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1.
Braz. j. biol ; 83: e247422, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1285631

RESUMO

Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.


Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.


Assuntos
Plasmodium falciparum/genética , Antimaláricos/farmacologia , Paquistão , Proteínas de Membrana Transportadoras/genética , Resistência a Medicamentos/genética , Proteínas de Protozoários/genética , Cloroquina/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Alelos
2.
Gigascience ; 112022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35333302

RESUMO

BACKGROUND: Cassava (Manihot esculenta) is an important clonally propagated food crop in tropical and subtropical regions worldwide. Genetic gain by molecular breeding has been limited, partially because cassava is a highly heterozygous crop with a repetitive and difficult-to-assemble genome. FINDINGS: Here we demonstrate that Pacific Biosciences high-fidelity (HiFi) sequencing reads, in combination with the assembler hifiasm, produced genome assemblies at near complete haplotype resolution with higher continuity and accuracy compared to conventional long sequencing reads. We present 2 chromosome-scale haploid genomes phased with Hi-C technology for the diploid African cassava variety TME204. With consensus accuracy >QV46, contig N50 >18 Mb, BUSCO completeness of 99%, and 35k phased gene loci, it is the most accurate, continuous, complete, and haplotype-resolved cassava genome assembly so far. Ab initio gene prediction with RNA-seq data and Iso-Seq transcripts identified abundant novel gene loci, with enriched functionality related to chromatin organization, meristem development, and cell responses. During tissue development, differentially expressed transcripts of different haplotype origins were enriched for different functionality. In each tissue, 20-30% of transcripts showed allele-specific expression (ASE) differences. ASE bias was often tissue specific and inconsistent across different tissues. Direction-shifting was observed in <2% of the ASE transcripts. Despite high gene synteny, the HiFi genome assembly revealed extensive chromosome rearrangements and abundant intra-genomic and inter-genomic divergent sequences, with large structural variations mostly related to LTR retrotransposons. We use the reference-quality assemblies to build a cassava pan-genome and demonstrate its importance in representing the genetic diversity of cassava for downstream reference-guided omics analysis and breeding. CONCLUSIONS: The phased and annotated chromosome pairs allow a systematic view of the heterozygous diploid genome organization in cassava with improved accuracy, completeness, and haplotype resolution. They will be a valuable resource for cassava breeding and research. Our study may also provide insights into developing cost-effective and efficient strategies for resolving complex genomes with high resolution, accuracy, and continuity.


Assuntos
Manihot , Alelos , Cromossomos , Diploide , Haplótipos , Manihot/genética , Melhoramento Vegetal , Análise de Sequência de DNA , Transcriptoma
3.
Forensic Sci Int Genet ; 57: 102661, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35063923

RESUMO

Non-self DNA is normally present on skin due to DNA transfer occurring during daily activities. The understanding of persistence and accumulation of foreign DNA on the neck can assist in the interpretation of DNA evidence collected from an assaulted victim. Establishing the composition and level of non-self DNA present is relevant, especially in cases where the victim cohabits with other individuals, such as partner and children. This study investigated the persistence and accumulation of non-self DNA on the neck, over the course of 24 h. DNA samples were collected from the neck of 20 adult volunteers at three time-points, on two days. The detection of a partner's DNA and DNA from unknown sources was studied in relation to the living arrangement and to the activities performed by each individual. An increased number of non-self alleles were detected over time. Partner's DNA was observed to accumulate during the day and to persist when an individual was absent from the shared home environment. DNA from unknown contributors was found on the neck of individuals that used public transport, attended public spaces and had social interactions. The data acquired from this study will help to increase knowledge on the composition of DNA present on an individual's neck in a daily situation.


