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Objective: To analyze the association that PTPN1 gene single nucleotide polymorphisms (SNPs) rs941798 and rs914458 have with type 2 diabetes in Peruvian families from Lima. Materials and methods: Twenty-three (23) families consisting of three members each were recruited at the Hospital Nacional Arzobispo Loayza. Peripheral blood samples were collected to obtain the DNA, and then the allele and genotype frequencies of the SNPs. SNP genotyping was performed using the sequencing method. The family-based analysis of the association between SNPs and type 2 diabetes was conducted using the family-based association test (FBAT) program. Results: Three (3) possible genotypes were observed for each SNP, i.e. rs941798 (A>G) and rs914458 (G>C). In one of the assessed models, the family-based association tests showed at the allele level that allele A of SNP rs941798 is associated with type 2 diabetes (p = 0.023). However, after using the Bonferroni correction for multiple comparisons, this association was lost. No association was demonstrated between the SNPs and the disease at any level (allele, genotype or haplotype). Conclusions: No evidence of significant association was found between PTPN1 gene SNPs rs941798 and rs914458 and type 2 diabetes at the studied levels (allele, genotype or haplotype) in Peruvian families from Lima.

The objective was to evaluate the possible morphofunctional and protein stability alterations resulting from Tyrosine amino acid changes by a Histidine at position 269, as well as to correlate with the physiological function of the protein and its probable association with human osteoporosis. Through an in silico analysis based on the information available in the NCBI dbSNP (amino acid change and position) and UNIPROT (sequence in the protein) databases. The impacts of the Y269H modification were analyzed from the tools SIFT, Align-GVGD, SNAP and PROVEAN (function and structure), and PolyPhen-2 (nature of the change). In addition, MuPRO tool (stability changes in the protein) were also used. In silico analysis of the rs1803909 polymorphism demonstrated functional alteration (SIFT tool, Score= 0). As well as, it is estimated that amino acid exchange may be related to damaging alterations (PolyPhen-2, Score= 0.993) and associated with modifications in protein function (PROVEAN, Score= -4.015). In addition, structural (Align-GVGD, Score= 83.33, Class C65) and functional (SNAP, Score= 57) impacts were observed. Complementarily, decreased protein stability arising from Y269H alteration was observed by MuPRO tool, ∆∆G= -1.6731749. However, morphofunctional alterations may be connected to damaging processes and the decreased stability of the protein, thus hindering its action. Furthermore, understanding the morphofunctional and stability changes of rs1803909 may aid in the search for early diagnostic genetic and molecular markers for osteoporosis in humans. El objetivo es evaluar las posibles alteraciones morfofuncionales y de estabilidad proteica que conllevan las modificaciones de los aminoácidos de la Tirosina por una Histidina en la posición 269, así como correlacionarlas con la función fisiológica de la proteína y su probable relación con la osteoporosis humana. Mediante un análisis in silico basado en la información disponible en las bases de datos NCBI dbSNP (cambio y posición de aminoácidos) y UNIPROT (secuencia en la proteína). Los impactos de la modificación Y269H se analizaron a partir de las herramientas SIFT, Align-GVGD, SNAP y PROVEAN (función y estructura), y PolyPhen-2 (naturaleza del cambio). Además, se utilizaron la herramienta MuPRO (cambios de estabilidad en la proteína). El análisis in silico del polimorfismo rs1803909 demostró una alteración funcional (herramienta SIFT, Puntuación= 0). Además, se estima que el intercambio de aminoácidos puede estar relacionado con cambios perjudiciales (PolyPhen-2, Puntuación= 0,993) y asociado a modificaciones en la función de las proteínas (PROVEAN, Puntuación= -4,015). Además, se observaron impactos estructurales (Align-GVGD, Puntuación= 83,33, Clase C65) y funcionales (SNAP, Puntuación= 57). Complementariamente, se observó una disminución de la estabilidad de la proteína derivada de la alteración Y269H mediante la herramienta MuPRO, ∆∆G= -1,6731749. Sin embargo, las alteraciones morfofuncionales pueden estar vinculadas a procesos perjudiciales y a la disminución de la estabilidad de la proteína, dificultando así su acción. Además, la comprensión de las alteraciones morfofuncionales y de estabilidad del rs1803909 puede ayudar en la búsqueda de marcadores genéticos y moleculares de diagnóstico precoz de la osteoporosis en humanos. Objetivou-se avaliar as possíveis alterações morfofuncionais e de estabilidade proteica decorrentes das alterações dos aminoácidos Tirosina por uma Histidina na posição 269, bem como, correlacionar com a função fisiológica da proteína e sua provável ligação com a osteoporose humana. Por meio de uma análise in silico com base nas informações disponíveis nos bancos de dados NCBI dbSNP (mudança de aminoácidos e posição) e UNIPROT (sequência na proteína). Os impactos da modificação Y269H foram analisados a partir das ferramentas SIFT, Align-GVGD, SNAP e PROVEAN (função e estrutura), e PolyPhen-2 (natureza da alteração). Além disso, utilizou-se também a ferramenta MuPRO (alterações de estabilidade na proteína). A análise in silico do polimorfismo rs1803909 demonstrou alteração funcional (ferramenta SIFT, Score= 0). Bem como, estima-se que a troca de aminoácidos pode estar relacionada a alterações danosas (PolyPhen-2, Score= 0,993) e associada a modificações na função da proteína (PROVEAN, Score= -4.015). Além disso, foram observados impactos estruturais (Align-GVGD, Score= 83,33, Classe C65) e funcionais (SNAP, Score= 57). De forma complementar, observou-se diminuição da estabilidade proteica decorrente da alteração Y269H pela ferramenta MuPRO, ∆∆G= -1.6731749. Contudo, as alterações morfofuncionais podem estar ligadas a processos danosos e a diminuição de estabilidade da proteína, dificultando assim a sua ação. Além disso, a compreensão das alterações morfofuncionais e de estabilidade do rs1803909 podem auxiliar na busca por marcadores genéticos e moleculares de diagnóstico precoce para a osteoporose em humanos.

