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1.
Theor Appl Genet ; 137(7): 147, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834870

RESUMO

KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.


Assuntos
Mapeamento Cromossômico , Cromossomos de Plantas , Haplótipos , Fenótipo , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Mapeamento Cromossômico/métodos , Marcadores Genéticos , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Sementes/genética , Melhoramento Vegetal , Alelos , Genes de Plantas
2.
Sci Rep ; 14(1): 12802, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834682

RESUMO

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39-2.75), and males showed an OR of 1.31 (95% CI: 1.19-1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.


Assuntos
Bancos de Espécimes Biológicos , Diabetes Mellitus Tipo 2 , Predisposição Genética para Doença , Glucosefosfato Desidrogenase , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Glucosefosfato Desidrogenase/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Deficiência de Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Fatores Sexuais , Fatores de Risco , Genótipo , Alelos
3.
Medicine (Baltimore) ; 103(23): e38333, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847697

RESUMO

The current research aims to investigate the relationship between Interleukin-17 (IL-17) polymorphism and the risk of recurrent pregnancy loss (RPL) within a Chinese population. Totally, 120 patients with RPL were selected and enrolled as the experiment group. Additionally, 210 healthy individuals undergoing routine physical examinations during the same period served as the control group. The IL-17 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism method. The IL-17 rs2275913 polymorphism exhibited 3 genotypes: GG, GA, and AA. Significant associations were observed with the AA genotype and A allele (all P < .05), indicating women with the AA genotype were 2.06 times more likely to experience RPL compared to those with the GG genotype. Similarly, women carrying the A allele faced a 1.63 times higher risk of RPL than those with the G allele. Regarding the IL-17 rs763780 polymorphism, which also presented 3 genotypes (TT, TC, CC), significant associations were noted for the CC genotype and C allele (all P < .05). Women with the CC genotype had a 1.84 times greater risk of suffering from RPL compared to those with the TT genotype, and those with the C allele were 1.51 times more likely to experience RPL than those with the T allele. The IL-17 rs2275913 and rs763780 polymorphisms contribute an increased risk to RPL in the Chinese population. Further studies, with larger sample sizes and more rigorous designs, are necessary to validate or replicate our current results.


Assuntos
Aborto Habitual , Povo Asiático , Predisposição Genética para Doença , Interleucina-17 , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Aborto Habitual/genética , Interleucina-17/genética , Adulto , Gravidez , China/epidemiologia , Povo Asiático/genética , Estudos de Casos e Controles , Genótipo , Alelos , População do Leste Asiático
4.
Sci Adv ; 10(23): eadm7452, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848363

RESUMO

Understanding CRISPR-Cas9's capacity to produce native overexpression (OX) alleles would accelerate agronomic gains achievable by gene editing. To generate OX alleles with increased RNA and protein abundance, we leveraged multiplexed CRISPR-Cas9 mutagenesis of noncoding sequences upstream of the rice PSBS1 gene. We isolated 120 gene-edited alleles with varying non-photochemical quenching (NPQ) capacity in vivo-from knockout to overexpression-using a high-throughput screening pipeline. Overexpression increased OsPsbS1 protein abundance two- to threefold, matching fold changes obtained by transgenesis. Increased PsbS protein abundance enhanced NPQ capacity and water-use efficiency. Across our resolved genetic variation, we identify the role of 5'UTR indels and inversions in driving knockout/knockdown and overexpression phenotypes, respectively. Complex structural variants, such as the 252-kb duplication/inversion generated here, evidence the potential of CRISPR-Cas9 to facilitate significant genomic changes with negligible off-target transcriptomic perturbations. Our results may inform future gene-editing strategies for hypermorphic alleles and have advanced the pursuit of gene-edited, non-transgenic rice plants with accelerated relaxation of photoprotection.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Mutagênese , Oryza , Oryza/genética , Edição de Genes/métodos , Alelos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Transgenes , Regulação da Expressão Gênica de Plantas
5.
Sci Rep ; 14(1): 13196, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851847

RESUMO

Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (- 1082 A > G, - 819 T > C and - 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both - 819 T > C and - 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by - 819 T > C and - 592 A > C variants and pharmacotherapy.