Assuntos
Vítimas de Crime , DNA , Adulto , Alelos , Criança , DNA/genética , Humanos , Fatores de Tempo
4.
ACS Sens ; 7(3): 758-765, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35188365

RESUMO

Massive DNA testing requires novel technologies to support a sustainable health system. In recent years, DNA superstructures have emerged as alternative probes and transducers. We, herein, report a multiplexed and highly sensitive approach based on an allele-specific hybridization chain reaction (AS-HCR) in the array format to detect single-nucleotide variants. Fast isothermal amplification was developed before activating the HCR process on a chip to work with genomic DNA. The assay principle was demonstrated, and the variables for integrating the AS-HCR process and smartphone-based detection were also studied. The results were compared to a conventional polymerase reaction chain (PCR)-based test. The developed multiplex method enabled higher selectivity against single-base mismatch sequences at concentrations as low as 103 copies with a limit of detection of 0.7% of the mutant DNA percentage and good reproducibility (relative error: 5% for intra-assay and 17% for interassay). As proof of concept, the AS-HCR method was applied to clinical samples, including human cell cultures and biopsied tissues of cancer patients. Accurate identification of single-nucleotide mutations in KRAS and NRAS genes was validated, considering those obtained from the reference sequencing method. To conclude, AS-HCR is a rapid, simple, accurate, and cost-effective isothermal method that detects clinically relevant genetic variants and has a high potential for point-of-care demands.


Assuntos
Nucleotídeos , Smartphone , Alelos , Humanos , Hibridização de Ácido Nucleico/métodos , Reprodutibilidade dos Testes
5.
Pathol Oncol Res ; 28: 1610024, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498161

RESUMO

Cell-free DNA (cfDNA) in body fluids is invaluable for cancer diagnostics. Despite the impressive potential of liquid biopsies for the diagnostics of central nervous system (CNS) tumors, a number of challenges prevent introducing this approach into routine laboratory practice. In this study, we adopt a protocol for sensitive detection of the H3 K27M somatic variant in cerebrospinal fluid (CSF) by using digital polymerase chain reaction (dPCR). Optimization of the protocol was carried out stepwise, including preamplification of the H3 target region and adjustment of dPCR conditions. The optimized protocol allowed detection of the mutant allele starting from DNA quantities as low as 9 picograms. Analytical specificity was tested using a representative group of tumor tissue samples with known H3 K27M status, and no false-positive cases were detected. The protocol was applied to a series of CSF samples collected from patients with CNS tumors (n = 18) using two alternative dPCR platforms, QX200 Droplet Digital PCR system (Bio-Rad) and QIAcuity Digital PCR System (Qiagen). In three out of four CSF specimens collected from patients with H3 K27M-positive diffuse midline glioma, both platforms allowed detection of the mutant allele. The use of ventricular access for CSF collection appears preferential, as lumbar CSF samples may produce ambiguous results. All CSF samples collected from patients with H3 wild-type tumors were qualified as H3 K27M-negative. High agreement of the quantitative data obtained with the two platforms demonstrates universality of the approach.


Assuntos
Ácidos Nucleicos Livres , Glioma , Alelos , Histonas/genética , Humanos , Biópsia Líquida , Reação em Cadeia da Polimerase
6.
Iran J Allergy Asthma Immunol ; 21(2): 189-196, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35490272

RESUMO

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in white Caucasians. It affects many organs including the lung, pancreas, and liver. Whilst CF is a monogenic disease, several studies revealed a complex relationship between genotype and clinical phenotype of diseases. We examined the expression of human leukocyte antigen (HLA) class II alleles among Iranian CF patients with disease-related microbial infection. This study was conducted on 50 hospitalized CF patients (27 males, 23 females aged 15.5±6.5 years), and 50 healthy age- and gender-matched control subjects. 5ml whole blood was harvested and after isolation of genomic DNA, HLA-DRB1 subtypes were determined by single specific primer polymerase chain reaction methods. HLA-DRB1*10 was less frequent and HLA-DRB1*04 and HLA-DRB1*11 was the most frequent allele in CF patients, but none reached significance. HLA-DRB1*04 allele was frequently seen among16 CF patients with high serum IgE levels (430.25±219.7 IU/mL) and 27 CF patients that were positive for Pseudomonas aeruginosa colonization. A total of 31 CF patients had candida Albicans colonization in whom HLA-DRB1*11 was mostly seen. A total of 3 CF patients had allergic bronchopulmonary aspergillosis and two were diabetic. The DR4 and DR11 serotypes that recognize the HLA-DRB1*04 and HLA-DRB1*11 gene products respectively are not significantly enriched in the Iranian CF population. Further research should be conducted on DR4 and DR11 in CF patients to understand their possible role in infection and IgE expression.