This study aims to investigate factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentration in Brazilian adults considering sociodemographic and lifestyle factors, as well as vitamin D-related single nucleotide polymorphisms (SNPs). This is a cross-sectional study (n = 491; 34-79y; 251 women), nested within a prospective cohort (Pró-Saúde Study). Associations between serum 25(OH)D and sociodemographic characteristics, diet, use of supplement, physical activity, season of blood collection, body fat, skin type, sun exposure index, and SNPs CYP2R1-rs10741657 and GC-rs2282679 were explored by multiple linear regression. The prevalence of serum 25(OH)D < 50nmol/L was 55%. Serum 25(OH)D was lower among women (β = -4.38; 95%CI: -8.02; -0.74), those with higher visceral fat (β = -4.02; 95%CI: -5.92; -2.12), and those with AC and CC genotypes for GC-rs2282679 (β = -6.84; 95%CI: -10.09; -3.59; β = -10.63; 95%CI: -17.52; -3.74, respectively). Factors directly associated with serum 25(OH)D included summer (β = 20.14; 95%CI: 14.38; 25.90), intermediate skin type (β = 6.16; 95%CI: 2.52; 9.80), higher sun exposure (β = 0.49; 95%CI: 0.22; 0.75), vitamin D intake (β = 0.48; 95%CI: 0.03; 0.93), and physical activity (β = 4.65; 95%CI: 1.54; 7.76). Besides physical activity, diet, and sun exposure, non-modifiable factors, such as GC genotypes must be considered when evaluating vitamin D insufficiency in mixed-race populations. Moreover, high visceral fat in association with poorer vitamin D status deserve attention given that both conditions are unfavorably related with chronic and acute health outcomes. Este estudo teve como objetivo investigar fatores associados com as concentrações séricas de 25-hidroxivitamina [25(OH)D] em adultos brasileiros de acordo com fatores sociodemográficos e de estilo de vida, assim como de polimorfismos de nucleotídeo único (SNPs) relacionados à vitamina D. Este é um estudo transversal (n = 491; 34-79 anos; 251 mulheres) aninhado em uma coorte prospectiva (Estudo Pró-Saúde). Associações entre a 25(OH)D sérica e características sociodemográficas, consumo alimentar, uso de suplementos, atividade física, estação do ano na coleta da amostra de sangue, gordura corporal, fototipo de pele, índice de exposição solar e SNPs CYP2R1-rs10741657 e GC-rs2282679, explorados por regressão multilinear. A prevalência de 25(OH)D sérica < 50nmol/L foi 55%. A concentração sérica de 25(OH)D foi menor entre mulheres (β = -4,38; IC95%: -8,02; -0,74), indivíduos com mais gordura visceral (β = -4,02; IC95%: -5,92; -2,12) e genótipos AC e CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 e β = -10,63; IC95%: -17,52; -3,74, respectivamente). Os fatores associados diretamente à 25(OH)D sérica incluíram os meses de verão (β = 20,14; IC95%: 14,38; 25,90), fototipo intermediário (β = 6,16; IC95%: 2,52; 9,80), maior exposição solar (β = 0,49; IC95%: 0,22; 0,75), ingestão de vitamina D (β = 0,48; IC95%: 0,03; 0,93) e atividade física (β = 4,65; IC95%: 1,54; 7,76). Além de atividade física, dieta e exposição solar, fatores não modificáveis, tais como variantes do gene GC devem ser considerados na avaliação da deficiência de vitamina D em populações miscigenadas. Além disso, merece atenção a associação entre a gordura visceral elevada e o pior estado de vitamina D, uma vez que ambas as condições implicam em desfechos de saúde desfavoráveis, tanto crônicos quanto agudos. Nuestro objetivo fue investigar factores asociados con la concentración sérica 25-hidroxivitamina D [25(OH)D] en adultos brasileños, considerando factores sociodemográficos y de vida, así como también los polimorfismos de nucleótido único relacionados con la vitamina D (SNPs). Se trata de un estudio transversal (n = 491; 34-79 años; 251 mujeres), anidado dentro de una cohorte prospectiva (Estudio Pro-Salud). Se investigaron las asociaciones entre concentración sérica 25(OH)D y características sociodemográficas, ingesta alimentaria, uso de suplementos, actividad física, estación del año de recogida de muestras de sangre, grasa corporal, tipo de piel, índice de exposición al sol, y SNPs CYP2R1-rs10741657 y GC-rs2282679 mediante una regresión múltiple lineal. La prevalencia sérica 25(OH)D < 50nmol/L fue 55%. La 25(OH)D sérica fue menor entre las mujeres (β = -4,38; IC95%: -8,02; -0,74), quienes tenían alta grasa visceral (β = -4,02; IC95%: -5,92; -2,12), genotipos AC y CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 y β = -10,63; IC95%: -17,52; -3,74, respectivamente). Los factores directamente asociados con la concentración sérica 25(OH)D incluyeron verano (β = 20,14; IC95%: 14,38; 25,90), tipo de piel intermedia (β = 6,16; IC95%: 2,52; 9,80), más alta exposición al sol (β = 0,49; IC95%: 0,22; 0,75), toma de vitamina D (β = 0,48; IC95%: 0,03; 0,93) y actividad física (β = 4,65; IC95%: 1,54; 7,76). Además de la actividad física, dieta y exposición al sol, los factores no modificables, tales como genotipos GC, necesitan tenerse en cuenta cuando se está evaluando la insuficiencia de vitamina D en poblaciones mestizas. Asimismo, las implicaciones de la asociación de una alta grasa visceral con un estatus más pobre de vitamina D merece que se le preste atención, puesto que ambas condiciones de salud están relacionadas desfavorablemente con resultados de salud graves y crónicos.

