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Genomic Loci of Radiation-induced Lung Disease in a Mouse Model: Refinement and Candidate Gene Analysis.

Susceptibility to radiation-induced lung disease differs among people and among inbred strains of mice; C3H/HeJ mice develop early onset distress from pneumonitis and C57BL/6J mice present later onset pneumonitis with fibrosis. Previous studies revealed C3H/HeJ alleles at a 28 Mb locus on chromosome 2 to be linked to early onset distress and at an 18 Mb locus on chromosome 17 (called Radpf1 for radiation-induced pulmonary fibrosis-1) to decrease fibrosis in whole-thorax irradiated mice. To potentially reduce these genomic intervals, parental chr17-subcongenic mice with 0.71 Mb of C3H/HeJ allel…

Гены второго класса HLA связаны с множественным склерозом: иммуногенетическое прогнозирование среди многих склерозов иорданских пациентов.

Множественный склероз (MS) — вспыльчивая аутоиммунная болезнь, затрагивающая центральную нервную систему (КНС). Патогенез MS характеризуется нейронной аксонной дегенерацией и демиэлизацией. Среди генов, которые повышают риск склероза, есть гены второго класса HLA. Цель этого исследования заключалась в изучении роли генов HLA-DRB1 и HLA-DQB1 ( впервые) в иорданских пациентах, больных MS, и их связи с заболеваниями MS. Были исследованы связи этих генов с другими клиническими особенностями, такими, как оптический неврит, сенсорное расстройство и симптомы сетчатки головного мозга у пациентов MS, а

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system (CNS). The pathogenesis of MS is characte … s indicated an association between HLA-DRB1 * 03:01 (Pc =  0.01) and HLA-DRB1 * 04:01 (Pc =  0.004) alleles with Jordanian MS patients. In addition, a significant linkage between HLA-DRB1 * 15:01 and HLA-DQB1 * 06:01 alleles (Pc ≤  0.001 and Pc =  0.012, respectively) were presented among Jordanian MS patients with optic neuritis compared to Jordanian MS …

Allosensitisation in NHP results in cross-reactive anti-SLA antibodies not detected by a lymphocyte-based flow cytometry crossmatch.

Xenotransplantation is a potential option for individuals for whom an acceptable human allograft is unavailable. Individuals with broadly re … SLA. The cross-reactive IgG after allosensitisation were predicted by comparing the recipient Mamu alleles against its previous allograft donor Mamu alleles and the donor pig SLA alleles. Our study suggests that allosensitisation could elevate cross-reactive antibodies, but a more sensitive assay than a cell-based FXM is required to detect them. The MHC …

Anthrax Vaccination, Gulf War Illness, and Human Leukocyte Antigen (HLA).

We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War … to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high bin …

Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.

Small molecule drugs known as modulators can treat ~90% of people with cystic fibrosis (CF), but do not work for premature termination codon variants such as W1282X (c.3846G>A). Here we evaluated two gene editing strategies, Adenine Base Editing (ABE) to correct W1282X, and Homology-Independent Targeted Integration (HITI) of a CFTR superexon comprising exons 23-27 (SE23-27) to enable expression of a CFTR mRNA without W1282X. In Flp-In-293 cells stably expressing a CFTR expression minigene bearing W1282X, ABE corrected 24% of W1282X alleles, rescued CFTR mRNA from nonsense mediated decay and re…

Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies.

PURPOSE: Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-Eas … 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (R …

Primary open-angle glaucoma risk prediction with ABCA1 and LOC102723944 variants and their genotype-phenotype correlations in southern Chinese population.

Glaucoma is a leading cause of irreversible visual impairment and blindness worldwide. Previous genome-wide association studies have identif … HTG (P = 2.08 × 10-4, OR = 0.70). Joint analysis showed that carriers of homozygous non-protective alleles of ABCA1 rs2487032 and LOC102723944 rs6596830 had 2.99-fold higher risk of POAG (P = 1.27 × 10-3) when compared to those carrying homozygous non-risk alleles. Patients with POAG carrying ABCA1 rs2487032 G allele had higher HDL cholesterol, and those …

Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes.

BACKGROUND: FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 ( APOL1 ) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors. …

High-resolution HLA genotyping in inclusion body myositis refines 8.1 ancestral haplotype association to DRB1*03:01:01 and highlights pathogenic role of arginine-74 of DRβ1 chain.

OBJECTIVES: Inclusion body myositis (IBM) is a progressive inflammatory-degenerative muscle disease of older individuals, with some patients producing anti-cytosolic 5'-nucleotidase 1A (NT5C1A, aka cN1A) antibodies. Human Leukocyte Antigens (HLA) is the highest genetic risk factor for developing IBM. In this study, we aimed to further define the contribution of HLA alleles to IBM and the production of anti-cN1A antibodies. METHODS: We HLA haplotyped a Western Australian cohort of 113 Caucasian IBM patients and 112 ethnically matched controls using Illumina next-generation sequencing. Allele f…

Molecular characteristics of hereditary red blood cell membrane disorders in Thailand: a multi-center registry.

