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1.
Gene ; 766: 145143, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32911028

RESUMEN

We aimed to test the hypothesis that apelin (APLN) and its receptor AGTRL1 (APLNR) genes may contribute to the pathogenesis of myocardial infarction in Han Chinese. This is a hospital-based, case-control association study, involving 1067 patients with myocardial infarction and 942 healthy controls. Myocardial infarction is diagnosed by electrocardiogram or anatomopathological examination. Eight polymorphisms in APLN gene and 5 in APLNR gene were genotyped using the TaqMan assay. Risk was summarized as odds ratio (OR) and 95% confidence interval (CI). In males, rs56204867-G allele (adjusted OR, 95% CI, p: 0.21, 0.08-0.55, 0.002) and rs2235309-T allele (0.60, 0.42-0.84, 0.004) was associated with a significantly reduced risk of myocardial infarction, and the mutations of rs2235310 was associated with an increased risk (1.41, 1.06-2.52, 0.021), as well as for rs948847-GG genotype (1.85, 1.23-2.91, 0.007). In females, the presence of rs56204867-AG and -GG genotypes was significantly associated with 44% and 50% reduced risk (0.56 and 0.50, 0.40-8.04 and 0.29-0.86, 0.007 and 0.036), respectively; for rs2235310, CC genotype was associated with 72% increased risk (1.72, 1.09-3.22, 0.016), and the odds of myocardial infarction was 3.47 for rs9943582-TT genotype (95% CI: 1.53-7.57, 0.009). The gender-specific association of APLN and APLNR genes with myocardial infarction was reinforced by further linkage and haplotype analyses. Finally, nomograms based on significant polymorphisms are satisfactory, with the C-indexes over 80% for both genders. Taken together, our findings indicate that APLN and APLNR genes are potential candidates in the pathogenesis of myocardial infarction in Han Chinese, and importantly their contribution is gender-dependent.


Asunto(s)
Receptores de Apelina/genética , Apelina/genética , Grupo de Ascendencia Continental Asiática/genética , Predisposición Genética a la Enfermedad/genética , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad
2.
Gene ; 766: 145132, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32911029

RESUMEN

Dysfunctions in mechanisms of gene regulation based on RNA interference are recognized as a common feature of the molecular basis of cancer pathogenesis. Therefore, as one of the crucial components of the machinery involved in the biogenesis of both siRNAs and microRNA molecules, DICER was recognized as one of the candidates for the research in the field of carcinogenesis. Due to their potential functional properties, several genetic variants located within DICER1 gene were analyzed for their possible association with the susceptibility to cancer through case-control studies. In order to elucidate their effect on the overall cancer risk, we conducted an updated meta-analysis of all eligible association studies. The publications were selected based on PubMed database search, while OpenMeta-analyst and MetaGenyo software were used for quantitative data synthesis. Statistically significant results were found for the association of rs1057035 with the overall cancer risk under multiple genetic models (PCT vs. TT < 0.001, ORCT vs. TT = 0.870, 95% CI = 0.812-0.933; Pallelic = 0.009, ORallelic = 0.896, 95% CI = 0.825-0.973; Pdom < 0.001, ORdom = 0.874, 95% CI = 0.817-0.934; Poverdom = 0.004, ORoverdom = 0.858, 95% CI = 0.773-0.953). Other selected genetic variants within DICER1, rs13078, rs1209904 and rs3742330, did not show the association with the overall susceptibility to malignant diseases. We conclude that rs1057035 may represent a potential biomarker associated with the risk of developing cancer, which requires a confirmation in a larger set of studies.


