martes species. We detected 16 functional Martes martes DRB alleles (Mama-DRBs), including several codons that seem to have undergone positive selection, and eight presumed pseudogenes (Mama-DRB*PSs); some alleles/pseudogenes were geographically widespread and others restricted. In a broader carnivoran DRB tree, all Mama-DRBs grouped within a mustelid clade, four in a basal group comprising alleles from early-diverged species and the others in a derived group containing alleles from more recently diverged species. Many alleles showed trans-species polymorphism, suggesting that Mama-DRBs have evolved under pathogen-driven balancing selection. Three of six Mama-DRBs and one of four pseudogenes shared with Martes zibellina were restricted to the FNR1/2 mitochondrial DNA phylogroups, pointing to the possibility that genetic introgression from Martes zibellina might have contributed to Mama-DRB diversity and thus adaptability. [ABSTRACT FROM AUTHOR]

A small family of low-molecular-weight intracellular fatty acid-binding proteins (FABPs), influence the transport and metabolism of long-chain fatty acids in the cell, as among them is fatty acid-binding protein 3 (FABP3). The aim of the study was to investigate the effect of genotypic variation in SNP3 of the FABP3 gene on milk productivity and fertility in Awassi sheep. The study included 61 ewes of different ages from a private herd in the village of Sredkovets, Shumen district, Bulgaria. Animal genotypes were established using PCR-RFLP analysis with application of restriction enzyme BseDI and subsequent gel electrophoresis. The presence of two alleles was found - the wild allele A (with fragments - 36 bp and 186 bp) and the mutant allele G (with fragments of 36 bp, 43 bp and 143 bp) with frequencies of 0.91 and 0.09, respectively, as well as availability of two genotypes - the homozygous wild GG and the heterozygous AG with frequencies of 0.84 and 0.16, respectively. No individuals with the homozygous mutant genotype AA were detected. A proven higher milk productivity was found in the ewes carriers of the homozygous genotype GG (126,989 l) compared to those with the heterozygous genotype AG (122,141 l). No significant differences in litter size were found between carriers of the two genotypes. [ABSTRACT FROM AUTHOR]

Stroke remained the second leading cause of death globally in 2019. The antiplatelet drug clopidogrel is used to keep blood clots from forming in people who have experienced a stroke. Although most people find clopidogrel to be safe and beneficial, there is inevitably a range in how each patient responds.The review covers about Clopidogrel resistance in stroke patients, their risk factors and the methods to identify it. Clopidogrel resistance is characterized as the drug's inability to prevent the target enzyme from acting. The prognosis of patients with ischemic stroke and the responsiveness to clopidogrel are significantly impacted by the various genetic polymorphism CYP2C19 genotypes. The two primary mutant alleles, CYP2C19 *2 and CYP2C19 *3, have been found to be the most prevalent genotypes. Better mRS scores six months after treatment showed a higher response rate in patients without these CYP2C19 variant alleles. Other factors are drug-drug interaction (proton pump inhibitors), demographics (age, sex, social history), comorbid conditions, etc. Blood samples for testing platelet reactivity were drawn one month after discharge from a peripheral blood sample. Several methods are used to identify the clopidogrel resistance. Some of them are ADP-Induced platelet aggregation, Platelet Reactivity Index VASP, Verify Now Assay, TEG Analyzer, Plasma microRNA-223. Drugs that are not prodrugs and whose metabolism is not dependent upon CYP2C19 can be selected as a superior alternative in case of CR. Ticagrelor is one such effective substitute. Proton pump inhibitors and clopidogrel should only be used concurrently in patients with reliable clinical indications. [ABSTRACT FROM AUTHOR]

Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions. Uninterrupted AAG expansions are significantly enriched in patients with ataxia from a lower threshold (180–200 repeats) than previously reported based on expansion size alone. Conversely, AAGGAG hexameric expansions are equally frequent in patients and controls. Distinct 5' flanking regions, interruptions and pre-repeat sequences correlate with repeat size. Furthermore, pure AAG (pathogenic) and AAGGAG (non-pathogenic) repeats form different secondary structures. Regardless of expansion size, SCA27B is a recognizable clinical entity characterized by frequent episodic ataxia and downbeat nystagmus, similar to the presentation observed in a family with a previously unreported nonsense variant (SCA27A). Overall, this study suggests that SCA27B is a major overlooked cause of adult-onset ataxia, accounting for 23–31% of unsolved patients. We strongly recommend re-evaluating pathogenic thresholds and integrating expansion sequencing into the molecular diagnostic process. Repeat expansions in the FGF14 gene can cause late-onset cerebellar ataxia (SCA27B), however the defining features of pathogenic expansions remain uncertain. Here, the authors compare the sequence and structure of FGF14 repeat expansions in patients and controls, leading them to suggest a lower pathogenic threshold and emphasizing the importance of sequencing the full expansion for accurate interpretation. [ABSTRACT FROM AUTHOR]