Assuntos
Síndrome Coronariana Aguda , Predisposição Genética para Doença , Interleucina-10 , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Humanos , Interleucina-10/genética , Interleucina-10/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Genótipo , Alelos , Biomarcadores/sangue , México , Leucócitos Mononucleares/metabolismo , Frequência do Gene , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
Lancet Healthy Longev ; 5(6): e422-e430, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38824957

RESUMO

BACKGROUND: The ε4 allele of the apolipoprotein E gene (APOE4) plays a role in neurodegeneration and in cardiovascular disease, but findings on its association with mortality are inconsistent. We aimed to examine the association between APOE4 and mortality, and the role of dementia in this association. METHODS: In this pooled analysis, data on White participants aged 45-90 years who underwent APOE genotyping were drawn from two population-based cohorts: the Whitehall II study (UK), which began in 1985 and is ongoing, and the Three-City study (France), initiated in 1999 and ended in 2012. In the Three-City study, vital status was ascertained through linkage to the national registry of death Institut National de la Statistique des Études économiques, and dementia was ascertained via a neuropsychological evaluation and validation of diagnoses by an independent committee of neurologists and geriatricians. In the Whitehall II study, vital status was ascertained through linkage to the UK national mortality register, and dementia cases were ascertained by linkage to three national registers. Participants with prevalent dementia at baseline and participants missing an APOE genotype were excluded from analyses. Cox regression proportional hazard models were used to examine the association of APOE4 with all-cause, cardiovascular, and cancer mortality. The role of dementia in the association between APOE4 status and mortality was examined by excluding participants who developed dementia during follow-up from the analyses. An illness-death model was then used to examine the role of incident dementia in these associations. FINDINGS: 14 091 participants (8492 from the Three-City study and 5599 from the Whitehall II study; 6668 [47%] of participants were women and 7423 [53%] were men), with a median follow-up of 15·4 years (IQR 10·6-21·2), were included in the analyses. Of these participants, APOE4 carriers (3264 [23%] of the cohort carried at least one ε4 allele) had a higher risk of all-cause mortality compared with non-carriers, with hazard ratios (HR) of 1·16 (95% CI 1·07-1·26) for heterozygotes and 1·59 (1·24-2·06) for homozygotes. Compared with APOE3 homozygotes, higher cardiovascular mortality was observed in APOE4 carriers, with a HR of 1·23 (1·01-1·50) for heterozygotes, and no association was found between APOE4 and cancer mortality. Excluding cases of incident dementia over the follow-up resulted in attenuated associations with mortality in homozygotes but not in heterozygotes. The illness-death model indicated that the higher mortality risk in APOE4 carriers was not solely attributable to dementia. INTERPRETATION: We found a robust association between APOE4 and all-cause and cardiovascular mortality but not cancer mortality. Dementia explained a significant proportion of the association with all-cause mortality for APOE4 homozygotes, while non-dementia factors, such as cardiovascular disease mortality, are likely to play a role in shaping mortality outcomes in APOE4 heterozygotes. FUNDING: National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.


Assuntos
Apolipoproteína E4 , Demência , Humanos , Feminino , Apolipoproteína E4/genética , Masculino , Idoso , Demência/genética , Demência/mortalidade , Demência/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos de Coortes , Causas de Morte , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/mortalidade , Genótipo , Reino Unido/epidemiologia , Alelos
7.
Genome Biol ; 25(1): 144, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822397

RESUMO

BACKGROUND: Variation in X chromosome inactivation (XCI) in human-induced pluripotent stem cells (hiPSCs) can impact their ability to model biological sex biases. The gene-wise landscape of X chromosome gene dosage remains unresolved in female hiPSCs. To characterize patterns of de-repression and escape from inactivation, we performed a systematic survey of allele specific expression in 165 female hiPSC lines. RESULTS: XCI erosion is non-random and primarily affects genes that escape XCI in human tissues. Individual genes and cell lines vary in the frequency and degree of de-repression. Bi-allelic expression increases gradually after modest decrease of XIST in cultures, whose loss is commonly used to mark lines with eroded XCI. We identify three clusters of female lines at different stages of XCI. Increased XCI erosion amplifies female-biased expression at hypomethylated sites and regions normally occupied by repressive histone marks, lowering male-biased differences in the X chromosome. In autosomes, erosion modifies sex differences in a dose-dependent way. Male-biased genes are enriched for hypermethylated regions, and de-repression of XIST-bound autosomal genes in female lines attenuates normal male-biased gene expression in eroded lines. XCI erosion can compensate for a dominant loss of function effect in several disease genes. CONCLUSIONS: We present a comprehensive view of X chromosome gene dosage in hiPSCs and implicate a direct mechanism for XCI erosion in regulating autosomal gene expression in trans. The uncommon and variable reactivation of X chromosome genes in female hiPSCs can provide insight into X chromosome's role in regulating gene expression and sex differences in humans.