Asunto(s)
ARN Helicasas DEAD-box/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética , Ribonucleasa III/genética , Alelos , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Estudios de Asociación Genética , Genotipo , Humanos , MicroARNs/genética , Riesgo
3.
Gene ; 766: 145092, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32916247

RESUMEN

Cigarette smoking is a major lifestyle factor leading to different human diseases. The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA. Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes. Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients. Four TDG SNPs-rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population. The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (>5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers. Also, in smokers aged less than 29 years, the "CT," "TT," and "CT + TT" alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6, 4, and 5 times, respectively, in contrast with the ancestral "CC" homozygous allele. A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities. Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population. In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene. This variation on TDG SNP's with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Fumar/genética , Timina ADN Glicosilasa/genética , Adulto , Alelos , Grupos Étnicos/genética , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino
4.
Gene ; 766: 145127, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32937184

RESUMEN

Telomeres are duplex tandem repeats of DNA sequence 5'-TTAGGG-3' at chromosomal ends synthesized by telomerase enzyme (TE). Telomeres length (TL) shortening is associated with age and age-related disorders. Recently, we demonstrated marked leukocytes TL (LTL) shortening in T2DM. To set the relationship between the TE, LTL and T2DM, we analyzed samples from 212 Kuwaiti subjects, 112 patients withT2DM and 100 non-diabetic subjects. The plasma TE and fasting insulin were measured by ELISA, the LTL was estimated by qPCR and three SNPs of genes related to TL; TERC rs12696304 (C/G), TERT rs2736100 (C/A) and ACYP2 rs6713088 (C/G) were genotyped by rtPCR. Results revealed comparable TE levels and alleles/genotypes between the cases and controls with no influence of either on the LTL. Interestingly, although the plasma concentration of the TE was generally low, it was significantly influenced by the TERT and ACYP2 but not TERC polymorphisms. The CC genotype carriers of rs2736100 (C/A) had significantly higher plasma TE levels compared to CA and AA carriers, p 0.009 and p 0.047, respectively, and the A-allele was associated with low TE, p 0.018. Similarly, significantly higher TE levels were detected in CC carriers of ACYP2 rs6713088 (C/G) compared with GC carriers, p 0.002, and the G-allele was associated with low TE, p 0.009. Finally, the TERT and ACYP2 polymorphisms had an influence on blood glucose levels. In conclusion, the telomeres shortening in T2DM was not due to TE deficiency or gene polymorphisms, while the TE levels were significantly associated with the TERT and ACYP2 but not TERC polymorphisms.


Asunto(s)
Ácido Anhídrido Hidrolasas/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleótido Simple/genética , ARN/genética , Telomerasa/genética , Acortamiento del Telómero/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Telomerasa/sangre
5.
Eur J Endocrinol ; 183(6): K7-K12, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33105102

RESUMEN

A monoallelic germline alteration of ARMC5 causes primary bilateral macronodular adrenal hyperplasia (PBMAH) with Cushing's syndrome via its subsequent somatic alteration on the other allele as the second hit. PBMAH is sometimes complicated with meningioma. Dependency of such a multi-organ disease on the second hit mechanism was reported before, but this finding has not been confirmed yet. We describe a case of a 65-year-old female with PBMAH, carrying a heterozygous germline alteration of ARMC5, p.R267*, complicated with meningioma associated with somatic loss of heterozygosity (LOH) of the unaffected allele. Pathogenic alterations of ARMC5 may also contribute to the development of meningioma by the two-hit mechanism.


Asunto(s)
Proteínas del Dominio Armadillo/genética , Síndrome de Cushing/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Anciano , Alelos , Femenino , Mutación de Línea Germinal/genética , Humanos , Pérdida de Heterocigocidad/genética
6.
BMC Bioinformatics ; 21(1): 441, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-33028201

RESUMEN

BACKGROUND: Inferring phylogenetic relationships of polyploid species and their diploid ancestors (leading to reticulate phylogenies in the case of an allopolyploid origin) based on multi-locus sequence data is complicated by the unknown assignment of alleles found in polyploids to diploid subgenomes. A parsimony-based approach to this problem has been proposed by Oberprieler et al. (Methods Ecol Evol 8:835-849, 2017), however, its implementation is of limited practical value. In addition to previously identified shortcomings, it has been found that in some cases, the obtained results barely satisfy the applied criterion. To be of better use to other researchers, a reimplementation with methodological refinement appears to be indispensable. RESULTS: We present the AllCoPol package, which provides a heuristic method for assigning alleles from polyploids to diploid subgenomes based on the Minimizing Deep Coalescences (MDC) criterion in multi-locus sequence datasets. An additional consensus approach further allows to assess the confidence of phylogenetic reconstructions. Simulations of tetra- and hexaploids show that under simplifying assumptions such as completely disomic inheritance, the topological errors of reconstructed phylogenies are similar to those of MDC species trees based on the true allele partition. CONCLUSIONS: AllCoPol is a Python package for phylogenetic reconstructions of polyploids offering enhanced functionality as well as improved usability. The included methods are supplied as command line tools without the need for prior programming knowledge.