Genetic factors contribute to susceptibility and resistance to fluoride exposure. The aim of this systematic review was to identify alleles/genotypes of single nucleotide polymorphisms (SNPs) associated with dental fluorosis (DF) and to identify them as protective or risk factors. PubMed, ScienceDirect, Cochrane Library, Scopus and Web of Science were searched for articles; the last search was performed in August 2022. Human studies that analyzed the relationship between SNPs and DF published in English were included; systematic reviews and meta-analyses were excluded. Methodological quality was graded using the Joanna Briggs Institute checklist and risk of bias was assessed using the Cochrane Collaboration’s tool. Eighteen articles were included, 44% of which showed high methodological quality and data from 5625 participants aged 6 to 75 years were analyzed. The SNPs COL1A2, ESR2, DLX1, DLX2, AMBN, TUFT1, TFIP11, miRNA17, and SOD2 were considered risk factors, and ESR1, MMP20, and ENAM were considered protective factors. In conclusion, there are alleles and genotypes of different single nucleotide polymorphisms involved in increasing or decreasing the risk of developing dental fluorosis.

Objective: the aim of this work was to explain the implications of the genetic profile (TNF-α polymorphisms in the region-308) in the outcome of different pathologies; and explain how this profile is obtained in the laboratory. Methodology: The salting out technique, according to Miller et al. (1988) was used to explain the reader how the genetic profile of TNF-α is obtained to foresee the outcome of pathologies that are modulated by this cytokine. Results: the product of the amplified digestion of TNF-α genes was obtained, photographed and explained for the reader. Conclusions: the genetic profile may be useful as a predictor for the outcome of different pathologies, so that doctors and dentists may choose the best therapy for each patient. Objetivo: el objetivo de este trabajo fue explicar las implicaciones del perfil genético (polimorfismos en la región-308 del TNF-α) en la evolución de diferentes patologías; y explicar cómo se obtiene este perfil en el laboratorio. Metodología: La técnica de salting out, según Miller et al. (1988) se utilizó para explicar al lector cómo se obtiene el perfil genético de TNF-α para prever el resultado de patologías que son moduladas por esta citoquina. Resultados: Se obtuvo, fotografió y explicó al lector el producto de la digestión amplificada de los genes TNF-α. Conclusiones: el perfil genético puede ser útil como predictor del desenlace de diferentes patologías, de modo que médicos y odontólogos puedan elegir la mejor terapia para cada paciente. Objetivo: o objetivo deste trabalho foi explicar as implicações do perfil genético (polimorfismos do TNF-α na região 308) no desfecho de diferentes patologias; e explicar como esse perfil é obtido em laboratório. Metodologia: A técnica de salting out, segundo Miller et al. (1988) foi utilizado para explicar ao leitor como o perfil genético do TNF-α é obtido para prever o desfecho de patologias que são moduladas por essa citocina. Resultados: o produto da digestão amplificada dos genes do TNF-α foi obtido, fotografado e explicado ao leitor. Conclusões: o perfil genético pode ser útil como preditor de desfecho de diferentes patologias, para que médicos e dentistas possam escolher a melhor terapia para cada paciente.

This research was funded by FEDER and Foundation for Science and Technology (FCT), grant number POCI-01-0145-FEDER-028159 and POCI-01-0145-FEDER-030782); by Fondo de Investigaciones Sanitarias (Madrid, Spain), grant number ISCIII-FEDER PI20/01845, ISCIII-FEDER PI12/02688, and ISCIII-FEDER PI17/02276. B.S.M. was funded by FCT, grant number DL 57/2016. A.C.A. was funded by FCT, grant number POCI-01-0145-FEDER-028159. C.C. was funded by FCT, grant number CEECIND/04058/2018. A.C. was funded by FCT, grant number CEECIND/03628/2017., The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical reasons., Simple Summary Acute myeloid leukemia (AML) is a hematological neoplasm with a very poor survival rate. To date, diagnostic tools to monitor individuals at higher risk of developing AML are scarce. Single nucleotide polymorphisms (SNPs) have emerged as good candidates for disease prevention. AML is characterized by altered autophagy, a vital mechanism to remove and recycle unnecessary or dysfunctional cellular components. ATG10 is one of the autophagy core genes involved in the autophagosome formation. We hypothesize that SNPs located in regulatory regions of the ATG10 gene could predispose individuals to AML development. We therefore genotyped three SNPs within the ATG10 locus. We identified the ATG10(rs3734114) as a potential risk factor for developing AML, whereas the ATG10(rs1864182) was associated with decreased risk. These findings highlight ATG10 as a key regulator of susceptibility to AML. Furthermore, we believe that ATG10 SNPs could be exploited in the clinical setting as an AML prevention strategy. Acute myeloid leukemia (AML) is the most common acute leukemia, characterized by a heterogeneous genetic landscape contributing, among others, to the occurrence of metabolic reprogramming. Autophagy, a key player on metabolism, plays an essential role in AML. Here, we examined the association of three potentially functional genetic polymorphisms in the ATG10 gene, central for the autophagosome formation. We screened a multicenter cohort involving 309 AML patients and 356 healthy subjects for three ATG10 SNPs: rs1864182T>G, rs1864183C>T and rs3734114T>C. The functional consequences of the ATG10 SNPs in its canonical function were investigated in vitro using peripheral blood mononuclear cells from a cohort of 46 healthy individuals. Logistic regression analysis adjusted for age and gender revealed that patients carrying the ATG10(rs1864182G) allele showed a significantly decreased risk of developing AML (OR [odds ratio] = 0.58, p = 0.001), whereas patients carrying the homozygous ATG10(rs3734114C) allele had a significantly increased risk of developing AML (OR = 2.70, p = 0.004). Functional analysis showed that individuals carrying the ATG10(rs1864182G) allele had decreased autophagy when compared to homozygous major allele carriers. Our results uncover the potential of screening for ATG10 genetic variants in AML prevention strategies, in particular for subjects carrying other AML risk factors such as elderly individuals with clonal hematopoiesis of indeterminate potential., European Commission, Portuguese Foundation for Science and Technology European Commission POCI-01-0145-FEDER-028159 POCI-01-0145-FEDER-030782, Instituto de Salud Carlos III ISCIII-FEDER PI20/01845 ISCIII-FEDER PI12/02688 ISCIII-FEDER PI17/02276, Portuguese Foundation for Science and Technology European Commission POCI-01-0145-FEDER-028159 DL 57/2016 CEECIND/04058/2018 CEECIND/03628/2017