Background & Objective: The relationship between vitamin D receptor (VDR). Polymorphisms, and diabetes remain uncertain. This study aimed to examine the potential correlation between type 2 diabetes mellitus (T2DM) and rs739837 single nucleotide polymorphism (SNP) in the Mazandaran province population. Materials & Methods: A case-control study was conducted, involving 100 individuals diagnosed with T2DM and 100 healthy controls, all residents of Mazandaran province. The extraction of genomic DNA and rs739837 polymorphism was genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: The data indicated a significant association between GT genotype and a decreased risk of T2DM (OR= 0.5135, 95%CI= 0.2759 to 0.9559, P=0.0355). Moreover, individuals carrying T allele showed a reduced likelihood of progressing T2DM (OR= 0.4657, 95%CI= 0.2564 to 0.8461, P=0.0121). Conclusion: The findings suggested that rs739837 polymorphism in the VDR gene may serve as a protective factor against T2DM in the studied population. Further research with larger samples is needed to confirm these results across different populations. [ABSTRACT FROM AUTHOR]

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This study aims to evaluate the association between tumor necrosis factor-α (TNF–α) single nucleotide polymorphisms and psoriasis vulgaris. This cross-sectional study involved 140 Vietnamese patients of Kinh ethnicity diagnosed with psoriasis vulgaris. The diagnosis of psoriasis vulgaris was based on clinical signs and symptoms. We used Sanger sequencing to analyze two single nucleotide polymorphisms (SNPs), rs1799964 and rs1799724. Data were analyzed by SPSS 25. SNP rs1799964 has the highest rate of TT genotype at 62.1%, more than double the heterozygous TC genotype at 30%, CC genotype has the lowest rate at 7.9%. CC genotype of SNP rs1799724 accounted for 90%, and no homozygous genotype TT was detected. No statistically significant association was found between both SNPs and clinical features (p>0.05). The Psoriasis Area and Severity Index (PASI) was significantly lower in patients with variant alleles (p=0.021). Our data show a significant negative association between SNP variant alleles and the disease's severity. Studies with larger sample sizes and more biochemical indices may help identify reliably predictive markers for these SNPs. [ABSTRACT FROM AUTHOR]

In forensic DNA laboratories, it is important to conduct internal validations of the commercially available kits of short tandem repeat (STR) loci and to investigate their individual and combined effectiveness. This study aims to report on a comparative investigation of the forensic kits used in our laboratory and their combinations in analysing low-copy-number (LCN) human DNA samples. We used five partly overlapping multiplex kits with different marker configurations from different manufacturers: the NGM SelectTM PCR Amplification Kit, NGM DetectTM, the GlobalFilerTM Amplification Kit (Applied BiosystemTM, Foster City, CA, USA), the PowerPlex® Fusion 6C System (Promega Co., Madison, WI, USA) and the Investigator® 24plex QS Kit (Qiagen GmbH, Hilden, Germany). The efficacy of the kits was scrutinised by specific criteria, such as allelic dropout rate, the individually calculated Likelihood Ratio (LR) of consensus profiles and the LR value of the composite profile produced by the combined profiles of two kits. According to the results, the pairing of PowerPlex® Fusion 6C System and Investigator® 24plex QS produced the lowest, while the pairing of the NGM DetectTM and GlobalFilerTM kits provided the highest LR value. In summary, our study is meant to aid the selection of the optimal kit combination for samples of different qualities. [ABSTRACT FROM AUTHOR]