Asunto(s)
Interfaz Usuario-Computador , Alelos , Bases de Datos Genéticas , Leucanthemum/clasificación , Leucanthemum/genética , Tipificación de Secuencias Multilocus , Filogenia , Poliploidía
7.
BMC Med Genet ; 21(1): 198, 2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-33036569

RESUMEN

BACKGROUND: Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations. METHODS: All studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay. RESULTS: The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G > A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects. CONCLUSION: The FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).


Asunto(s)
Factor V/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Protrombina/genética , Trombofilia/genética , Adolescente , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Trombofilia/diagnóstico , Adulto Joven
8.
BMC Med Genet ; 21(1): 201, 2020 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-33046033

RESUMEN

BACKGROUND: CDKN2A hypermethylation is among the major events associated with carcinogenesis and is also observed in non-neoplastic colonic mucosa in patients with ulcerative colitis (UC). Macrophage migration inhibitory factor (MIF) plays a crucial role in promoting gastrointestinal inflammation characteristic of UC. The aim of this study is to explore associations between CDKN2A methylation status and MIF polymorphisms (rs755622 and rs5844572). METHODS: One hundred and fifty-nine patients diagnosed with UC were enrolled in this study. The methylation status of p14ARF and p16INK4a was determined by MSP; MIF genotypes were identified by PCR-SSCP. RESULTS: We found no differences with respect to mean age, gender, clinical type (chronic continuous or relapse/remitting), or extent of disease among the patients with methylated and unmethylated p14ARF or p16INK4a. Carrying the rs755622 C allele indicated a significantly higher risk for p14ARF methylation (odds ratio (OR), 2.16; 95% confidence interval (CI), 1.08-4.32; p = 0.030); similarly, carrying the rs5844572 7-repeat allele indicated a significantly higher risk for p16INK4a methylation (OR, 2.57; 95% CI, 1.26-5.24; p = 0.0094) after an adjusted regression analysis. The carriers of the rs755662 C allele or the rs5844572 7-repeat allele were both at a significantly higher risk for methylation of both p14ARF and p16INK4a when compared to the cohort in which neither of the genes were methylated (OR, 2.70; 95% CI, 1.22-6.01; p = 0.015 and OR, 2.87; 95% CI, 1.25-6.62; p = 0.013, respectively). Additionally, carrying rs755622 C allele was significantly associated with CIHM in chronic continuous of clinical type and total colitis (OR, 25.9; 95% CI, 2.55-262.6; p = 0.0059 and OR, 4.38; 95% CI, 1.12-17.2; p = 0.034, respectively), and carrying 7-repeat allele of rs5844572 was significantly associated in chronic continuous type (OR, 14.5; 95%CI, 1.46-144.3; p = 0.022). CONCLUSIONS: Taken together, our findings suggest that MIF genotypes associated with inflammation may also be involved in promoting carcinogenesis via CDKN2A hypermethylation in patients diagnosed with UC.


Asunto(s)
Colitis Ulcerosa/genética , Islas de CpG/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Metilación de ADN , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Colitis Ulcerosa/diagnóstico , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
9.
BMC Med Genet ; 21(1): 204, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-33059653

RESUMEN

BACKGROUND: Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset. METHODS: Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals. RESULTS: Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae. CONCLUSIONS: This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.