This study was supported by grants PI17/02276 and PI20/01845 from Fondo de Investigaciones Sanitarias (Madrid, Spain) and by intramural funds of GENYO and FIBAO foundation (Granada, Spain). This study was also supported by the Novo Nordisk Fonden (NNF15OC0016932, VA) and Knud og Edith Eriksens Mindefond (VA) and Gigtforeningen (A2037, A3570, VA). JS and KB-K were supported by the grant No. 2016/21/B/NZ5/01901 from the National Science Centre (Poland). MGN was supported by a Spinoza grant from the Netherlands Organization for Scientific Research. YL was supported by an ERC Starting Grant (948207) and the Radboud University Medical Centre Hypatia Grant (2018) for Scientific Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (DDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (perallele ORMeta=0.83, PMeta=0.000077; PHet=0.61). In addition, we found that each copy of the LRRC55rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; PHet=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; PHet=0.45; PInteraction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the metaanalysis also showed overall and RF-specific associations for the MAFBrs6071980 and CNTN5rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; PHet=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; PHet=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; PHet=0.12; PInteraction=0.032). Mechanistically, we found that subjects carrying the LINC02549rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated., Instituto de Salud Carlos III PI17/02276 PI20/01845, GENYO foundation (Granada, Spain), FIBAO foundation (Granada, Spain), Novo Nordisk Foundation NNF15OC0016932, Knud og Edith Eriksens Mindefond, Gigtforeningen A2037 A3570, National Science Centre, Poland 2016/21/B/NZ5/01901, Spinoza grant from the Netherlands Organization for Scientific Research, European Research Council (ERC) European Commission 948207, Radboud University Medical Centre Hypatia Grant (2018)

Polypoidal choroidal vasculopathy (PCV) is usually regarded as a subtype of choroidal neovascularization (CNV) that is secondary to age-related macular degeneration (AMD) characterized by choroidal vessel branching, ending in polypoidal lesions. Despite their close association, PCV and neovascular AMD have shown differences, especially regarding patients' treatment response. Currently, antivascular endothelial growth factor (anti-VEGF) drugs, such as ranibizumab, bevacizumab and aflibercept, have demonstrated their efficacy in CNV patients. However, in PCV, anti-VEGF treatments have shown inconclusive results. Many genetic polymorphisms have been associated with a variable response in exudative/wet AMD patients. Thus, the aim of this study is to explore the genetic variants affecting anti-VEGF drug response in PCV patients. In this regard, we performed a systematic review and meta-analysis. We found four variants (CFH I62V, CFH Y402H, ARMS2 A69S, and HTRA1-62A/G) that have been significantly related to response. Among them, the ARMS2 A69S variant is assessed in our meta-analysis. In conclusion, in order to implement anti-VEGF pharmacogenetics in clinical routines, further studies should be performed, distinguishing physio-pathogenic circumstances between PCV and exudative AMD and the combined effect on treatment response of different genetic variants. Yes