Assuntos
Cromossomos Humanos X , Células-Tronco Pluripotentes Induzidas , RNA Longo não Codificante , Inativação do Cromossomo X , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Feminino , Cromossomos Humanos X/genética , Masculino , RNA Longo não Codificante/genética , Alelos , Regulação da Expressão Gênica , Metilação de DNA
8.
HLA ; 103(6): e15553, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837619

RESUMO

HLA-C*06:364 differs from HLA-C*06:02:01:01 by a non-synonymous nucleotide substitution in exon 3.


Assuntos
Alelos , Éxons , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Sequência de Bases , Análise de Sequência de DNA/métodos , Códon , Alinhamento de Sequência
10.
HLA ; 103(6): e15557, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837671

RESUMO

The novel KIR2DL3*00112 allele differs from the closest allele KIR2DL3*00101 by a single same sense mutation.


Assuntos
Alelos , Éxons , Receptores KIR2DL3 , Humanos , Receptores KIR2DL3/genética , Sequência de Bases , Análise de Sequência de DNA/métodos , Teste de Histocompatibilidade , Polimorfismo de Nucleotídeo Único , Mutação Puntual , Alinhamento de Sequência
11.
HLA ; 103(6): e15551, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837672

RESUMO

One nucleotide substitution in codon 130 of HLA-DQB1*03:03:02:01 results in a novel allele HLA-DQB1*03:96.


Assuntos
Alelos , Códon , Éxons , Cadeias beta de HLA-DQ , Teste de Histocompatibilidade , Humanos , Cadeias beta de HLA-DQ/genética , Taiwan , Sequência de Bases , Povo Asiático/genética , Análise de Sequência de DNA/métodos , Polimorfismo de Nucleotídeo Único
12.
HLA ; 103(6): e15509, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837741

RESUMO

Loss of heterozygosity (LOH) has been reported to occur in HLA regions in cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the details of how this is related to the progression of CIN have been unclear. In this study, we examined the human papillomavirus (HPV) antigen-presenting capacity of people with CIN and the significance of LOH of HLA class I in the progression of CIN. It was shown that differences in antigen-presenting capacity among each case depended on HLA types, not HPV genotypes. Focusing on the HLA type, there was a positive correlation between antigen-presenting capacity against HPV and the frequency of allelic loss. Furthermore, the lost HLA-B alleles had a higher HPV antigen-presenting capacity than intact alleles. In addition, frequency of LOH of HLA class I was significantly higher in advanced CIN (CIN2-3) than in cervicitis or early-stage CIN (CIN1): around half of CIN2-3 had LOH of any HLA class I. Moreover, the antigen-presenting capacity against E5, which is the HPV proteins that facilitate viral escape from this immune surveillance by suppressing HLA class I expression, had the most significant impact on the LOH in HLA-B. This study suggests that HPV evades immune surveillance mechanisms when host cells lose the capacity for antigen presentation by HLA class I molecules, resulting in long-term infection and progression to advanced lesions.


Assuntos
Antígenos de Histocompatibilidade Classe I , Perda de Heterozigosidade , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Feminino , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/genética , Apresentação de Antígeno/imunologia , Adulto , Alelos , Papillomaviridae/imunologia , Vigilância Imunológica , Pessoa de Meia-Idade , Genótipo
13.
HLA ; 103(6): e15543, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837862

RESUMO

The MHC class I region contains crucial genes for the innate and adaptive immune response, playing a key role in susceptibility to many autoimmune and infectious diseases. Genome-wide association studies have identified numerous disease-associated SNPs within this region. However, these associations do not fully capture the immune-biological relevance of specific HLA alleles. HLA imputation techniques may leverage available SNP arrays by predicting allele genotypes based on the linkage disequilibrium between SNPs and specific HLA alleles. Successful imputation requires diverse and large reference panels, especially for admixed populations. This study employed a bioinformatics approach to call SNPs and HLA alleles in multi-ethnic samples from the 1000 genomes (1KG) dataset and admixed individuals from Brazil (SABE), utilising 30X whole-genome sequencing data. Using HIBAG, we created three reference panels: 1KG (n = 2504), SABE (n = 1171), and the full model (n = 3675) encompassing all samples. In extensive cross-validation of these reference panels, the multi-ethnic 1KG reference exhibited overall superior performance than the reference with only Brazilian samples. However, the best results were achieved with the full model. Additionally, we expanded the scope of imputation by developing reference panels for non-classical, MICA, MICB and HLA-H genes, previously unavailable for multi-ethnic populations. Validation in an independent Brazilian dataset showcased the superiority of our reference panels over the Michigan Imputation Server, particularly in predicting HLA-B alleles among Brazilians. Our investigations underscored the need to enhance or adapt reference panels to encompass the target population's genetic diversity, emphasising the significance of multiethnic references for accurate imputation across different populations.