The present study explored the association between a point mutation (g.857G>A) in the IGF-1 gene and performance traits in Harnali Sheep. Genomic DNA was extracted from 110 Harnali sheep using an Automated Maxell RSC DNA/RNA purification system. A 294 bp fragment, covering the 5′ flanking region of the IGF-1 gene, was amplified with specific primers. The resulting PCR product, harboring the g.857G>A mutation, was digested with the Hae II enzyme to determine genotypes. The frequency of the A allele of the IGF-1 gene was higher (0.59) in the studied Harnali sheep population, with the GA genotype being the most prevalent (0.64). The presence of the A allele was associated with higher body weights, suggesting its potential as a selection criterion for improving flock performance. Furthermore, the GA genotype was linked to a lower average age at first lambing (727.93 days) compared to the GG genotype (753.08 days). The A allele was linked to higher body weights, while the GA genotype was associated with a lower age at first lambing. These findings highlight the potential of these genetic markers for improving breeding strategies and enhancing flock performance. However, validation on larger samples is warranted. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Similar phenotypes can evolve repeatedly under the same evolutionary pressures. A compelling example is the evolution of pigment loss and eye loss in cave‐dwelling animals. While specific genomic regions or genes associated with these phenotypes have been identified in model species, it remains uncertain whether a bias towards particular genetic mechanisms exists. An isopod crustacean, Asellus aquaticus, is an ideal model organism to investigate this phenomenon. It inhabits surface freshwaters throughout Europe but has colonized groundwater on multiple independent occasions and evolved several cave populations with distinct ecomorphology. Previous studies have demonstrated that three different cave populations utilized common genetic regions, potentially the same genes, in the evolution of pigment and eye loss. Expanding on this, we conducted analysis on two additional cave populations, distinct either phylogenetically or biogeographically from those previously examined. We generated F2 hybrids from cave × surface crosses and tested phenotype‐genotype associations, as well as conducted complementation tests by crossing individuals from different cave populations. Our findings revealed that pigment loss and orange eye pigment in additional cave populations were associated with the same genomic regions as observed in the three previously tested cave populations. Moreover, the lack of complementation across all cross combinations suggests that the same gene likely drives pigment loss. These results substantiate a genetic bias in the recurrent evolution of pigment loss in this model system. Future investigations should focus on the cause behind this bias, possibly arising from allele recruitment from ancestral surface populations' genetic variation or advantageous allele effects via pleiotropy. Research highlights: Pigment loss in two cave populations was associated with the same genomic region as in previously tested ones.Pigment loss did not complement, so the same gene likely drives it in all cave populations.Results support a genetic bias in the recurrent evolution of pigment loss in caves. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the KISS1R gene are among the most critical potential causes of infertility. This gene plays a role in the regulation of the hypothalamus-pituitary-gonadal (HPG) axis and is used in the regulation of reproductive cycles and maturation of humans. The present study aimed to investigate the relationship between the Gly56Ala genetic variation of the KISS1R gene and infertility in a population of women in northern Iran. Materials & Methods: In this work, among the women referred to Al-Zahrai Hospital of Rasht (Gilan Province, Iran) 100 women (50 infertile and 50 healthy) with age range (35.1 ± 2.1) were examined as patient and control group, respectively. Blood samples were collected with a volume of 2 ml and poured into EDTA carrier tubes. The DNA was extracted from leukocytes using a GPP kit. Allele-specific polymerase chain reaction (AS-PCR) was used to determine the genotype of KISSIR gene polymorphism (rs397515615). Results: The findings indicated that there was no significant correlation in genotype distribution between patients and control subjects in the samples evaluated in Gilan Province, Iran (P=0.216). Conclusion: The Gly56Ala polymorphism of the KISS1R gene is not related to an increase in the risk of female infertility in the population of Gilan Province, Iran. Moreover, this gene is not considered a risk factor for female infertility in northern Iran. The change in the sampling location or size makes it possible to obtain different results. [ABSTRACT FROM AUTHOR]