Asunto(s)
Enfermedad de Crohn/genética , Heces/microbiología , Firmicutes/fisiología , Predisposición Genética a la Enfermedad/genética , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Alelos , Niño , Estudios de Cohortes , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/microbiología , Familia , Femenino , Firmicutes/clasificación , Firmicutes/genética , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Microbiota/genética , Microbiota/fisiología , Adulto Joven
10.
Nat Commun ; 11(1): 5219, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-33060584

RESUMEN

Nitrogen (N) is a macronutrient that boosts carbon (C) metabolism and plant growth leading to biomass accumulation. The molecular connection between nitrogen utilization efficiency (NUE) and biomass production remains unclear. Here, via quantitative trait loci analysis and map-based cloning, we reveal that natural variation at the MYB61 locus leads to differences in N use and cellulose biogenesis between indica and japonica subspecies of rice. MYB61, a transcriptional factor that regulates cellulose synthesis, is directly regulated by a known NUE regulator GROWTH-REGULATING FACTOR4 (GRF4), which coordinates cellulosic biomass production and N utilization. The variation at MYB61 has been selected during indica and japonica domestication. The indica allele of MYB61 displays robust transcription resulting in higher NUE and increased grain yield at reduced N supply than that of japonica. Our study hence unravels how C metabolism is linked to N uptake and may provide an opportunity to reduce N use for sustainable agriculture.


Asunto(s)
Nitrógeno/metabolismo , Oryza/crecimiento & desarrollo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Alelos , Biomasa , Celulosa/biosíntesis , Grano Comestible/genética , Grano Comestible/metabolismo , Regulación de la Expresión Génica de las Plantas , Variación Genética , Desarrollo de la Planta , Sitios de Carácter Cuantitativo , Transducción de Señal , Transcripción Genética
11.
BMC Med Genet ; 21(1): 205, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-33066747

RESUMEN

BACKGROUND: CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa. METHODS: We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/µL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis. RESULTS: The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM. CONCLUSIONS: Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.


Asunto(s)
Islas de CpG/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN , Mucosa Gástrica/metabolismo , Polimorfismo de Nucleótido Simple , Anciano , Alelos , Antígenos CD/genética , Cadherinas/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Proteínas Quinasas Asociadas a Muerte Celular/genética , Femenino , Mucosa Gástrica/microbiología , Frecuencia de los Genes , Genotipo , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/fisiología , Humanos , Masculino , Persona de Mediana Edad
12.
BMC Med Genet ; 21(1): 206, 2020 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-33076844

RESUMEN

BACKGROUND: The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. METHODS: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. RESULTS: Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02-1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01-1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97-1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). CONCLUSIONS: This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.


Asunto(s)
Sustitución de Aminoácidos , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Proteína p53 Supresora de Tumor/genética , Alelos , Neoplasias de la Mama/diagnóstico , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Factores de Riesgo
13.
Nat Commun ; 11(1): 5346, 2020 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-33093471

RESUMEN

The mechanism that creates vitreous endosperm in the mature maize kernel is poorly understood. We identified Vitreous endosperm 1 (Ven1) as a major QTL influencing this process. Ven1 encodes ß-carotene hydroxylase 3, an enzyme that modulates carotenoid composition in the amyloplast envelope. The A619 inbred contains a nonfunctional Ven1 allele, leading to a decrease in polar and an increase in non-polar carotenoids in the amyloplast. Coincidently, the stability of amyloplast membranes is increased during kernel desiccation. The lipid composition in endosperm cells in A619 is altered, giving rise to a persistent amyloplast envelope. These changes impede the gathering of protein bodies and prevent them from interacting with starch grains, creating air spaces that cause an opaque kernel phenotype. Genetic modifiers were identified that alter the effect of Ven1A619, while maintaining a high ß-carotene level. These studies provide insight for breeding vitreous kernel varieties and high vitamin A content in maize.


Asunto(s)
Carotenoides/metabolismo , Zea mays/metabolismo , Alelos , Mapeo Cromosómico , Cruzamientos Genéticos , Endospermo/genética , Endospermo/metabolismo , Endospermo/ultraestructura , Genes de Plantas , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Fenotipo , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plastidios/genética , Plastidios/metabolismo , Plastidios/ultraestructura , Sitios de Carácter Cuantitativo , Semillas/genética , Semillas/metabolismo , Semillas/ultraestructura , Zea mays/genética , Zea mays/ultraestructura
14.
Nat Commun ; 11(1): 5238, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-33067439

