General Formulas for Calculating Commonly Used Kinship Index / 法医学杂志

OBJECTIVES@#To derive general formulas for calculating commonly used kinship index (KI).@*METHODS@#By introducing the Kronecker symbol, the formulas used to calculate the same KI under different genotype combinations were summarized into a unified expression.@*RESULTS@#The general formulas were successfully derived for KI in various case situations, including the paternity index, full sibling index, half sibling index, avuncular index, grandpaternity index, first-cousin index, and second-cousin index between two individuals without or with the mother being involved; grandpaternity index between grandparents and a grandchild without or with the mother being involved; half sibling index between two children with two mothers being involved; full sibling index among three children; and half sibling index among three children with no, one, or two mothers being involved.@*CONCLUSIONS@#The general formulas given in this study simplify the calculation of KIs and facilitate fast and accurate calculation through programming.

¿Existe una asociación entre polimorfismos de inserción/supresión - 2549 en la región promotora del gen que codifica la vegfa como factor de riesgo y el descargo espontáneo idiopático recurrente en una muestra de mujeres jordanas? / Is there an association between - 2549 Insertion/ Deletion Polymorphisms in the Promotor Region of the Gene Encoding for VEGFA as a Risk Factor and the Idiopathic Recurrent Spontaneous Miscarriage in a sample of Jordanian Women?

Antecedentes: al menos el 50% de los casos de aborto espontáneo recurrente son etiológicamente idiopáticos. Recientemente se han propuesto varios polimorfismos genéticos como factores de riesgo de susceptibilidad a la pérdida del embarazo. Objetivo: El objetivo del presente estudio de casos y controles es establecer la asociación entre los polimorfismos funcionales −2549 I / D en la región promotora del gen del factor de crecimiento endotelial vascular A (VEGFA) y el aborto espontáneo recurrente idiopático (IRSM) en una muestra de las mujeres jordanas. Sujetos y métodos: Se reclutaron 328 sujetos, 103 y 98 mujeres con IRSM primario y secundario, respectivamente, se seleccionaron 127 mujeres normales como grupo de control. Se aisló ADN genómico de una muestra de sangre extraída de cada participante, luego, se genotipificaron los polimorfismos I / D -2549 del gen VEGFA mediante la reacción en cadena de la polimerasa (PCR). Resultados: Los resultados obtenidos revelaron que el polimorfismo ID y el alelo D de VEGFA -2549 polimorfismos I / D tienen las frecuencias más altas en pacientes IRSM tanto primario como secundario, sin diferencia significativa entre los tres grupos en cuanto a polimorfismos y frecuencias alélicas, pacientes con DD + ID Los modelos genéticos tienen una asociación positiva con un alto riesgo de IRSM versus el modelo II, y los pacientes con alelo D son más propensos a tener IRSM que los que tienen el alelo I, no hay diferencia significativa en la asociación de polimorfismos VEGFA -2549 I / D con IRSM en los tres modelos genéticos de los pacientes con IRSM primario y secundario. Conclusión: los pacientes con modelo genético ID de polimorfismos I / D -2549 en la región promotora del gen VEGFA y el alelo D tienen mayor riesgo de IRSM

Background: At least 50% of the cases of recurrent spontaneous miscarriage are aetiologically idiopathic. Recently various genetic polymorphisms have been proposed as susceptibility risk factors for pregnancy loss. Objective: The aim of the present case control study is to establish the association between the functional −2549 I/D polymorphisms in the promoter region of the vascular endothelial growth factor A (VEGFA) gene and idiopathic recurrent spontaneous miscarriage (IRSM) in a sample of Jordanian women. Subjects and methods: 328 subjects were recruited, 103 and 98 women with primary and secondary IRSM, respectively, 127 normal women were selected as a control group. Genomic DNA was isolated from a blood sample withdrawn from each participant, then, -2549 I/D polymorphisms of VEGFA gene were genotyped by Polymerase Chain Reaction (PCR). Results: The obtained results revealed that ID polymorphism and D allele of VEGFA -2549 I/D polymorphisms have the highest frequencies in both primary and secondary IRSM patients, no significant difference between the three groups regarding polymorphisms and allele frequencies, patients with DD+ID genetic models have positive association with high risk of IRSM versus II model, and patients with D allele are more liable to have IRSM than those having I allele, no significant difference in the association of VEGFA -2549 I/D polymorphisms with IRSM in the three genetic models of the primary and secondary IRSM patients. Conclusion: patients with ID genetic model of -2549 I/D polymorphisms in the VEGFA gene's promotor region and D allele have higher risk for IRSM.