Diverse rice germplasm comprising 112 genotypes was evaluated for yield traits across three environments. Pooled and environmentwise analysis of variance revealed heterogeneity in the data and significant environment interactions for all the yield traits. As per AMMI (additive main effects and multiplicative interaction) and GGE (genotype and genotype x environment interaction) biplots, the influence of environment was significant and varying on all the component yield traits including grain yield and was not significant in case of flowering date. Dry season at Maruteru in 2014–15 (E1) was the most discriminative and representative environment for favourable plant growth in terms of plant height, panicle number and panicle length. None of the environments represented ideal environment for the favourable expression of grain number while all the environments were equally informative for thousand grain weight and grain yield. Panicle number, grain number and thousand grain weight were contributing to grain yield across the environments. Three genotypes Panthdhan 12, Konark and Udaygiri were the most stable genotypes for grain yield with favourable combination of associated yield genes for all the traits, viz. 1000 grain weight, the number of grains per panicle, the number of filled grains per panicle, productive tillers and plant height with higher yield, and grouped in one cluster. Genotyping using previously reported markers revealed that favourable alleles of yield genes associated with the number of productive tillers were predominantly found followed by alleles for the number of grains/filled grains per panicle correlating with the superior phenotypic value of the respective trait. The information on association of yield stability with reported yield genes from this study is useful in marker-assisted breeding studies for yield improvement and can be confirmed with various sets of genotypes under multi-environment testing. The identified superior genotypes are potential components in future breeding programmes and the development of stable adaptable varieties. The present study suggests that yield stability could be effectively achieved with targeted improvement of component yield traits associated with favourable alleles. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3‐kinase γ (PI3Kγ) is G‐protein‐coupled receptor‐activated lipid kinase with both kinase‐dependent and kinase‐independent activity. Plenty of evidence have demonstrated that PI3Kγ participated in TAC and I/R‐induced myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in the PI3Kγ gene (PIK3CG) were associated with the prognosis of HF in the Chinese Han population. Through re‐sequencing and genotyping, we finally identified a common variant in the 3′UTR of PIK3CG strongly associated with the prognosis of HF in two‐stage population: adjusted p = 0.007, hazard ratio = 0.56 (0.36–0.85) in the first cohort and adjusted p = 0.024, hazard ratio = 0.39 (0.17–0.88) in the replicated cohort. A series of functional assays revealed that rs10215499‐A allele suppressed PIK3CG translation by facilitating has‐miR‐133a‐3p binding, but not the G allele. Subjects carrying the GG genotype showed higher mRNA and protein level than those with AA and AG genotype. Furthermore, overexpression of PIK3CG could protect AC16 from hypoxia/reoxygenation (H/R)‐induced apoptosis, while the case was opposite for PIK3CG silencing. In conclusion, common variant rs10215499 in the 3′‐UTR of PIK3CG might affect the prognosis of HF by interfering with miR‐133a‐3p binding and PIK3CG is a promising target for HF treatment in the future. [ABSTRACT FROM AUTHOR]

The pulse beetle, Callosobruchus spp., poses a threat to legumes by consuming the protein content of the grain, resulting in potential losses in storage ranging from 12 to 30%. Molecular marker technology helps to mitigate the breeding constraint in the development of bruchid resistance in green gram breeding programmes. In the present study, validation of locus-specific STSbr1 and STSbr2 markers linked with bruchid resistance was done using fifteen genotypes viz., VBN (Gg) 2 (susceptible) and Vigna radiata var. sublobata/2 (resistant), F1 hybrid, two susceptible and ten resistant RILs derived from the above parents. The marker STS br1 behaved as a dominant marker and produced an approximate allele size of 225 bp in the resistant parent, F1 hybrid and resistant RILs and absent in susceptible parent and susceptible RILs, which showed cent per cent co-segregation with bruchid resistance locus. Hence, it is concluded that STS br1 is linked with bruchid-resistant genes. The marker STS br2 behaved as a co-dominant marker and produced an approximate allele size of 470 bp in all the 15 genotypes evaluated (monomorphic) and did not differentiate the resistant and susceptible genotypes. The marker STS br1 could be used in marker-assisted selection to develop bruchid-resistant varieties and to screen the germplasm to identify bruchid-resistant donors in green gram. [ABSTRACT FROM AUTHOR]

Objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302. [ABSTRACT FROM AUTHOR]

The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes1. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies2,3. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks4. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis. We focused on targeting the unmutated peptide QYNPIRTTF discovered on HLA-A*24:02, which is derived from the neuroblastoma-dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, we developed peptide-centric chimeric antigen receptors (PC-CARs) through a counter panning strategy using predicted potentially cross-reactive peptides. We further proposed that PC-CARs can recognize peptides on additional HLA allotypes when presenting a similar overall molecular surface. Informed by our computational modelling results, we show that PHOX2B PC-CARs also recognize QYNPIRTTF presented by HLA-A*23:01, the most common non-A2 allele in people with African ancestry. Finally, we demonstrate potent and specific killing of neuroblastoma cells expressing these HLAs in vitro and complete tumour regression in mice. These data suggest that PC-CARs have the potential to expand the pool of immunotherapeutic targets to include non-immunogenic intracellular oncoproteins and allow targeting through additional HLA allotypes in a clinical setting.