Assuntos
Fibrose Cística , Alelos , Fibrose Cística/genética , Feminino , Cadeias HLA-DRB1/genética , Humanos , Imunoglobulina E , Irã (Geográfico) , Masculino
7.
Rinsho Ketsueki ; 63(4): 277-285, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35491217

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare and fatal thrombotic disorder characterized by impaired enzyme activity of von Willebrand factor cleaving protease, also known as ADAMTS13. Immune-mediated TTP (iTTP) is an acquired form of TTP caused by the production of auto-antibodies against ADAMTS13. The pathophysiology of autoimmune disorders is multifactorial, with several human leukocyte antigen (HLA) alleles identified as a genetic risk factor for autoimmune diseases known as susceptible HLA. In the early 2010s, three distinct European groups revealed that DRB1*11 is one of the most susceptible alleles in acquiring iTTP among Caucasians based on HLA typing data. Several in silico predictions for allele-restricted ADAMTS13 epitopes against T cells are made in this context, followed by an in vitro validation employing mass spectrometry using eluted peptides and T-cell assays. However, similar analyses in a genetically distinct Japanese population have not yet been conducted. We used next-generation sequencing to perform HLA typing for 52 Japanese patients with iTTP from 19 institutes. Our detailed analysis revealed that the specific allele DRB1*08:03 was identified as a genetic risk factor for iTTP in Japanese patients, but there were no statistically significant differences in the allele frequency of DRB1*11 between iTTP and healthy controls.


Assuntos
Púrpura Trombocitopênica Trombótica , Alelos , Suscetibilidade a Doenças/complicações , Teste de Histocompatibilidade/efeitos adversos , Humanos , Púrpura Trombocitopênica Trombótica/genética , Fatores de Risco
8.
J Clin Invest ; 132(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499084

RESUMO

Autosomal dominant disorders present unique challenges, as therapeutics must often distinguish between healthy and diseased alleles while maintaining high efficiency, specificity, and safety. For this task, CRISPR/Cas remains particularly promising. Various CRISPR/Cas systems, like homology-directed repair, base editors, and prime editors, have been demonstrated to selectively edit mutant alleles either by incorporating these mutations into sgRNA sequences (near the protospacer-adjacent motif ["near the PAM"]) or by targeting a novel PAM generated by the mutation ("in the PAM"). However, these probability-based designs are not always assured, necessitating generalized, mutation-agnostic strategies like ablate-and-replace and single-nucleotide polymorphism editing. Here, we detail recent advancements in CRISPR therapeutics to treat a wide range of autosomal dominant disorders and discuss how they are altering the landscape for future therapies.


Assuntos
Sistemas CRISPR-Cas , Alelos , Mutação
9.
Pan Afr Med J ; 41: 149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35519172

RESUMO

Introduction: human leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease. Methods: an analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status. Results: the HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB3*1 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB5*2 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040). Conclusion: the higher frequencies of HLA-DRB5*2 and HLA-DRB1*14 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population.


Assuntos
Infecções por HIV , Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Pulmonar , Adulto , Alelos , Estudos Transversais , Frequência do Gene , Cadeias HLA-DRB1/genética , Humanos , Quênia , Tuberculose Latente/epidemiologia , Tuberculose Latente/genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/genética
10.
Sci Rep ; 12(1): 7235, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508592

RESUMO

Human leukocyte antigen (HLA) genes have been implicated in cancer risk and shared heritability of different types of cancer. In this immunogenetic epidemiological study we first computed a Cancer-HLA profile for 30 cancer types characterized by the correlation between the prevalence of each cancer and the population frequency of 127 HLA alleles, and then used multidimensional scaling to evaluate the possible clustering of those Cancer-HLA associations. The results indicated the presence of three clusters, broadly reflecting digestive-skin-cervical cancers, reproductive and endocrine systems cancers, and brain and androgen-associated cancers. The clustering of cancer types documented here is discussed in terms of mechanisms underlying shared Cancer-HLA associations.