RESUMEN

In heterozygous genomes, allele-specific measurements can reveal biologically significant differences in DNA methylation between homologous alleles associated with local changes in genetic sequence. Current approaches for detecting such events from whole-genome bisulfite sequencing (WGBS) data perform statistically independent marginal analysis at individual cytosine-phosphate-guanine (CpG) sites, thus ignoring correlations in the methylation state, or carry-out a joint statistical analysis of methylation patterns at four CpG sites producing unreliable statistical evidence. Here, we employ the one-dimensional Ising model of statistical physics and develop a method for detecting allele-specific methylation (ASM) events within segments of DNA containing clusters of linked single-nucleotide polymorphisms (SNPs), called haplotypes. Comparisons with existing approaches using simulated and real WGBS data show that our method provides an improved fit to data, especially when considering large haplotypes. Importantly, the method employs robust hypothesis testing for detecting statistically significant imbalances in mean methylation level and methylation entropy, as well as for identifying haplotypes for which the genetic variant carries significant information about the methylation state. As such, our ASM analysis approach can potentially lead to biological discoveries with important implications for the genetics of complex human diseases.


Asunto(s)
Metilación de ADN , Enfermedad/genética , Alelos , Islas de CpG , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple , Especificidad de la Especie , Secuenciación Completa del Genoma
15.
Medicine (Baltimore) ; 99(40): e22614, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019481

RESUMEN

BACKGROUND: The relationship between MTHFR (5, 10-methylene tetrahydrofolate reductase) gene polymorphisms and Systemic Lupus Erythematosus (SLE) has been wildly studied, but the results are still conflicting. Therefore, the purpose of this meta and pooled analysis was to identify the role of the MTHFR SNP (single nucleotide polymorphism, rs1801133) in SLE in a large sample of subjects and to assess the risk of SLE. METHODS: Data were collected from EMBASE, PubMed and China National Knowledge Infrastructure from inception to August, 2019. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the association. Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: We identified seven eligible studies involving 882 cases and 991 controls. MTHFR rs1801133 T carrier was significantly associated with increased risk of SLE when comparing to C allele [ORs were 1.766 (1.014-3.075) for T carrier vs CC, P = .04]. Furthermore, the results of the subgroup analysis by genotyping methods suggested that T allele significantly contributed to the risk of SLE for both by polymerase chain reaction-TaqMan (PCR-TaqMan) [10.111 (2.634-38.813) for TT vs CC, 3.467 (1.324-9.078) for CT vs CC and 3.744 (1.143-12.264) for TT vs C carrier]. Also the results of the subgroup analysis by ethnicity suggested that T allele significantly contributed to the risk of SLE for Asians [9.679 (4.444-21.082) for TT vs CC, 5.866 (3.021-11.389) for T carrier vs CC and 8.052 (3.861-16.795) for TT vs C carrier]. CONCLUSION: This cumulative meta-analysis showed that the MTHFR SNP (rs1801133) contributed to susceptibility of SLE. However, more multicentre well-designed case-control studies and larger sample sizes are exceedingly required to validate our findings in the future.


Asunto(s)
Lupus Eritematoso Sistémico/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple/genética , Alelos , Grupo de Ascendencia Continental Asiática/genética , Portador Sano , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Lupus Eritematoso Sistémico/etnología , Masculino , Medición de Riesgo , Sensibilidad y Especificidad
16.
Wiad Lek ; 73(8): 1637-1640, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33055325