Assuntos
Alelos , Etnicidade , Frequência do Gene , Polimorfismo de Nucleotídeo Único , Humanos , Brasil , Etnicidade/genética , Antígenos HLA/genética , Desequilíbrio de Ligação , Estudo de Associação Genômica Ampla/métodos , Genótipo , Genética Populacional/métodos , Antígenos de Histocompatibilidade Classe I/genética , Biologia Computacional/métodos
15.
Mol Biol Rep ; 51(1): 714, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824264

RESUMO

BACKGROUND: NOTCH3 variants are known to be linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, some null NOTCH3 variants with homozygous inheritance cause neurological symptoms distinct from CADASIL. The aim of this study was to expand the clinical spectrum of this distinct condition and provide further evidence of its autosomal recessive inheritance. METHODS AND RESULTS: Whole exome sequencing (WES) was performed on a proband who exhibited livedo racemosa, ataxia, cognitive decline, seizures, and MRI white matter abnormalities without anterior temporal pole lesions. Segregation analysis was conducted with Sanger sequencing. WES of the proband identified a novel homozygous NOTCH3 null variant (c.2984delC). The consanguineous parents were confirmed as heterozygous variant carriers. In addition, three heterozygous NOTCH3 null variants were reported as incidental findings in three unrelated cases analyzed in our center. CONCLUSION: The findings of this study suggest an autosomal recessive inheritance pattern in this early-onset leukoencephalopathy, in contrast to CADASIL's dominant gain-of-function mechanism; which is a clear example of genotype-phenotype correlation. Comprehensive genetic analysis provides valuable insights into disease mechanisms and facilitates diagnosis and family planning for NOTCH3-associated neurological disorders.


Assuntos
Sequenciamento do Exoma , Genes Recessivos , Linhagem , Fenótipo , Receptor Notch3 , Humanos , Receptor Notch3/genética , Masculino , Feminino , Sequenciamento do Exoma/métodos , Genes Recessivos/genética , Adulto , Estudos de Associação Genética , CADASIL/genética , Imageamento por Ressonância Magnética/métodos , Alelos , Homozigoto , Consanguinidade , Mutação com Perda de Função/genética , Mutação/genética , Heterozigoto
16.
Theor Appl Genet ; 137(7): 148, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836887

RESUMO

KEY MESSAGE: Three stable QTL for grain zinc concentration were identified in wheat landrace Chinese Spring. Favorable alleles were more frequent in landraces than in modern wheat cultivars. Wheat is a major source of dietary energy for the growing world population. Developing cultivars with enriched zinc and iron can potentially alleviate human micronutrient deficiency. In this study, a recombinant inbred line (RIL) population with 245 lines derived from cross Zhou 8425B/Chinese Spring was used to detect quantitative trait loci (QTL) for grain zinc concentration (GZnC) and grain iron concentration (GFeC) across four environments. Three stable QTL for GZnC with all favorable alleles from Chinese Spring were identified on chromosomes 3BL, 5AL, and 5BL. These QTL explaining maxima of 8.7%, 5.8%, and 7.1% of phenotypic variances were validated in 125 resequenced wheat accessions encompassing both landraces and modern cultivars using six kompetitive allele specific PCR (KASP) assays. The frequencies of favorable alleles for QGZnCzc.caas-3BL, QGZnCzc.caas-5AL and QGZnCzc.caas-5BL were higher in landraces (90.4%, 68.0%, and 100.0%, respectively) compared to modern cultivars (45.9%, 35.4%, and 40.9%), suggesting they were not selected in breeding programs. Candidate gene association studies on GZnC in the cultivar panel further delimited the QTL into 8.5 Mb, 4.1 Mb, and 47.8 Mb regions containing 46, 4, and 199 candidate genes, respectively. The 5BL QTL located in a region where recombination was suppressed. Two stable and three less stable QTL for GFeC with favorable alleles also from Chinese Spring were identified on chromosomes 4BS (Rht-B1a), 4DS (Rht-D1a), 1DS, 3AS, and 6DS. This study sheds light on the genetic basis of GZnC and GFeC in Chinese Spring and provides useful molecular markers for wheat biofortification.