ImportanceCandida albicans is a commensal fungus that colonizes the human oral cavity and gastrointestinal tract but also causes mucosal as well as invasive disease. The expression of virulence traits in C. albicans clinical isolates is heterogeneous and the genetic basis of this heterogeneity is of high interest. The C. albicans reference strain SC5314 is highly invasive and expresses robust filamentation and biofilm formation relative to many other clinical isolates. Here, we show that SC5314 derivatives are heterozygous for the transcription factor Rob1 and contain an allele with a rare gain-of-function SNP that drives filamentation, biofilm formation, and virulence in a model of oropharyngeal candidiasis. These findings explain, in part, the outlier phenotype of the reference strain and highlight the role heterozygosity plays in the strain-to-strain variation of diploid fungal pathogens.

ImportanceThe development of therapeutics for patients who are positive for specific human leukocyte antigen (HLA) subtypes evokes the question of whether certain racial and ethnic groups are more or less likely to be eligible for novel products.ObjectiveTo determine whether racial and ethnic inequities were present with regard to trial eligibility in trials investigating a therapeutic restricted to patients with specific HLA subtypes.Design, setting, and participantsThis cross-sectional study included all clinical trials registered in ClinicalTrials.gov through March 18, 2022, that investigated an interventional study of a therapeutic strategy and restricted participants to those with at least 1 HLA subtype. Data were analyzed from May 8 to July 1, 2022.Main outcomes and measuresThe type of therapeutics used in trials, the condition under study, the HLA subtypes used, and the likelihood of being enrolled in such a trial according to race and ethnicity.ResultsOf 2135 trials identified, 263 met inclusion criteria. Overall, the estimated likelihood of being eligible for an HLA-based trial was 50.3%. Individuals of African American descent had the lowest likelihood of eligibility (33.0%), while being an individual of European descent conferred the highest (53.0%; 1.6 times more likely than African American individuals). Most trials studied anticancer therapeutics (258 [98.1%; 95% CI, 96.4%-99.7%]), and most were a therapeutic vaccine (179 [68.1%; 95% CI, 62.4%-73.7%]). The HLA-A*02:01 allele and the HLA-A2 serotype were the most frequent HLA subtypes for trial eligibility. The frequency of the HLA-A*02:01 allele in the population varied, with 11.9% (95% CI, 11.8%-12.0%) in African or African American individuals and 27.1% (95% CI, 27.1%-27.1%) in individuals of European descent.Conclusions and relevanceThe findings of this cross-sectional study suggest that enrollment restrictions for clinical trials investigating novel HLA therapeutics may be associated with racial and ethnic inequities with regard to trial eligibility. Overcoming these restrictions poses biological challenges, but solutions must be implemented to provide equal access to innovative strategies regardless of race or ethnicity.

The nomenclatures used to describe HLA and killer-cell immunoglobulin-like receptor (KIR) alleles distinguish unique nucleotide and peptide sequences, and patterns of expression, but are insufficient for describing genotyping results, as description of ambiguities and relations across loci require terminology beyond allele names. The genotype list (GL) String grammar describes genotyping results for genetic systems with defined nomenclatures, like HLA and KIR, documenting what is known and unknown about a given genotyping result. However, the accuracy of a GL String is dependent on the reference database version under which it was generated. Here, we describe the GL string code (GLSC) system, which associates each GL String with meta-data describing the specific reference context in which the GL String was created, and in which it should be interpreted. GLSC is a defined syntax for exchanging GL Strings in the context of a specific gene-family namespace, allele-name code-system, and pertinent reference database version. GLSC allows HLA and KIR genotyping data to be transmitted, parsed and interpreted in the appropriate context, in an unambiguous manner, on modern data-systems, including Health Level 7 Fast Healthcare Interoperability Resource systems. Technical specification for GLSC can be found at https://glstring.org.