Estudios genéticos y neurodesarrollo: De la utilidad al modelo genético / Genetic studies and neurodevelopment. From effectiveness to genetic models]

Los avances en la genética han podido apoyar la sospecha que aportaba la experiencia clínica sobre el gran componente hereditario de la mayor parte de estos trastornos del neurodesarrollo (TND). Los estudios iniciales de heredabilidad, ligamiento o asociación evidenciaron desde los inicios la gran contribución de la variación genotípica a la clínica en general, y a los TND en particular. No debe obviarse la utilidad de los estudios genéticos en el ejercicio clínico, encaminados al diagnóstico etiológico. La mayor parte de los mismos están protocolizados en el estudio de trastornos como la discapacidad intelectual y el autismo; dentro de éstos, la hibridación por arrays cromosómicos ha aportado una mayor rentabilidad diagnóstica respecto a técnicas citogenéticas históricas (3 vs. 10% respectivamente). Sin embargo, la irrupción y rentabilidad de técnicas de genética molecular por secuenciación, particularmente la exómica y genómica en trío, analizando a padres, (tasas diagnósticas del 30-50%), están condicionando la modificación de los algoritmos genéticos en el diagnóstico de trastornos graves del neurodesarrollo. El mayor conocimiento de variantes causales de discapacidad intelectual y autismo está igualmente modificando los modelos teóricos poligénicos establecidos hasta la fecha.

Advances in genetics have been able to support the clinical suspicion on the large hereditary component of most of these neurodevelopmental disorders (NDD). Initial studies on heritability, linkage or association showed from the beginning the great contribution of genotypic variation to the clinic in general, and to NDD in particular. The effectiveness of genetic studies in clinical practice, targeted to aetiological diagnosis, should not be ignored. Most of these are protocolized in the study of disorders such as intellectual disability and autism; within these, the array comparative genomic hybridization have supported a greater diagnostic effectiveness with respect to historical cytogenetic techniques (3 vs. 10% respectively). However, the irruption and success of molecular genetic sequencing techniques, particularly the exome and genome in trio, analyzing the parents (diagnostic rates of 30-50%), are conditioning the modification of the genetic algorithms in the diagnosis of different NDD. The greater knowledge of causal variants in intellectual disability and autism is also modifying the polygenic theoretical models established to date.

Evaluation of genome similarities using a wavelet-domain approach

Abstract INTRODUCTION: Tuberculosis is listed among the top 10 causes of deaths worldwide. The resistant strains causing this disease have been considered to be responsible for public health emergencies and health security threats. As stated by the World Health Organization (WHO), around 558,000 different cases coupled with resistance to rifampicin (the most operative first-line drug) have been estimated to date. Therefore, in order to detect the resistant strains using the genomes of Mycobacterium tuberculosis (MTB), we propose a new methodology for the analysis of genomic similarities that associate the different levels of decomposition of the genome (discrete non-decimated wavelet transform) and the Hurst exponent. METHODS: The signals corresponding to the ten analyzed sequences were obtained by assessing GC content, and then these signals were decomposed using the discrete non-decimated wavelet transform along with the Daubechies wavelet with four null moments at five levels of decomposition. The Hurst exponent was calculated at each decomposition level using five different methods. The cluster analysis was performed using the results obtained for the Hurst exponent. RESULTS: The aggregated variance, differenced aggregated variance, and aggregated absolute value methods presented the formation of three groups, whereas the Peng and R/S methods presented the formation of two groups. The aggregated variance method exhibited the best results with respect to the group formation between similar strains. CONCLUSION: The evaluation of Hurst exponent associated with discrete non-decimated wavelet transform can be used as a measure of similarity between genome sequences, thus leading to a refinement in the analysis.