Introduction: Studies have suggested that pentraxin 3 (PTX3) and Mannose Binding Lectin (MBL) may interfere with cognitive processes. Objective: Identify data reported in the literature involving cognition, PTX3 and MBL. Materials and Methods: The research was done in five databases and the selection of studies was performed in two stages. The first involved review of titles and abstracts. Then the full articles were read and those that did not meet the eligibility criteria were excluded. Results: A total of 3,097 titles and abstracts were selected, but 3,089 were excluded. Finally, 8 articles were included in the review. The articles pointed out that high levels of PTX-3 could be predictors of cognitive impairment while high levels of MBL could have a protective effect on cognition. Conclusion: The current studies are still contradictory and inconclusive, but they lead us to reflect on possible genetic influences of innate immunity in the Central Nervous System. Further research involving the effects of PTX-3 and MBL and its variants on cognition are necessary. Introducción: Los estudios han sugerido que la pentraxina 3 (PTX3) y la lectina de unión a manosa (MBL) pueden interferir con los procesos cognitivos. Objetivo: Identificar los datos reportados en la literatura relacionados con la cognición, PTX3 y MBL. Materiales y métodos: La investigación se realizó en cinco bases de datos y la selección de estudios se realizó en dos etapas. La primera implicó la revisión de títulos y resúmenes. Luego se leyeron los artículos completos y se excluyeron aquellos que no cumplían con los criterios de elegibilidad. Resultados: Se seleccionaron un total de 3.097 títulos y resúmenes, pero se excluyeron 3.089. Finalmente, se incluyeron 8 artículos en la revisión. Los artículos señalaron que los niveles altos de PTX-3 podrían ser predictores de deterioro cognitivo, mientras que los niveles altos de MBL podrían tener un efecto protector sobre la cognición. Conclusión: Los estudios actuales siguen siendo contradictorios y no concluyentes, pero nos llevan a reflexionar sobre posibles influencias genéticas de la inmunidad innata en el Sistema Nervioso Central. Se necesitan más investigaciones que involucren los efectos de PTX-3 y MBL y sus variantes en la cognición. Introdução: Estudos têm sugerido que a pentraxina 3 (PTX3) e a Lectina de Ligação a Manose (MBL) podem interferir nos processos cognitivos. Objetivo: Identificar dados relatados na literatura envolvendo cognição, PTX3 e MBL. Materiais e Métodos: A pesquisa foi realizada em cinco bases de dados e a seleção dos estudos foi realizada em duas etapas. O primeiro envolveu revisão de títulos e resumos. Em seguida, os artigos completos foram lidos e aqueles que não atenderam aos critérios de elegibilidade foram excluídos. Resultados: Foram selecionados 3.097 títulos e resumos, mas 3.089 foram excluídos. Por fim, 8 artigos foram incluídos na revisão. Os artigos apontaram que altos níveis de PTX-3 podem ser preditores de comprometimento cognitivo, enquanto altos níveis de MBL podem ter um efeito protetor sobre a cognição. Conclusão: Os estudos atuais ainda são contraditórios e inconclusivos, mas nos levam a refletir sobre as possíveis influências genéticas da imunidade inata no Sistema Nervoso Central. Mais pesquisas envolvendo os efeitos da PTX-3 e MBL e suas variantes na cognição são necessárias.

Introduction: Single nucleotide polymorphisms (SNPs) in the BDNF, COMT, CBR1 and CCK genes have been associated with the process of fear extinction in humans. Since fear extinction plays a key role in recovering from psychological trauma, there is a possibility that these genes modulate the risk of developing post-traumatic stress disorder (PTSD). Objective: To assess unilocus and multilocus associations between SNPs in the BDNF, COMT, CBR1 and CCK genes and the risk of developing PTSD. Materials and methods: 129 inhabitants of the municipality of Itagüí, Colombia, who had experienced psychological trauma at least once, were genotyped for these polymorphisms (38 cases of PTSD and 91 controls). Logistic regression was used to perform unilocus and multilocus association tests for single SNPs and existing SNP-SNP genotypic combinations. Results: No unilocus associations were found, but interactions between the BDNF and CBR1 genes and between the COMT and CCK genes were observed. Of these interactions, the genotypic combinations that behaved as risk factors were AG-AA (OR=13.52, p

Background: The interaction between obesity and genetic traits on high density lipoprotein (HDL) levels has been extensively studied. The variance of serum HDL has a strong genetic heritability, although the studied variant only explains a small part of this variation. The goal of this study was to investigate the associations between the apolipoprotein type 2 (APOA2) rs3813627 single nucleotide polymorphism (SNP) and anthropometric and biochemical variables, though body mass index (BMI). Methods: This study included 153 subjects (91 overweight/obese (BMI&sup3, 25 kg/m2) and 62 non-obese individuals (BMI &lt, 25 kg/m2)). The APOA2 rs3813627 SNP was selected and genotyped. Genotype analysis was performed to analyze the associations between APOA2 SNPs and anthropometric and biochemical variables through BMI. Results: The APOA2 rs3813627 TT genotype was associated with low HDL levels in comparison with the APOA2 rs3813627 GG and GT genotype in overweight/obese individuals, but not in the non-obese subjects (p &lt, 0.05). The same trend was observed in the apolipoprotein type 1 (APOA1) protein levels (p &lt, 0.05). Correlation analysis revealed a negative correlation between HDL and APOA1 levels and APOA2 rs3813627 SNP under recessive model (p &lt, 0.05). The odds ratio for low HDL levels was 3.76 and 3.94 for low APOA1 levels. The mediation analysis of APOA2 rs3813627 SNP through BMI showed a full mediation on HDL and partial mediation on APOA1 levels (p &lt, 0.05). Bioinformatic analysis showed that rs3813627 lies in the APOA2 promoter and overlaps motifs for several bound transcription factors. Conclusion: On the basis of these data, the APOA2 rs3813627 SNP is associated with low HDL and APOA1 levels susceptibility, and this effect was mediated by an increased BMI.

Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, different genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men. However, these alterations only explain around 25% of azoospermic cases, with the remaining patients showing an idiopathic origin. Recent studies clearly suggest that the so-called idiopathic NOA has a complex aetiology with a polygenic inheritance, which may alter the spermatogenic process. Although we are far from a complete understanding of the molecular mechanisms underlying NOA, the use of the new technologies for genetic analysis has enabled a considerable increase in knowledge during the last years. In this review, we will provide a comprehensive and updated overview of the genetic basis of NOA, with a special focus on the possible application of the recent insights in clinical practice. Yes

D.C., F.C., and M.G. conceived and designed the study. A.M. and M.G. performed labwork. A.M., F.C., D.C., and M.G. drafted the manuscript. A.M., F.C., D.C., and M.G. performed data quality control and statistical analyses. All other authors provided samples and data. All authors critically read, commented, and approved the manuscript., Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10−3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic= 1.43; 95% CI 1.15–1.77; P = 1.35 × 10−3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development