Red blood cell (RBC) membrane disorders represent a significant category of hereditary hemolytic anemia; however, information from Southeast … sequencing. The primary causative gene for HE and HPP was SPTB, accounting for 28 out of 29 studied alleles for HE and 56 of 56 studied alleles for HPP. In the case of HS, dominant sporadic mutations in the ANK1 gene (n=4) and SPTB gene (n=3) were identified as the underlying cause. Notably, the four most common variants causing HE and HPP were SPTB Provi …

Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018.

BACKGROUND: Resistance to anti-malarial drugs is associated with polymorphisms in target genes and surveillance for these molecular markers … 34, C3M69, Poly α, TA1, TA109, 2490, and PfPK2) was assessed. RESULTS: All isolates carried mutant alleles for pfcrt (K76T and N75E), and for pfdhfr (N51I and S108N), while for pfdhps, mutations were observed only for codon A437G (32/73, 43.8%). Fifty samples (58.8%) showed a complete neutral microsatellites (NMS) profile. The low mean number of alleles …

Clinical Outcomes After Percutaneous Coronary Intervention Over Time on the Basis of CYP2C19 Polymorphisms.

The aim of this study was to investigate the association between CYP2C19 gene polymorphisms and the risk of cardiovascular events in the ear … t 90 days and 1 year post-PCI. Of 1341 patients, 161 (12.0%) had 2 copies of loss-of-function (LOF) alleles, 621(46.3%) had one LOF allele, and 559 (41.7%) had no LOF allele. At the 3-month follow-up, the primary outcome events were more frequent in carriers of 2 LOF alleles (5.6%) than in noncarriers (1.8%) [adjusted hazard ratio (HR) 2.944, 95% confiden …

Cluster of Differentiation 24 Polymorphism Has No Significant Association with Chronic Hepatitis B Virus Infection in the Chinese Han Population: A Family-Based Association Study.

OBJECTIVE: Studies have shown that cluster of differentiation (CD) 24 gene polymorphism is associated with several diseases. Among these, ch … susceptibility to CHB. RESULTS: In the 478 patients with CHB, the frequencies of CD24 P170 T and C alleles were 35.5% and 64.5%, respectively, and the frequencies of CD24 P170 CC, CT, and TT genotypes were 39.3%, 50.4% and 10.3%, respectively. In a CD24 single-locus analysis by a family-based association test of P170 polymorphisms, T and C were not signi …

Next-generation sequencing and genotype association studies reveal the association of HLA-DRB3*02:02 with delayed hypersensitivity to penicillins.

BACKGROUND: Nonimmediate (delayed)-allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factor … ersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. RESULTS: The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk o …

Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes.

OBJECTIVE: The greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region to identify novel human leucocyte antigen (HLA) genetic variants associated with SSc susceptibility and its main clinical and serological subtypes. METHODS: 9095 patients with SSc and 17 584 controls genome-wide genotyped were used to impute and test single-nucleotide polymorphisms (SNPs) across the MHC, classical HLA alleles and their composite amino acid residues. Addi…

Gallbladder stone formation in Iraqi patients is associated with bacterial infection and HLA class II-DRB1 antigens.

BACKGROUND: Gallbladder stone is recently increased among the Iraqi society due to many risk factors such as bacterial infection and some HLA class II antigens. AIM(S): This study investigates the types of bacterial infection and HLA-DRB1 antigens' ratio that may be correlated with gallbladder stone formation. Setting and Design: The study included 45 patients and the same number of healthy individuals as a control group. Patients were with multiple gallstones. Gallstone bacterial culture was demonstrated to diagnose viable bacteria. HLA-DRB1 alleles' frequency was investigated using sequence…

RHD genotyping of serological weak D phenotypes in the Iranian blood donors and patients.

BACKGROUND: Most prevalent weak D types in the Caucasians molecularly defined weak D types 1, 2 or 3 and can be managed safely as RhD-positive, conserving limited supplies of RhD-negative RBCs. Therefore, identification of RHD alleles prevalence in each population could improve the policies related to accuracy of RhD typing. The aim of this study was to determine the frequency of RHD variant alleles among donors and patients for the first time in Iran. MATERIALS AND METHODS: RHD genotyping was performed on 100 blood donor and patient samples with weak D phenotype. PCR-SSP and DNA sequencing w…

The Classic Lobe Eye Phenotype of Drosophila Is Caused by Transposon Insertion-Induced Misexpression of a Zinc-Finger Transcription Factor.

Drosophila Lobe (L) alleles were first discovered ∼100 years ago as spontaneous dominant mutants with characteristic developmental eye defects. However, the molecular basis for L dominant eye phenotypes has not been clearly understood. A previous work reported identification of CG10109/PRAS40 as the L gene, but subsequent analyses suggested that PRAS40 may not be related to L Here, we revisited the L gene to clarify this discrepancy and understand the basis for the dominance of L mutations. Genetic analysis localized the L gene to Oaz, which encodes a homolog of the vertebrate zinc finger prot…

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing.

The emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While the alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding the molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole-genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa coefficient, 0.…

Association of common genetic variants with brain microbleeds: A genome-wide association study.

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed genome-wide … nd infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs. RESULTS: BMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region r …