HDAC Inhibition by Valproic Acid Induces Neuroprotection and Improvement of PD-like Behaviors in LRRK2 R1441G Transgenic Mice

Parkinson’s disease (PD) is one of the late-onset neurodegenerative movement disorder. Major pathological markers of PD include progressive loss of dopaminergic neurons, Lewy body formation, genetic mutations, and environmental factors. Epigenetic regulation of specific gene expression via impaired histone acetylation is associated with neuronal dysfunction in various neurodegenerative diseases. In this study, we hypothesized that histone deacetylase (HDAC) inhibitor, valproic acid (VPA), can improve motor function by enhancing cell survival in PD genetic model mice with LRRK2 R1441G mutation. To address this question, we administered VPA in LRRK2 R1441G transgenic mice to determine whether VPA affects 1) histone acetylation and HDAC expression, 2) dopaminergic neuron survival, 3) inflammatory responses, 4) motor or non-motor symptoms. As results, VPA administration increased histone acetylation level and the number of tyrosine hydroxylase (TH) positive neurons in substantia nigra of LRRK2 R1441G mice. VPA reduced iba-1 positive activated microglia and the mRNA levels of pro-inflammatory marker genes in LRRK2 R1441G mice. In addition, VPA induced the improvement of PD-like motor and non-motor behavior in LRRK2 R1441G mice. These data suggest that the inhibition of HDAC can be further studied as potential future therapeutics for PD.

Calculation of Likelihood Ratio for Identifying Half Sibling Relationship When Both Biological Mothers Participate / 法医学杂志

Objective To derive the formulae for likelihood ratio （LR） calculation of half sibling relationships when both mothers participate. Methods Based on the fact that both biological mothers participate in the identification of half sibling relationship between the two individuals, test hypothesis for the identification of half sibling relationship was established. Conditional probability ratios of genetic evidence under null hypothesis and alternative hypothesis conditions were simplified, and then applied to a real case of half sibling relationship identification. At the same time, the LR of half sibling relationships under the assumption that only a single biological mother or none of the biological mothers participate were respectively calculated. Results In the cases of identification of half sibling relationship from same fathers, with no biological father involved, after the same genetic indicator test analysis, when both biological mothers participate in the identification, the accumulated LR value was higher than that of accumulated LR with only a single biological mother or no parents participating. Conclusion When the autosome STR test is used for the identification and analysis of half sibling relationship between two individuals, the calculation of LR is more simple, intuitive and operable with both mothers participating. The biological mothers should participate in the test as much as possible, otherwise the number of STR loci would need to be increased for a more specific conclusion.

Development of a Post-vitrectomy Injection of N-methyl-N-nitrosourea as a Localized Retinal Degeneration Rabbit Model

Since genetic models for retinal degeneration (RD) in animals larger than rodents have not been firmly established to date, we sought in the present study to develop a new rabbit model of drug-induced RD. First, intravitreal injection of N-methyl-N-nitrosourea (MNU) without vitrectomy in rabbits was performed with different doses. One month after injection, morphological changes in the retinas were identified with ultra-wide-field color fundus photography (FP) and fundus autofluorescence (AF) imaging as well as spectral-domain optical coherence tomography (OCT). Notably, the degree of RD was not consistently correlated with MNU dose. Then, to check the effects of vitrectomy on MNU-induced RD, the intravitreal injection of MNU after vitrectomy in rabbits was also performed with different doses. In OCT, while there were no significant changes in the retinas for injections up to 0.1 mg (i.e., sham, 0.05 mg, and 0.1 mg), outer retinal atrophy and retinal atrophy of the whole layer were observed with MNU injections of 0.3 mg and 0.5 mg, respectively. With this outcome, 0.2 mg MNU was chosen to be injected into rabbit eyes (n=10) at two weeks after vitrectomy for further study. Six weeks after injection, morphological identification with FP, AF, OCT, and histology clearly showed localized outer RD - clearly bordered non-degenerated and degenerated outer retinal area - in all rabbits. We suggest our post-vitrectomy MNU-induced RD rabbit model could be used as an interim animal model for visual prosthetics before the transition to larger animal models.