RESUMEN

OBJECTIVE: The aim: To examine the association between polymorphisms of the IL-6 gene promoter and HF in patients with CAD and obesity. PATIENTS AND METHODS: Material and methods: 222 patients with coronary artery disease and obesity were identified. Comparison group consisted of 115 patients with coronary artery disease with normal body weight. The groups were comparable in age and sex. The exclusion group consisted of patients with severe concomitant diseases of the respiratory and digestive organs, kidneys and people with cancer. One single nucleotide polymorphisms in the interleukin-6 promoter region was analyzed. Odds ratio (OR) and 95 % confident interval (95 % CI) were calculated. RESULTS: Results: The combined course of coronary artery disease and obesity was characterized by the detection of allele C in 62 patients (27.93 %), allele G - in 160 patients (72.07 %), and genotypes CC, CG and GG - at 24 (10.81 %), 67 (30.18 %) and 131 (59.01 %) patients respectively. The results showed that the -174G allele and GG genotype in patients with coronary artery disease and obesity were associated with heart failure (OR = 2.55, 95% CI = [1.72-3.79], χ2 = 22.8; p<0.05) and (OR = 11.95, 95% CI = [3.41-41.91], χ2 = 22.5; p<0.05), whereas allele C-174 was associated with a decrease in the risk of heart failure (OR = 0.39, 95% CI = [0.26-0.58 ], χ2 = 22.75, p<0.05). CONCLUSION: Conclusions: The obtained results testify that the -174G>C polymorphism in the interleukin-6 gene is significantly associated with increased risk of heart failure in patients with coronary artery disease and obesity.


Asunto(s)
Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Interleucina-6 , Obesidad , Alelos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/genética , Femenino , Insuficiencia Cardíaca/genética , Humanos , Interleucina-6/genética , Masculino , Obesidad/complicaciones , Obesidad/genética
17.
BMC Infect Dis ; 20(1): 750, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33050903

RESUMEN

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia. METHODS: MTBC isolates (N = 156) were genetically analyzed using spacer oligotyping (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing. Major lineages and lineages were identified using MTBC databases. Logistic regression was used to correlate patient characteristics with strain clustering. RESULTS: The study identified Euro-American (EA), East-African-Indian (EAI), Indo-Oceanic (IO), Lineage_7/Aethiops vertus, Mycobacterium bovis and Mycobacterium africanum major lineages in proportions of 67.3% (105/156), 22.4% (35/156), 6.4% (10/156), 1.9% (3/156), 1.3% (2/156) and 0.6% (1/156), respectively. Lineages identified were Delhi/CAS 23.9% (37/155), Ethiopia_2 20.6% (32/155), Haarlem 14.2% (22/155), URAL 14.2%(22/155), Ethiopia_3 8.4% (13/155), TUR 6.5% (10/155), Lineage_7/Aethiops vertus 1.9% (3/155), Bovis 1.3% (2/155), LAM 1.3% (2/155), EAI 0.6% (1/155), X 0.6% (1/155) and Ethiopia H37Rv-like strain 0.6% (1/155). Of the genotyped isolates 5.8% (9/155) remained unassigned. The recent transmission index (RTI) was 3.9%. Orphan strains compared to shared types (AOR: 0.09, 95% CI: 0.04-0.25) were associated with reduced odds of clustering. The dominant TB lineage in pastoral areas was EAI and in non-pastoral areas was EA. CONCLUSION: The epidemiological data, highly diverse MTBC strains and a low RTI in South Omo, provide information contributing to the TB Control Program of the country.


Asunto(s)
Variación Genética , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Etiopía/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Epidemiología Molecular , Reacción en Cadena de la Polimerasa Multiplex , Mycobacterium bovis/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Tuberculosis Pulmonar/microbiología , Adulto Joven
18.
Front Immunol ; 11: 2008, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33013857