Assuntos
Imunogenética , Neoplasias do Colo do Útero , Alelos , Análise por Conglomerados , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA/genética , Humanos , Neoplasias do Colo do Útero/genética
11.
Neurol India ; 70(2): 729-732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35532648

RESUMO

Background: Genetic factors, including causal gene and modifier genes, contribute significantly in PD pathogenesis in an ethnicity-dependent manner. Dopamine Receptor 4 (DRD4), involved in dopamine metabolism is one such modifier locus for PD. Objective: To identify the potential association of DRD4 polymorphic variants with PD among Eastern Indians. Methods and Materials: PD-related DRD4 variants were genotyped among 291 PD patients and 265 ethnically matched controls from Eastern India. Results and Conclusion: Among the three DRD4 variants, only the 120 bp duplicated allele [P = 0.036; Odds ratio: 1.323; 95% CI: 1.014-1.725] and its homozygous genotype [P = 0.034; Odds ratio: 1.452; 95% CI: 1.025-2.057] were found as risk factors for overall PD and sporadic PD among Eastern Indians. However, no other disease-associated variant or haplotype was identified. Therefore, in conclusion, our study demonstrates that DRD4 plays a small role in PD pathogenesis among Eastern Indians.


Assuntos
Doença de Parkinson , Receptores Dopaminérgicos , Alelos , Genótipo , Haplótipos , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Polimorfismo Genético/genética , Receptores Dopaminérgicos/genética , Receptores de Dopamina D4/genética
12.
PLoS One ; 17(5): e0259327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35533190

RESUMO

The vast majority of human traits, including many disease phenotypes, are affected by alleles at numerous genomic loci. With a continually increasing set of variants with published clinical disease or biomarker associations, an easy-to-use tool for non-programmers to rapidly screen VCF files for risk alleles is needed. We have developed EZTraits as a tool to quickly evaluate genotype data against a set of rules defined by the user. These rules can be defined directly in the scripting language Lua, for genotype calls using variant ID (RS number) or chromosomal position. Alternatively, EZTraits can parse simple and intuitive text including concepts like 'any' or 'all'. Thus, EZTraits is designed to support rapid genetic analysis and hypothesis-testing by researchers, regardless of programming experience or technical background. The software is implemented in C++ and compiles and runs on Linux and MacOS. The source code is available under the MIT license from https://github.com/selfdecode/rd-eztraits.


Assuntos
Genômica , Software , Alelos , Genótipo , Fenótipo
13.
Nat Commun ; 13(1): 2595, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534475

RESUMO

Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the drive-induced DNA break is repaired by error-prone pathways, which creates mutations that disrupt the gRNA recognition sequence and prevent further gene-drive propagation. Here, we attempt to counteract this by encoding additional gRNAs that target the most commonly generated resistance alleles into the gene drive, allowing a second opportunity at gene-drive conversion. Our presented "double-tap" strategy improved drive efficiency by recycling resistance alleles. The double-tap drive also efficiently spreads in caged populations, outperforming the control drive. Overall, this double-tap strategy can be readily implemented in any CRISPR-based gene drive to improve performance, and similar approaches could benefit other systems suffering from low HDR frequencies, such as mammalian cells or mouse germline transformations.


Assuntos
Tecnologia de Impulso Genético , Alelos , Animais , Sistemas CRISPR-Cas/genética , Células Germinativas , Mamíferos/genética , Camundongos , RNA Guia/genética
14.
Orphanet J Rare Dis ; 17(1): 101, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35534869

RESUMO

BACKGROUND: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilaginous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves' disease (GD) and Hashimoto thyroiditis (HT). However, there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed the clinical and genetic profiles of patients in whom these diseases co-occur. METHODS: We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1, and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD. RESULTS: The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p = 2.44 × 10-7, binomial test). RP patients with GD tended to have nasal involvement (p = 0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p = 0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP. CONCLUSIONS: Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 characterize the subset of RP patients with GD, which may guide attempts to characterize a distinct subtype of RP for precision medicine.