Investigation of the association of idiopathic male infertility with polymorphisms in the methionine synthase (MTR) gene / 대한생식의학회지

OBJECTIVE: Spermatogenesis is a complex process that is regulated by a number of genes, some of which are involved in folate-dependent 1-carbon metabolism. Methionine synthase (encoded by MTR) is a key enzyme participating in this pathway. This study aimed to investigate the relationship of the MTR 2756A > G polymorphism with idiopathic male fertility in the Iranian population. METHODS: The participants of this study included 100 men with idiopathic infertility and 100 healthy men as the control group. Genotyping of MTR 2756A > G was performed using the polymerase chain reaction and restriction fragment length polymorphism technique. The obtained data were analyzed using SPSS ver. 20.0 with a level of confidence of p G single-nucleotide polymorphism is not a predisposing factor for idiopathic infertility in men.

Global Quantitative Mapping of Enhancers in Rice by STARR-seq / 基因组蛋白质组与生物信息学报·英文版

Enhancers activate transcription in a distance-, orientation-, and position-independent manner, which makes them difficult to be identified. Self-transcribing active regulatory region sequencing (STARR-seq) measures the enhancer activity of millions of DNA fragments in parallel. Here we used STARR-seq to generate a quantitative global map of rice enhancers. Most enhancers were mapped within genes, especially at the 5' untranslated regions (5'UTR) and in coding sequences. Enhancers were also frequently mapped proximal to silent and lowly-expressed genes in transposable element (TE)-rich regions. Analysis of the epigenetic features of enhancers at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and lack the enhancer mark of histone modification H3K4me1. Clustering analysis of enhancers according to their epigenetic marks revealed that about 40% of identified enhancers carried one or more epigenetic marks. Repressive H3K27me3 was frequently enriched with positive marks, H3K4me3 and/or H3K27ac, which together label enhancers. Intergenic enhancers were also predicted based on the location of DHS regions relative to genes, which overlap poorly with STARR-seq enhancers. In summary, we quantitatively identified enhancers by functional analysis in the genome of rice, an important model plant. This work provides a valuable resource for further mechanistic studies in different biological contexts.

How Microbes Shape Their Communities? A Microbial Community Model Based on Functional Genes / 基因组蛋白质组与生物信息学报·英文版

Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction (FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage (AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping (CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.

Evolutionary Genetic Models of Mental Disorders

Psychiatric disorder as dysfunctional behavioural syndrome is a paradoxical phenomenon that is difficult to explain evolutionarily because moderate prevalence rate, high heritability and relatively low fitness are shown. Several evolutionary genetic models have been proposed to address this paradox. In this paper, I explain each model by dividing it into selective neutrality, mutation-selection balance, and balancing selection hypothesis, and discuss the advantages and disadvantages of them. In addition, the feasibility of niche specialization and frequency dependent selection as the plausible explanation about the central paradox is briefly discussed.

Polimorfismos de un solo nucleótido representativos para los alelos clásicos del antígeno leucocitario humano en familias antioqueñas con diabetes mellitus tipo 1 / Classical HLA alleles tag SNP in families from Antioquia with type 1 diabetes mellitus