O amendoim forrageiro (Arachis pintoi Krapov. e W.C. Greg.) tem apresentado resultados importantes na pecuária por seu alto valor nutritivo, o que tem contribuído no aumento da produção de leite, ganho de peso no gado de corte e redução no tempo de abate em até nove meses. Além disso, seu uso como cobertura verde em consórcios com culturas comerciais tem contribuído na redução da erosão, manutenção da umidade do solo, ciclagem de nutrientes, fixação biológica de nitrogênio e baixas emissões de óxido nitroso. O uso de sequenciamento nova geração (NGS) pode auxiliar no conhecimento da biologia da espécie e desenvolvimento de novas cultivares. O objetivo do presente trabalho foi analisar o genoma funcional de Arachis pintoi por meio de dados de RNA-Seq e desenvolver novos marcadores moleculares single nucleotide polymorphisms (SNP) e microssatélites (SSR). Foram realizadas modificações no protocolo de cloreto de lítio para isolamento de RNA total que ajudaram a eliminar problemas associados com a presença de altas concentrações de metabólitos secundários em folhas de amendoim forrageiro e sem sinais de degradação. O RNA de duas cultivares (Belomonte e Amarillo MG-100) foi extraído e utilizado para montagem das bibliotecas, as quais foram sequenciadas e tiveram seu genoma funcional montado com o programa Trinity e metodologia de novo. O sequenciamento gerou aproximadamente 223 milhões de pair-end reads de alta qualidade. Um total de 98.432 transcritos com comprimento médio de 1.102,2 bp foram obtidos. O valor de N50 e a taxa de alinhamento completo foram 1.924 bp e 95%, respectivamente. A função molecular (36,0%) e o processo biológico (35,8%) apresentaram a maioria dos termos da Ontologia Genética atribuídos, enquanto em componente celular (28,2%) foi atribuído o menor número. Uma busca por SNPs funcionais e marcadores SSR identificou 374.385 e 4.461, respectivamente. Cento e oitenta e seis marcadores SSR foram selecionados para validação, dos quais 63 (33,87%) foram polimórficos com média de 7,37 alelos por loco. Os marcadores apresentaram elevados valores médios para conteúdo de informação polimórfica (PIC = 0,70) e poder discriminatório (D = 0,80). O marcador Ap(CT)75 foi capaz de realizar o fingerpriting das cultivares Belomonte, Amarillo MG-100, Alqueire 1, e BRS Mandobi, identificando perfis únicos. Trinta e três SSRs foram avaliados quanto à transferibilidade para amendoim e outras seis espécies silvestres do gênero Arachis, o que resultou em amplificação cruzada variável (63,64 a 100%). O loco Ap(CT)68 permitiu a certificação entre 229 cruzamentos. O polimorfismo dos alelos foi detectado em gel de agarose, permitindo a redução de custos e tempo necessário para o processo de identificação do híbrido. O conjunto dos resultados apresentados neste trabalho permitirão a aplicação de técnicas moleculares modernas como associação genômica, expressão diferencial e seleção genômica, os quais contribuirão significativamente para o conhecimento da biologia de A. pintoi e avanço do programa de melhoramento de Arachis. Forage peanuts (Arachis pintoi Krapov. and W.C. Greg.) has shown important results in livestock due to the high nutritional value, which has contributed to the increase in milk production, weight gain in beef cattle, and reduction in slaughter time by up to nine months. In addition, its use as green cover in associations with commercial crops has contributing to the erosion reduction, maintenance of soil moisture, nutrient cycling, biological nitrogen fixation and low nitrous oxide emissions. The use of next generation sequencing (NGS) can assist in understanding the biology of the species and the development of new cultivars. The objective of the present work was to analyze the functional genome of Arachis pintoi using RNA-Seq data and to develop new single nucleotide polymorphisms (SNP) and microsatellite (SSR) molecular markers. Modifications in lithium chloride protocol were performed for total RNA isolation that helped eliminate the problems associated with the presence of high concentrations of secondary metabolites in forage peanut leaves, and lacked signs of degradation. The RNA of two cultivars (Belomonte and Amarillo MG-100) was extracted and used to assemble the libraries, which were sequenced and had their transcriptome assembled with Trinity program and de novo methodology. The sequencing output generated approximately 223 million high-quality pair-end reads. A total of 98,432 transcripts with an average length of 1,102.2 bp were obtained. The N50 value and complete alignment rate were 1,924 bp and 95 %, respectively. The molecular function (36.0%) and biological process (35.8%) presented the majority of the Gene Ontology terms assigned, whereas in the cellular component (28.2%) were assigned the smaller number. A search for functional SNPs and SSRs markers identified 374,385 and 4,461, respectively. One hundred eighty-six SSR markers were selected for validation, of which 63 (33.87%) were polymorphic with average of 7.37 alleles per locus. The markers presented high average for polymorphic information content (PIC = 0.70) and discriminatory power (D = 0.80). The Ap(CT)75 marker was able to identify unique profiles among Belomonte, Amarillo MG-100, Alqueire 1, and BRS Mandobi. Thirty-three SSRs were evaluated for the transferability to peanut and other six wild species from Arachis genus, which resulted in variable cross-species amplification (63.64 to 100%). The Ap(CT)68 locus allowed the certification among 229 crosses. The allele polymorphism was detected on agarose gel, allowing the reduction of costs and time required for the hybrid identification process. The set of results presented in this work will allow the application of modern molecular techniques such as genomic association, differential expression and genomic selection, which will significantly contribute to the knowledge of the biology of A. pintoi and the advancement of the peanut breeding program. Made available in DSpace on 2020-12-04T09:03:16Z (GMT). No. of bitstreams: 1 27025.pdf: 2285453 bytes, checksum: 96953c58597a7ce5f1be96471afa0e5a (MD5) Previous issue date: 2020 Tese (Doutorado em Biodiversidade e Conservação) - Programa de Pós-graduação em Biodiversidade e Biotecnologia da Rede BIONORTE, Universidade Federal do Acre, Rio Branco. Orientador: Tatiana de Campos. Co-orientadora: Carla Cristina da Silva.