Enlargement of the endolymphatic sac, duct, and vestibular aqueduct (EVA) is the most common inner ear malformation identified in patients with sensorineural hearing loss. EVA is associated with pathogenic variants in SLC26A4. However, in European-Caucasian populations, about 50% of patients with EVA carry no pathogenic alleles of SLC26A4. We tested for the presence of variants in CHD7, a gene known to be associated with CHARGE syndrome, Kallmann syndrome, and hypogonadotropic hypogonadism, in a cohort of 34 families with EVA subjects without pathogenic alleles of SLC26A4. In two families, NM_017780.4: c.3553A > G [p.(Met1185Val)] and c.5390G > C [p.(Gly1797Ala)] were detected as monoallelic CHD7 variants in patients with EVA. At least one subject from each family had additional signs or potential signs of CHARGE syndrome but did not meet diagnostic criteria for CHARGE. In silico modeling of these two missense substitutions predicted detrimental effects upon CHD7 protein structure. Consistent with a role of CHD7 in this tissue, Chd7 transcript and protein were detected in all epithelial cells of the endolymphatic duct and sac of the developing mouse inner ear. These results suggest that some CHD7 variants can cause nonsyndromic hearing loss and EVA. CHD7 should be included in DNA sequence analyses to detect pathogenic variants in EVA patients. Chd7 expression and mutant phenotype data in mice suggest that CHD7 contributes to the formation or function of the endolymphatic sac and duct.

The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk of Alzheimers disease (AD). To investigate potential mechanisms, we analyzed knockin mice expressing human TREM2-R47H from one mutant mouse Trem2 allele. TREM2-R47H mice showed increased seizure activity in response to an acute excitotoxin challenge, compared to wildtype controls or knockin mice expressing the common variant of human TREM2. TREM2-R47H also increased spontaneous thalamocortical epileptiform activity in App knockin mice expressing amyloid precursor proteins bearing autosomal dominant AD mutations and a humanized amyloid-β sequence. In mice with or without such App modifications, TREM2-R47H increased the density of putative synapses in cortical regions without amyloid plaques. TREM2-R47H did not affect synaptic density in hippocampal regions with or without plaques. We conclude that TREM2-R47H increases AD-related network hyperexcitability and that it may do so, at least in part, by causing an imbalance in synaptic densities across brain regions.

OBJECTIVES: Type I interferon (IFN) plays a role in the pathogenesis of systemic lupus erythematosus (SLE), but insufficient attention has been directed to the differences in IFN responses between ancestral populations. Here, we explored the expression of the interferon gene signatures (IGSs) in SLE patients of European ancestry (EA) and Asian ancestry (AsA). METHODS: We used gene set variation analysis with multiple IGS encompassing the response to both type 1 and type 2 IFN in isolated CD14+ monocytes, CD19+B cells, CD4+T cells and Natural Killer (NK) cells from patients with SLE stratified by self-identified ancestry. The expression of genes upstream of the IGS and influenced by lupus-associated risk alleles was also examined. Lastly, we employed machine learning (ML) models to assess the most important features classifying patients by disease activity. RESULTS: AsA patients with SLE exhibited greater enrichment in the IFN core and IFNA2 IGS compared with EA patients in all cell types examined and, in the presence and absence of autoantibodies. Overall, AsA patients with SLE demonstrated higher expression of genes upstream of the IGS than EA counterparts. ML with feature importance analysis indicated that IGS expression in NK cells, anti-dsDNA, complement levels and AsA status contributed to disease activity. CONCLUSIONS: AsA patients with SLE exhibited higher IGS than EA patients in all cell types regardless of autoantibody status, with enhanced expression of genetically associated genes upstream of the IGS potentially contributing. AsA, along with the IGS in NK cells, anti-dsDNA and complement, independently influenced SLE disease activity.

Breeding perennial tree crops often requires prediction of mature performance from juvenile data. To assess the utility of juvenile screens to predict salinity tolerance of mature pistachio trees, we compared performance of 3-month ungrafted seedlings and 4-year-old grafted rootstocks under salinity stress. The QTL allele associated with higher salt exclusion from seedling leaves conferred lower growth in saline field conditions, suggesting that mapping QTL in seedlings may be easier than discerning the optimal allele for field performance.

The article discusses a study by J. R. González and colleagues which examined the predictive value of Global-Positioning-System and multiomics data for noncontract injury occurrence in 24 female football players. Topics include finding on prognostic models developed with inadequate sample size and result of design analyses of any effect observed for the rate alleles of the target polymorphisms.