Assuntos
Alelos , Mapeamento Cromossômico , Ferro , Fenótipo , Locos de Características Quantitativas , Triticum , Zinco , Triticum/genética , Zinco/metabolismo , Ferro/metabolismo , Grão Comestível/genética , Cromossomos de Plantas/genética , Sementes/genética , Sementes/química , Genótipo
17.
Technol Cancer Res Treat ; 23: 15330338241246457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836311

RESUMO

Objectives: Exploring the relationship between the hOGG1 rs1052133 polymorphism and the occurrence of nasopharyngeal carcinoma (NPC). Methods: PubMed, Web of Science, Scopus, CNKI, Wanfangdata, and VIP were used to search for studies and the NOS evaluation scale was used to evaluate the quality. All studies were grouped according to different genotypes. The Cochrane's Q test and I2 test were used for heterogeneity evaluations. If heterogeneity was small, the fixed effects model was used, and conversely, the random effects model was used. Publication bias was also detected. P < .05 in all results indicated statistically significant. Results: We ultimately included 6 studies with 2021 NPC patients in the study group and 2375 healthy populations in the control group. After meta-analysis, it was found that the total OR value of the "Ser/Cys (CG) vs Ser/Ser (CC)" group was 1.00 (95% CI: 0.85-1.18) and the "Cys/Cys (GG) vs Ser/Ser (CC)" group was 1.06 (95% CI: 0.87-1.28). These results were not statistically significant (P > .05). Furthermore, the integrated total OR values of each group were not statistically significant with or without the smoking history, even in other genotype models (Allele, Dominant, Recessive, and Additive) (P > .05). Conclusion: There is no clear correlation between the hOGG1 rs1052133 polymorphism and the occurrence of NPC, even with or without the smoking history.


Assuntos
Alelos , DNA Glicosilases , Predisposição Genética para Doença , Genótipo , Carcinoma Nasofaríngeo , Polimorfismo de Nucleotídeo Único , Humanos , Carcinoma Nasofaríngeo/genética , DNA Glicosilases/genética , Neoplasias Nasofaríngeas/genética , Razão de Chances , Estudos de Associação Genética , Viés de Publicação , Estudos de Casos e Controles
18.
Front Immunol ; 15: 1384823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840925

RESUMO

Objective: In a cooperative study of the University Hospital Leipzig, University of Leipzig, and the Charité Berlin on kidney transplant patients, we analysed the occurrence of HLA-specific antibodies with respect to the HLA setup of the patients. We aimed at the definition of specific HLA antigens towards which the patients produced these antibodies. Methods: Patients were typed for the relevant HLA determinants using mainly the next-generation technology. Antibody screening was performed by the state-of-the-art multiplex-based technology using microspheres coupled with the respective HLA alleles of HLA class I and II determinants. Results: Patients homozygous for HLA-A*02, HLA-A*03, HLA-A*24, HLA-B*07, HLA-B*18, HLA-B*35, HLA-B*44, HLA-C*03, HLA-C*04, and HLA-C*07 in the class I group and HLA-DRB1*01, HLA-DRB1*03, HLA-DRB1*07, HLA-DRB1*15, HLA-DQA1*01, HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*03(7), HLA-DQB1*06, HLA-DPA1*01, and HLA-DPB1*04 in the class II group were found to have a significant higher antibody production compared to the heterozygous ones. In general, all HLA determinants are affected. Remarkably, HLA-A*24 homozygous patients can produce antibodies towards all HLA-A determinants, while HLA-B*18 homozygous ones make antibodies towards all HLA-B and selected HLA-A and C antigens, and are associated with an elevation of HLA-DRB1, parts of DQB1 and DPB1 alleles. Homozygosity for the HLA class II HLA-DRB1*01, and HLA-DRB1*15 seems to increase the risk for antibody responses against most of the HLA class I antigens (HLA-A, HLA-B, and HLA-C) in contrast to HLA-DQB1*03(7) where a lower risk towards few HLA-A and HLA-B alleles is found. The widely observed differential antibody response is therefore to be accounted to the patient's HLA type. Conclusion: Homozygous patients are at risk of producing HLA-specific antibodies hampering the outcome of transplantation. Including this information on the allocation procedure might reduce antibody-mediated immune reactivity and prevent graft loss in a patient at risk, increasing the life span of the transplanted organ.