Resumen Introducción. La región del antígeno leucocitario humano (Human Leukocyte Antigen, HLA) se ha asociado claramente con enfermedades autoinmunitarias, como la diabetes mellitus de tipo 1. Los polimorfismos representativos de un solo nucleótido (tag Single Nucleotide Polymorphism, tag SNP) constituyen una forma alternativa de evaluar los alelos clásicos del HLA. En la población europea se ha reportado un grupo de tag SNP para múltiples alelos clásicos relacionados con la predisposición o la resistencia frente a dicha enfermedad. Objetivo. Validar la metodología basada en los tag SNP enfocada en la inferencia de alelos HLA clásicos, y evaluar su asociación con la diabetes mellitus de tipo 1 en una muestra de familias antioqueñas. Materiales y métodos. Se estudió una muestra de 200 familias antioqueñas con uno a dos hijos afectados por diabetes mellitus de tipo 1. Se genotipificaron 13 SNP mediante el ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction) con cuatro iniciadores, o mediante la PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). Además, se evaluó la validez de los tag SNP de 1.000 genomas reportados en europeos en una muestra de 60 individuos de la población colombiana de Medellín. Se hicieron las pruebas de desequilibrio de la transmisión, de desequilibrio de ligamiento y de equilibrio de Hardy-Weinberg. Resultados. En la población de estudio no se encontró suficiente desequilibrio de ligamiento entre los SNP y los alelos clásicos evaluados, por lo cual no fue posible inferir los alelos clásicos del HLA para el conjunto de familias con diabetes mellitus de tipo 1. El estudio de asociación evidenció que esta región aporta factores tanto de riesgo como de protección para el desarrollo de la enfermedad. Los tag SNP apropiados para la muestra de estudio se determinaron usando los SNP ubicados en la región HLA en la base de datos del 1000 Genomes Project en la mencionada población. Conclusiones. Los patrones de desequilibrio de ligamiento en la población estudiada fueron diferentes a los reportados para la población europea. A pesar de esto, se encontró evidencia clara sobre el papel de la región HLA en el riesgo de padecer diabetes mellitus de tipo 1 en la población de estudio.

abstract Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.

Síndrome de Lynch: aspectos genéticos, clínicos y diagnósticos / Lynch syndrome: genetic, clinical and diagnostic aspects

Esta revisión tiene como objetivo dar a conocer los aspectos genéticos, clínicos y diagnósticos del síndrome de Lynch, además de brindar la información más relevante acerca de la asesoría genética en estos pacientes y las recomendaciones actuales para su seguimiento.

This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.

An ensemble-based likelihood ratio approach for family-based genomic risk prediction / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#As one of the most popular designs used in genetic research, family-based design has been well recognized for its advantages, such as robustness against population stratification and admixture. With vast amounts of genetic data collected from family-based studies, there is a great interest in studying the role of genetic markers from the aspect of risk prediction. This study aims to develop a new statistical approach for family-based risk prediction analysis with an improved prediction accuracy compared with existing methods based on family history.@*METHODS@#In this study, we propose an ensemble-based likelihood ratio (ELR) approach, Fam-ELR, for family-based genomic risk prediction. Fam-ELR incorporates a clustered receiver operating characteristic (ROC) curve method to consider correlations among family samples, and uses a computationally efficient tree-assembling procedure for variable selection and model building.@*RESULTS@#Through simulations, Fam-ELR shows its robustness in various underlying disease models and pedigree structures, and attains better performance than two existing family-based risk prediction methods. In a real-data application to a family-based genome-wide dataset of conduct disorder, Fam-ELR demonstrates its ability to integrate potential risk predictors and interactions into the model for improved accuracy, especially on a genome-wide level.@*CONCLUSIONS@#By comparing existing approaches, such as genetic risk-score approach, Fam-ELR has the capacity of incorporating genetic variants with small or moderate marginal effects and their interactions into an improved risk prediction model. Therefore, it is a robust and useful approach for high-dimensional family-based risk prediction, especially on complex disease with unknown or less known disease etiology.

Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries / 대한정신분열병학회지

OBJECTIVES: Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. METHODS: A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. RESULTS: rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. CONCLUSION: We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Effect of SLCO1B1 T521C on Statin-induced Myotoxicity: A Systematic Review and Meta-analysis