The buffalo population raised in Brazil tend to show loss of genetic variability over generations, with significant estimates of inbreeding depression. Besides mating genetically distant individuals, other tools can be used to maintain/increase the genetic variability of the population, such as the use of PRDM9 genotypes. The PRDM9 gene promotes the creation of crossing-over points across the genome, with each allele promoting the creation of a different hotspot. Thus, increasing the frequency of less frequent alleles in the population, allows the emergence of new haplotypes and increases genetic variability. So, this study aimed to characterize the alleles of the PRDM9 gene circulating in the Murrah, Jaffarabadi, and Mediterranean breeds and verify their potential impact on genetic diversity management within the populations. The three alleles (B, C and D) were found in the three breeds at different frequencies, as well as the genotypic frequencies. The mating of different homozygous genotypes and genotypes carrying less frequent alleles may increase recombination rates and population variability. Four described variants and one new variant for allele D were found by sequencing. It was verified that it is possible to mate sires and dams with different PRDM9 genotypes in order to try to increase genetic variability in buffalo populations, improving the matings choices in buffalo breeding, helping to maintain production levels.

ABSTRACT Objectives Peri‐implantitis (PI) is the most common biological issue surrounding dental implants. According to current knowledge, the aforementioned complication is not equally distributed across different populations, and gene polymorphisms might be one contributing factor. The current study aimed to examine the association between gene polymorphisms of matrix metalloproteinase‐ (MMP‐) 1, ‐2, ‐3, ‐7, and ‐13 with PI in an Iranian demographic. Material and Methods The study's sample included 50 subjects suffering from PI and 89 healthy controls. From each participant, a venous blood sample of 5 cc was obtained, and DNA was extracted. Gene polymorphisms were investigated using restriction fragment length polymorphism polymerase chain reaction (RFLP‐PCR) combined with electrophoresis. Statistical analyses were done using the Pearson chi‐square test, odds ratio, and t‐test via SPSS version 28. Results The MMP‐3 (‐1171 5A/6A) and MMP‐7 (‐181 A/G) gene polymorphisms were significantly different between the patients with PI and healthy controls (PV 0.05). Moreover, the presence of the 6 A allele in the MMP‐3 (‐1171 5A/6A) genotype resulted in a significant decrease in PI risk (PV

Carling et al. report that late-onset Alzheimer's disease (LOAD) risk alleles drive cellular senescence, a hallmark of aging, in a tau- and sex-dependent manner. Mechanistic insights into interactions among genetic risk, biological aging, and sex differences in LOAD are presented. [ABSTRACT FROM AUTHOR]

Identification of four novel HLA‐DRB1 alleles by next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Four novel HLA‐B alleles are described from bone marrow volunteers of Russian Registry. [ABSTRACT FROM AUTHOR]

Four novel HLA alleles HLA‐A*02:01:222, ‐B*07:02:104, ‐C*07:02:156 and ‐DQB1*06:03:51 alleles detected during routine next generation sequencing. [ABSTRACT FROM AUTHOR]

Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment. However, there is a highly incomplete understanding of the genetic determinants of LATE neuropathologic changes (LATE-NC) in diverse populations. The defining neuropathologic feature of LATE-NC is TDP-43 proteinopathy, often with comorbid hippocampal sclerosis (HS). In terms of genetic risk factors, LATE-NC and/or HS are associated with single nucleotide variants (SNVs) in 3 genes-TMEM106B (rs1990622), GRN (rs5848), and ABCC9 (rs1914361 and rs701478). We evaluated these 3 genes in convenience samples of individuals of African ancestry. The allele frequencies of the LATE-associated alleles were significantly different between persons of primarily African (versus European) ancestry: In persons of African ancestry, the risk-associated alleles for TMEM106B and ABCC9 were less frequent, whereas the risk allele in GRN was more frequent. We performed an exploratory analysis of data from African-American subjects processed by the Alzheimer's Disease Genomics Consortium, with a subset of African-American participants (n = 166) having corroborating neuropathologic data through the National Alzheimer's Coordinating Center (NACC). In this limited-size sample, the ABCC9/rs1914361 SNV was associated with HS pathology. More work is required concerning the genetic factors influencing non-Alzheimer disease pathology such as LATE-NC in diverse cohorts.