El objetivo del presente trabajo fue caracterizar el polimorfismo de nucleótido simples 316 y 4751 del gen CAPN y 2959 y CAST1 del gen CAST en la raza bovina criolla colombiana Hartón del Valle. Se genotiparon mediante PCR-RFLP 126 individuos para los cuatro loci. Todos los marcadores fueron polimórficos. El genotipo CC del locus CAPN-316 y el heterocigoto en los otros tres loci tuvieron mayor frecuencia. Las frecuencias de los alelos asociados positivamente con calidad de la carne fueron de C= 21.8 ± 17.5% en CAPN-316, C = 48.4 ± 10.1% en CAPN-4751, T = 52.5 ± 11.4% en CAST-1 y A = 65.1 ± 15.5% en CAST-2959. En todo los loci la Ho (0.599 ± 0.248) fue más alta que la He (0.410 ± 0.081) con valores negativos de FIS y FIT y con desviaciones de EHW solo en CAPN-4751. El valor de FST fue de 0.048 (p < 0.05) y el AMOVA mostró que la variación en estos loci se debía en mayor parte a los individuos (97%). Lo anterior puede ser indicativo de que esta raza presenta predisposición genética para la producción de carne con perfiles de calidad., The objective of the present work was to characterize the simple nucleotide polymorphism 316 and 4751 of the CAPN and 2959 gene and CAST1 of the CAST gene in the Colombian creole breed Hartón del Valle. A total of 126 individuals were genotyped by PCR-RFLP for the four loci. All markers were polymorphic. The CC genotype of the CAPN-316 locus and the heterozygote in the other three loci were more frequent. The frequencies of the alleles positively associated with meat quality were C = 21.8 ± 17.5% in CAPN-316, C = 48.4 ± 10.1% in CAPN-4751, T = 52.5 ± 11.4% in CAST-1 and A = 65.1 ± 15.5% in CAST-2959. In all the loci the Ho (0.599 ± 0.248) was higher than the He (0.410 ± 0.081) with negative values of FIS and FIT and with deviations of EHW only in CAPN-4751. The FST value was 0.048 (p

El objetivo de este estudio fue evaluar la presencia de polimorfismos de nucleótido simple (SNP´s) en genes de μ-calpaína (CAPN-1) y calpastatina (CAST) asociados a atributos de terneza en carne bovina y relacionar la presencia de estos genes con las diferencias esperadas de progenie (DEP´s) para características de crecimiento. Se recolectaron muestras de sangre (n = 82) de machos reproductores Brahman de registro, pertenecientes a 7 haciendas, ubicadas en 4 regiones geográficas de Costa Rica. Todos los individuos se encontraban incluidos en el programa de mejoramiento genético de bovinos de carne, dirigido por la Corporación Ganadera (CORFOGA). Las muestras de sangre fueron analizadas en el laboratorio de biotecnología molecular del Instituto Tecnológico de Costa Rica, Sede San Carlos. Se analizó la presencia de los SNP´s CAPN316, CAPN4751 (gen CAPN- 1) y CAST2959 (gen CAST). Se estimaron las frecuencias alélicas en CAPN316 para C (0,006), G (0,994) y genotipos CC (0,000), CG (0,013) y GG (0,987). El marcador CAPN4751 presentó frecuencias alélicas para C (0,165), T (0,835), así como frecuencias genotípicas de CC (0,025), CT (0,279) y TT (0,696). El polimorfismo de nucleótido simple CAST2959 presentó frecuencias alélicas para A (0,667), G (0,333), y genotípicas para AA (0,432), AG (0,469) y GG (0,099). Se observó una baja frecuencia del alelo favorable C del gen CAPN316, sin embargo, se observó una distribución de frecuencias alélicas más equilibrada en CAPN4751 y CAST2959. En el análisis de asociación entre SNP´s favorables y DEP´s, se encontraron asociaciones muy débiles o incluso ausencia de correlación.

Introducción. La anemia perioperatoria es una complicación común de la cirugía cardiovascular. Pacientes con el alelo T del polimorfismo rs11549465 de HIF-1α podrían tener niveles alterados de hemoglobina y lactato antes, durante y después de la cirugía, en comparación con los del ancestral. Esto, por un aumento en la estabilidad de HIF-1α causado por este.Objetivo. Describir la frecuencia del alelo T en pacientes de cirugía cardiovascular programada y su relación con los niveles de hemoglobina y lactato.Materiales y métodos: Se aisló ADN de 84 pacientes de cirugía cardiovascular para genotipificación por secuenciación de Sanger y se recolectaron características demográficas y clínicas.Resultados. La frecuencia del alelo T fue 0.066 (IC95%: 0.037-0.114). No hubo diferencias significativas en los niveles de hemoglobina y lactato preoperatorios, intraoperatorios y posoperatorios entre pacientes con alelo T y aquellos con alelo ancestral.Conclusión. La frecuencia del alelo T fue menor que la esperada, de acuerdo con otros estudios en poblaciones similares de voluntarios sanos y no mostró diferencias significativas con algunas poblaciones asiáticas, ni con un grupo de pacientes con infarto agudo de miocardio. Parece que la genotipificación de rs11549465 en pacientes de cirugía cardiovascular no representó un método de estratificación de riesgo de anemia en este grupo. Introduction: Perioperative anemia is a common complication of cardiovascular surgery. Patients who present the T allele of the HIF-1α rs11549465 polymorphism may have altered hemoglobin and lactate levels before, during and after surgery, compared to the wild-type allele, due to an increased stability of HIF-1 α caused by this allele.Objective: To describe the frequency of the T allele in patients scheduled for cardiovascular surgery, and its relationship with hemoglobin and lactate levels.Materials and methods: DNA was isolated from 84 cardiovascular surgery patients for genotyping by Sanger sequencing. Demographic and clinical characteristics were collected.Results: The frequency of the T allele was 0.066 (95%CI: 0.037-0.114). No significant differences were observed in preoperative, intraoperative, and postoperative hemoglobin and lactate levels between patients with the T allele and those with the wild-type allele.Conclusion: The frequency of the T allele is lower than expected according to other studies in healthy volunteers. No significant differences were observed in some Asian populations, nor in a group of acute myocardial infarction patients. Apparently, rs11549465 genotyping in cardiovascular surgery patients is not a valid risk stratification method for anemia in this group.