BACKGROUND: This study was performed to clarify the effect of SLCO1B1 T521C on statin-induced myotoxicity. METHODS: The PubMed, Embase, Ovid, and Cochrane Library databases were searched for all published studies between database inception and April 2018. Using Review Manager 5, the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were determined to assess the effect of SLCO1B1 T521C on statin-induced myotoxicity by using different genetic models. RESULTS: Eleven observational studies and one randomized controlled trial were included in the meta-analysis. The pooled analysis showed that the incidence of statin-induced myotoxicity was significantly associated with the SLCO1B1 521C variant allele. Among patients using statins, the incidence of myotoxicity was higher in those carrying the 521TC or 521CC variant than in those carrying the 521TT variant in the dominant model (TC + CC vs TT, OR: 1.57; 95% CI: 1.20, 2.05; p = 0.001). The 521TC genotype was associated with a higher risk of myotoxicity than the 521TT genotype (OR: 1.42; 95% CI: 1.09, 1.86; p = 0.009). Furthermore, the incidence of myotoxicity was higher in 521CC carriers than in 521TC carriers (OR: 1.40; 95% CI: 1.06, 1.83; p = 0.02) and noticeably higher in 521CC carriers than in 521TT carriers (OR: 2.26; 95% CI: 1.23, 4.17; p = 0.009). CONCLUSION: The identification of individuals with the SLCO1B1 521C variant allele prior to the initiation of statin therapy might be useful to predict the risk of toxicity development, determine the individual dose, and prevent myotoxicity.

A Functional Polymorphism in the DRD1 Gene, That Modulates Its Regulation by miR-504, Is Associated with Depressive Symptoms

OBJECTIVE: The aim of this study was to examine a possible association between depressive symptoms and a functional polymorphism (rs686) that modulates the regulation of DRD1 gene by miR-504. METHODS: A total of 239 young Colombian subjects were evaluated with the Patient Health Questionnaire-9 (PHQ-9) scale and genotyped for the rs686 polymorphism. A linear regression model, corrected by age and gender, was used. RESULTS: A significant association between the rs686 polymorphism and PHQ-9 scores was found, under a dominant genetic model (p=0.0094). CONCLUSION: These results provide novel evidence about the growing role of inherited variants in binding sites for brain-expressed miRNAs on depressive symptomatology.

Polymorphism Located in the Upstream Region of the RPS19 Gene (rs2305809) Is Associated With Cervical Cancer: A Case-control Study

Cervical cancer (CC) is caused by persistent human papillomavirus (HPV) infection and affects women worldwide. The progression of an HPV persistent infection to CC is influenced by genetic factors. Three single nucleotide polymorphisms (SNPs) in TP53, NQO1 and RPS19 genes (rs1042522, rs1800566, rs2305809, respectively) were previously associated with CC in European and North American populations. The present case-control study aimed to investigate the association of the SNPs rs1042522, rs1800566, and rs2305809 with CC in an admixed population in southern Brazil. A total of 435 women (106 CC patients and 329 controls) were recruited for this study. All women were interviewed and underwent clinical sampling. SNPs rs1042522 and rs1800566 were evaluated by PCR-RFLP. SNP rs2305809 was determined by real-time PCR. The crude and adjusted ORs with 95% CI were estimated. The recessive genetic model (C/C + C/T) for rs2305809 was more frequent in the control group (79.9%) compared to the cases (69.8%), being associated with CC protection ((adjusted)OR = 0.49; 95% CI: 0.27–0.90). However, the other polymorphisms evaluated did not present significant differences between cases and controls. This study detected a protective association for the recessive genetic model in rs2305809. These results suggest a potential role of the RPS19 gene in CC.

Modelos para avaliação genética da produção de leite no dia do controle nas três primeiras lactações / Models for genetic evaluation of milk yield on the day of control in the three first lactations

Objetivou-se verificar se a utilização do modelo autorregressivo (MAR) é adequada para obtenção de parâmetros genéticos para produção de leite no dia do controle (PLDC) de bovinos leiteiros da raça Gir. Foram analisados 125.191 registros de produções diárias, nas três primeiras lactações, por meio dos modelos de repetibilidade (MREP) e MAR. No MREP, foi considerado o efeito de ambiente de curto prazo; no MAR, foi considerado, também, o efeito de ambiente de longo prazo. Os modelos foram comparados por meio do logaritmo da função de máxima verossimilhança (−2logL) . A herdabilidade estimada pelo MREP foi 0,18; no caso do MAR, as estimativas para primeira, segunda e terceira lactações foram 0,32, 0,28 e 0,26, respectivamente. A estimativa de autocorrelação dos componentes de variância de longo prazo foi próxima de zero, e as de curto prazo foram de alta magnitude para primeira (0,79), segunda (0,79) e terceira (0,81) lactações. Logo, a influência do ambiente de curto prazo dentro de cada lactação não é a mesma. O valor de −2logL mais próximo de zero foi obtido para o MAR (-294.884,7778) em relação ao MREP (-329.266,4810). Assim, o MAR é adequado para obtenção de estimativas de parâmetros genéticos para PLDC nas três primeiras lactações de bovinos leiteiros.(AU)