Assuntos
Antígenos HLA , Homozigoto , Isoanticorpos , Transplante de Rim , Humanos , Fatores de Risco , Antígenos HLA/genética , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Teste de Histocompatibilidade , Alelos , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Masculino , Feminino
19.
PLoS One ; 19(6): e0302643, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38829901

RESUMO

BACKGROUND: The A allele of rs373863828 in CREB3 regulatory factor is associated with high Body Mass Index, but lower odds of type 2 diabetes. These associations have been replicated elsewhere, but to date all studies have been cross-sectional. Our aims were (1) to describe the development of type 2 diabetes and change in fasting glucose between 2010 and 2018 among a longitudinal cohort of adult Samoans without type 2 diabetes or who were not using diabetes medications at baseline, and (2) to examine associations between fasting glucose rate-of-change (mmol/L per year) and the A allele of rs373863828. METHODS: We describe and test differences in fasting glucose, the development of type 2 diabetes, body mass index, age, smoking status, physical activity, urbanicity of residence, and household asset scores between 2010 and 2018 among a cohort of n = 401 adult Samoans, selected to have a ~2:2:1 ratio of GG:AG: AA rs373863828 genotypes. Multivariate linear regression was used to test whether fasting glucose rate-of-change was associated with rs373863828 genotype, and other baseline variables. RESULTS: By 2018, fasting glucose and BMI significantly increased among all genotype groups, and a substantial portion of the sample developed type 2 diabetes mellitus. The A allele was associated with a lower fasting glucose rate-of-change (ß = -0.05 mmol/L/year per allele, p = 0.058 among women; ß = -0.004 mmol/L/year per allele, p = 0.863 among men), after accounting for baseline variables. Mean fasting glucose and mean BMI increased over an eight-year period and a substantial number of individuals developed type 2 diabetes by 2018. However, fasting glucose rate-of-change, and type 2 diabetes development was lower among females with AG and AA genotypes. CONCLUSIONS: Further research is needed to understand the effect of the A allele on fasting glucose and type 2 diabetes development. Based on our observations that other risk factors increased over time, we advocate for the continued promotion for diabetes prevention and treatment programming, and the reduction of modifiable risk factors, in this setting.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Jejum , Humanos , Feminino , Diabetes Mellitus Tipo 2/genética , Masculino , Pessoa de Meia-Idade , Glicemia/metabolismo , Adulto , Jejum/sangue , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Alelos , Samoa , Estudos de Coortes , Índice de Massa Corporal , Genótipo , Estudos Longitudinais , Estudos Transversais , Idoso , Proteínas Supressoras de Tumor
20.
BMC Genom Data ; 25(1): 50, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831280

RESUMO

BACKGROUND: Dental caries (DC) is a multifaceted oral condition influenced by genetic and environmental factors. Recent advancements in genotyping and sequencing technologies, such as Genome-Wide Association Studies (GWAS) have helped researchers to identify numerous genetic variants associated with DC, but their prevalence and significance across diverse global populations remain poorly understood as most of the studies were conducted in European populations, and very few were conducted in Asians specifically in Indians. AIM: This study aimed to evaluate the genetic affinity of effect alleles associated with DC to understand the genetic relationship between global populations with respect to the Indian context. METHODOLOGY: This present study used an empirical approach in which variants associated with DC susceptibility were selected. These variants were identified and annotated using the GWAS summary. The genetic affinity was evaluated using Fst. RESULTS: The effect of allele frequencies among different populations was examined, revealing variations in allele distribution. African populations exhibited higher frequencies of specific risk alleles, whereas East Asian and European populations displayed distinct profiles. South Asian populations showed a unique genetic cluster. CONCLUSION: Our study emphasises the complex genetic landscape of DC and highlights the need for population-specific research as well as validation of GWAS-identified markers in Indians before defining them as established candidate genes.


Assuntos
Cárie Dentária , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Cárie Dentária/genética , Cárie Dentária/epidemiologia , Predisposição Genética para Doença , Alelos , Polimorfismo de Nucleotídeo Único , Índia/epidemiologia , Índia/etnologia , Povo Asiático/genética
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