Assuntos
Doenças Autoimunes , Doença de Graves , Doença de Hashimoto , Policondrite Recidivante , Alelos , Doenças Autoimunes/genética , Predisposição Genética para Doença , Doença de Graves/epidemiologia , Doença de Graves/genética , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/genética , Humanos , Policondrite Recidivante/epidemiologia , Policondrite Recidivante/genética
15.
Sci Adv ; 8(18): eabn8281, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35507656

RESUMO

Populations of widespread species are usually geographically distributed through contrasting stresses, but underlying genetic mechanisms controlling this adaptation remain largely unknown. Here, we show that in Arabidopsis thaliana, allelic changes in the cis-regulatory elements, WT box and W box, in the promoter of a key transcription factor associated with oxygen sensing, RELATED TO AP 2.12 (RAP2.12), are responsible for differentially regulating tolerance to drought and flooding. These two cis-elements are regulated by different transcription factors that downstream of RAP2.12 results in differential accumulation of hypoxia-responsive transcripts. The evolution from one cis-element haplotype to the other is associated with the colonization of humid environments from arid habitats. This gene thus promotes both drought and flooding adaptation via an adaptive mechanism that diversifies its regulation through noncoding alleles.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Alelos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a DNA/genética , Secas , Regulação da Expressão Gênica de Plantas , Umidade , Estresse Fisiológico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
Clin Appl Thromb Hemost ; 28: 10760296221092405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535404

RESUMO

To investigate the correlation between ApoE gene polymorphism and the risk of lower extremity arterial disease (LEAD) in T2DM patients of Han nationality in northern China. One hundred and fifty patients with T2DM and 150 patients with T2DM combined with LEAD were enrolled in the study and assigned to the control group and the case group, respectively. The results revealed that the number of epsilon 2 (ε2) genotype carriers in the case group was significantly lower than that in the control group (case vs control: 8.0% vs 15.4%), and the distribution of the ε2 allele frequency was similar to that of the genotype (case vs control: 4.0% vs 8.4%). A binary logistic regression analysis revealed that age, waist-to-hip ratio (WHR), and gender were risk factors for T2DM with LEAD and that the ApoE ε2 carriers was a protective factor (odds ratio [OR] 0.380; 95% confidence interval [CI] 0.162-0.892; P = .026). In male subjects, ε2 carriers were more common in the control group (case vs control:7.8% vs 24.1%), while epsilon 4 (ε4) carriers were more common in the case group (case vs control: 23.3% vs 8.6%); the distribution of frequency of ε2 and ε4 alleles was more common in the control group and the case group, respectively (case vs control: 3.9% vs 12.1%, 12.8% vs 5.2%). In male, age and WHR were risk factors for the disease, and being an ε2 carrier was a protective factor. Being an ApoE gene ε2 carrier is a protective factor for LEAD in male patients with T2DM that are of Han nationality in northern China.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Vasculares , Alelos , Apolipoproteína E2/genética , Apolipoproteínas E/genética , China , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Extremidade Inferior , Masculino , Polimorfismo Genético
17.
Biomed Res Int ; 2022: 6632442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528179