RESUMEN

Coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, is already responsible for more than 4.3 million confirmed cases and 295,000 deaths worldwide as of May 15, 2020. Ongoing efforts to control the pandemic include the development of peptide-based vaccines and diagnostic tests. In these approaches, HLA allelic diversity plays a crucial role. Despite its importance, current knowledge of HLA allele frequencies in South America is very limited. In this study, we have performed a literature review of datasets reporting HLA frequencies of South American populations, available in scientific literature and/or in the Allele Frequency Net Database. This allowed us to enrich the current scenario with more than 12.8 million data points. As a result, we are presenting updated HLA allelic frequencies based on country, including 91 alleles that were previously thought to have frequencies either under 5% or of an unknown value. Using alleles with an updated frequency of at least ≥5% in any South American country, we predicted epitopes in SARS-CoV-2 proteins using NetMHCpan (I and II) and MHC flurry. Then, the best predicted epitopes (class-I and -II) were selected based on their binding to South American alleles (Coverage Score). Class II predicted epitopes were also filtered based on their three-dimensional exposure. We obtained 14 class-I and four class-II candidate epitopes with experimental evidence (reported in the Immune Epitope Database and Analysis Resource), having good coverage scores for South America. Additionally, we are presenting 13 HLA-I and 30 HLA-II novel candidate epitopes without experimental evidence, including 16 class-II candidates in highly exposed conserved areas of the NTD and RBD regions of the Spike protein. These novel candidates have even better coverage scores for South America than those with experimental evidence. Finally, we show that recent similar studies presenting candidate epitopes also predicted some of our candidates but discarded them in the selection process, resulting in candidates with suboptimal coverage for South America. In conclusion, the candidate epitopes presented provide valuable information for the development of epitope-based strategies against SARS-CoV-2, such as peptide vaccines and diagnostic tests. Additionally, the updated HLA allelic frequencies provide a better representation of South America and may impact different immunogenetic studies.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Epítopos de Linfocito T/inmunología , Frecuencia de los Genes , Antígenos HLA/genética , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Proteínas del Envoltorio Viral/inmunología , Alelos , Secuencia de Aminoácidos , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Variación Genética , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/virología , América del Sur/epidemiología , Vacunas de Subunidad/inmunología , Vacunas Virales/inmunología
19.
Nat Commun ; 11(1): 5020, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33024118

RESUMEN

Lignin causes lignocellulosic biomass recalcitrance to enzymatic hydrolysis. Engineered low-lignin plants have reduced recalcitrance but often exhibit yield penalties, offsetting their gains in fermentable sugar yield. Here, CRISPR/Cas9-generated CCR2(-/*) line 12 poplars have one knockout CCR2 allele while the other contains a 3-bp deletion, resulting in a 114I115A-to-114T conversion in the corresponding protein. Despite having 10% less lignin, CCR2(-/*) line 12 grows normally. On a plant basis, the saccharification efficiency of CCR2(-/*) line 12 is increased by 25-41%, depending on the pretreatment. Analysis of monoallelic CCR2 knockout lines shows that the reduced lignin amount in CCR2(-/*) line 12 is due to the combination of a null and the specific haploinsufficient CCR2 allele. Analysis of another CCR2(-/*) line shows that depending on the specific CCR2 amino-acid change, lignin amount and growth can be affected to different extents. Our findings open up new possibilities for stably fine-tuning residual gene function in planta.


Asunto(s)
Aldehído Oxidorreductasas/genética , Lignina/metabolismo , Populus/genética , Populus/metabolismo , Aldehído Oxidorreductasas/metabolismo , Alelos , Técnicas de Inactivación de Genes , Haploinsuficiencia , Lignina/genética , Mutación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Populus/crecimiento & desarrollo , Xilema/metabolismo , Xilema/ultraestructura
20.
BMC Bioinformatics ; 21(1): 451, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33045983

RESUMEN

BACKGROUND: DNA methylation is an important epigenetic modification that plays a critical role in most eukaryotic organisms. Parental alleles in haploid genomes may exhibit different methylation patterns, which can lead to different phenotypes and even different therapeutic and drug responses to diseases. However, to our knowledge, no software is available for the identification of DNA methylation haplotype regions with combined allele-specific DNA methylation, single nucleotide polymorphisms (SNPs) and high-throughput chromosome conformation capture (Hi-C) data. RESULTS: In this paper, we developed a new method, MethHaplo, that identify DNA methylation haplotype regions with allele-specific DNA methylation and SNPs from whole-genome bisulfite sequencing (WGBS) data. Our results showed that methylation haplotype regions were ten times longer than haplotypes with SNPs only. When we integrate WGBS and Hi-C data, MethHaplo could call even longer haplotypes. CONCLUSIONS: This study illustrates the usefulness of methylation haplotypes. By constructing methylation haplotypes for various cell lines, we provide a clearer picture of the effect of DNA methylation on gene expression, histone modification and three-dimensional chromosome structure at the haplotype level. Our method could benefit the study of parental inheritance-related disease and hybrid vigor in agriculture.


Asunto(s)
Alelos , Metilación de ADN , Haplotipos/genética , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma , Epigénesis Genética , Programas Informáticos
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