Aimed to verify if the autoregressive model (MAR) is adequate to obtain genetic parameters for Gyr dairy cattle milk yield on the test day in the three first lactations. Analysis was performed on 125,191 records of daily production of 9,242 cows using repeatability model (MREP) and MAR. On MREP, a long-term environment was considered, on MAR, the short-term environment was also taken into consideration. The models were compared by logarithm of the maximum likelihood function (−2logL) . The heritability estimated using the MREP model was 0.18, while the heritability estimated by MAR for first, second, and third lactations were 0.32, 0.28 and 0.26, respectively. The autocorrelation estimates of the components of long-term variance were close to zero, and those of the short-term were of high magnitude for first (0.79), second (0.79) and third (0.81) lactations. Therefore, the influence of the short-term environment within each lactation is not the same. The value of −2logL closer to zero was obtained for MAR (-294,884.7778) in relation to MREP (-329,266.4810). Thus, MAR is suitable for obtaining genetic parameters estimates for PLDC in the first three lactations of dairy cattle.(AU)

Genetic Polymorphism in MMP9 May Be Associated With Anterior Open Bite in Children

Abstract Anterior open bite (AOB) has a multifactorial etiology caused by the interaction of sucking habits and genetic factors. The aim of this study was to evaluate the association between AOB and polymorphisms in genes that encode Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Four hundred and seventy-two children that presented at least one sucking habit were evaluated. Children were examined clinically for the presence of AOB. Genomic DNA was extracted from saliva. Genotyping of the selected polymorphisms in MMP2, MMP3, MMP9, TIMP1 and TIMP2 was carried out by real-time PCR using the TaqMan method. Allele and genotype frequencies were compared between the groups with and without AOB using the PLINK® software in a free and in a recessive model using a chi-square test. Logistic regression analysis was implemented (p≤0.05). Two hundred nineteen children had AOB while 253 did not. The polymorphism rs17576 in MMP9 was significantly associated with AOB (p=0.009). In a recessive model GG genotype was a protective factor for AOB (p=0.014; OR 4.6, 95%CI 1.3-16.2). In the logistic regression analysis, none of the genes was associated with AOB. In conclusion, the polymorphism rs17576 (glutamine for arginine substitution) in MMP9 was a protective factor for AOB.

Resumo A mordida aberta anterior apresenta uma etiologia multifatorial causada pela interação entre hábitos de sucção e fatores genéticos. O objetivo deste estudo foi avaliar a associação entre mordida aberta anterior e polimorfismo nos genes que codificam as metaloproteinases da matriz (MMPs) e seus inibidores teciduais (TIMPs). Foram avaliadas 472 crianças que apresentvam pelo menos um hábito de sucção. As crianças foram clinicamente examinadas para avaliar a presença de mordida aberta anterior. DNA genômico foi extraído da saliva. A genotipagem dos polimorfismos selecionados em MMP2, MMP3, MMP9, TIMP1 e TIMP2 foi realizada por PCR em tempo real, usando o método de TaqMan. As frequências alélicas e genotípicas foram comparadas entre os grupos com e sem mordida aberta anterior usando o software PLINK®. Duzentas e dezenove crianças apresentavam mordida aberta anterior enquanto 253 não a apresentavam. O polimorfismo rs17576 em MMP9 estava significativamente associado com mordida aberta anterior (p=0,009). No modelo recessivo (GG versus AG+AA) o genótipo GG foi um fator protetor para mordida aberta anterior (p=0,014; OR 4,6; 95%CI 1,3- 16,2). Concluindo, o polimorfismo rs17576 (substituição de glutamina por arginina) em MMP9 está associado com mordida aberta anterior. Os resultados obtidos suportam a hipótese de que fatores genéticos estão envolvidos com a etiologia da mordida aberta anterior.