RESUMO

Diabetes mellitus (DM) is the ninth leading cause of death worldwide. Mortality from DM is largely attributed to disease complications. Glycemic control of DM patients reduces mortality. Studies indicated that the lack of glycemic control in DM patients could be influenced by the genetic background of the patients. Evidence suggests that adiponectin levels are dysregulated in DM patients with poor glycemic control. Serum adiponectin level is a heritable trait influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. It is hypothesized that SNPs in ADIPOQ could modify glycemic control in DM patients. To test this hypothesis, 375 type 2 DM (T2DM) patients were recruited. Patients were classified into good vs. poor glycemic control according to hemoglobin A1c levels. Study subjects were genotyped for variations of four SNPs in ADIPOQ (rs17300539, rs266729, rs2241766, and rs1501299). Adiponectin levels were measured from the serum. Our analysis showed that reduced serum adiponectin, a longer duration of treatment, and increased insulin resistance were all significant predictors of poor glycemic control. Moreover, the T allele and the TT genotype of rs2241766 were significantly more frequent in patients with poor glycemic control (P < 0.05). Individuals with the TT genotype of rs2241766 had significantly lower levels of serum adiponectin (P < 0.05). It was concluded that lower levels of serum adiponectin and the T allele of rs2241766 SNP in ADIPOQ were associated with poor glycemic control in T2DM patients.


Assuntos
Adiponectina , Diabetes Mellitus Tipo 2 , Adiponectina/genética , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Controle Glicêmico , Humanos , Polimorfismo de Nucleotídeo Único/genética
18.
Methods Mol Biol ; 2477: 349-379, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524127

RESUMO

Genome-wide transposon mutagenesis followed by deep sequencing allows the genome-wide mapping of growth-affecting loci in a straightforward and time-efficient way.SAturated Transposon Analysis in Yeast (SATAY) takes advantage of a modified maize transposon that is highly mobilizable in S. cerevisiae. SATAY allows not only the genome-wide mapping of genes required for growth in select conditions (such as genetic interactions or drug sensitivity/resistance), but also of protein sub-domains, as well as the creation of gain- and separation-of-function alleles. From strain preparation to the mapping of sequencing reads, we detail all the steps for the making and analysis of SATAY libraries in any S. cerevisiae lab, requiring only ordinary equipment and access to a Next-Gen sequencing platform.


Assuntos
Elementos de DNA Transponíveis , Saccharomyces cerevisiae , Alelos , Mapeamento Cromossômico , Elementos de DNA Transponíveis/genética , Mutagênese Insercional , Saccharomyces cerevisiae/genética
19.
Eur J Med Res ; 27(1): 65, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35526059

RESUMO

BACKGROUND: Increasing evidence shows that genetic variants of genes in the diabetes mellitus (DM) metabolic pathway, such as the vitamin D receptor (VDR) gene rs739837 polymorphism, increase the risk of DM susceptibility. However, the findings have been inconsistent. The present study was performed to evaluate the association of VDR gene rs739837 and type 2 diabetes (T2DM) or gestational diabetes mellitus (GDM) risk. METHODS: A comprehensive meta-analysis and a subgroup analysis were conducted to assess the association between VDR rs739837 and T2DM or GDM among five genetic models (dominant, recessive, homozygote heterozygote, and allele models) using a fixed or random model. RESULTS: The meta-analysis included 9 studies. In the overall analysis, the results showed that VDR rs739837 was associated with an increased risk of T2DM or GDM in the allele model (T vs. G: OR = 1.088; 95% CI: 1.018-1.163; P = 0.012) and dominant model (TT + GT vs. GG: OR = 1.095; 95% CI: 1.001-1.197; P = 0.047). In the subgroup analysis, VDR rs739837 was also associated with an increased risk of T2DM in the allele model (T vs. G: OR = 1.159; 95% CI: 1.055-1.273; P = 0.002) and dominant model (TT + GT vs. GG: OR = 1.198; 95% CI: 1.048-1.370; P = 0.008). However, VDR rs739837 was not associated with GDM. CONCLUSIONS: Significant associations were found between the VDR rs739837 polymorphism and T2DM susceptibility, but not with GDM.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Feminino , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Receptores de Calcitriol/genética
20.
Front Endocrinol (Lausanne) ; 13: 798417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399941

RESUMO

Background: Increasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two. Methods: The PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01). Conclusion: Polymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.


Assuntos
Adiponectina , Hepatopatia Gordurosa não Alcoólica , Adiponectina/genética , Alelos , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único
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