Resumen Introducción. A pesar de los importantes avances en el entendimiento de la patofisiología de la sepsis, la mortalidad que genera sigue siendo alta. Objetivo. Describir el estado del arte de los biomarcadores moleculares propuestos hasta el momento como potenciales marcadores para el diagnóstico y pronóstico de sepsis, sepsis grave y choque séptico. Materiales y métodos. Se analizaron los registros de los últimos 14 años que se encontraban en PubMed, en The New England Journal of Medicine (NEJM) y en Illinois Automatic Computer (ILLIAC) con los términos sepsis, genetic polymorphisms, genetic variation y molecular marker. Se clasificaron los artículos por año de publicación y solo se tuvieron en cuenta los publicados durante los últimos 10 años. Resultados. La búsqueda arrojó 3 370 referencias que cubren más de 30 genes con polimorfismos genéticos que pueden ser empleados como potenciales marcadores de polimorfismos. Estos fueron evaluados para su uso en las diferentes manifestaciones de sepsis, su diagnóstico y progresión. Se describen 20 genes marcadores: cuatro asociados con bacteremia (TLR-1, TLR-2, Proteína C y Selectina-E), nueve con sepsis (IL-1B, IL-1A, IL-6, TNF-a, TLR-1, MBL-1, Hsp70, PAI-1 y MIF-1), siete con sepsis grave (IL-1RN, IL-10, TNF-a, CD14, TREM-1, Caspasa 12 y DEFB-1), cinco con choque séptico (TNF-B, TLR-4, Hsp70, MBL-1 y CD14 ) y tres con disfunción multiorgánica (TLR-1,PAI-1 y Proteína C). Conclusión. Los polimorfismos genéticos, en su mayoría, han sido probados clínicamente como marcadores de diagnóstico y pronóstico en la sepsis con resultados prometedores por la alta especificidad y sensibilidad en la práctica clínica. Abstract Introduction: Despite important progress in the understanding of the pathophysiology of sepsis, the mortality rates caused by this condition remain high. Objective: To describe the state of the art on molecular biomarkers proposed as potential markers for the diagnosis and prognosis of sepsis, severe sepsis and septic shock. Materials and methods: The terms sepsis, genetic polymorphisms, genetic variation and molecular marker were analyzed in the records of the last 14 years of PubMed, the New England Journal of Medicine (NEJM) and Illinois Automatic Computer (ILLIAC). The papers were classified by year of publication; only those published within the last 10 years were taken into account. Results: The search yielded 3390 references covering more than 30 genes with genetic polymorphisms that can be used as potential polymorphism markers. They were assessed for use in different manifestations, diagnosis and progression of sepsis. Twenty genetic markers are described: four associated with bacteremia (TLR-1, TLR-2, Protein C and Selectin-E), nine with sepsis (IL-1B, IL-1A, IL-6, TNF-a, TLR-1, MBL-1, Hsp70, PAI-1 and MIF-1), seven with severe sepsis (IL-1RN, IL-10, TNF-a, CD14, TREM-1, Caspase 12 and DEFB-1), five with septic shock (TNF-B, TLR-4, Hsp70, MBL-1 and CD14 ), and three with multiorgan dysfunction (TLR-1, PAI-1 and Protein C). Conclusion: In general, genetic polymorphisms have been clinically tested as diagnostic and prognostic markers of sepsis with promising results due to the high specificity and sensitivity of the clinical practice.

Given the importance of the production of ruminants, it is necessary to investigate the genetic variants associated with the traits of economic interest in these animals, as well as the biology underlying the genotype-phenotype associations. To conduct these associations, a widely used strategy is to perform genome-wide association studies (GWAS). The GWAS must have the support of adequate quality control (QC), to then identify the associations between genetic markers type SNP and phenotypes. Additionally, the biological contextualization of these associations starts from the annotation of the genes close to the associated markers. Currently, there are several tools, including R libraries, to perform these analyses. However, it is necessary to develop a tool that allows unifying the three main steps (QC, GWAS, and annotation) for species other than human. For the above, the present work developed a methodology that unified the three mentioned steps in the R environment. The generated code was submitted for publication and is freely available in the repository https://github.com/bojusemo/Diploid-GWAS. The code was tested in two populations of ruminants, the Colombian Creole Hair Sheep and Simmental cattle. In these populations, the SNPs with low quality were removed, there was no detected population stratification, and no samples were removed for low quality. The SNP OAR26_10469468.1 was associated with the meat tenderness of Colombian Creole hair sheep. This SNP is in the gene TENM3. TENM3 protein has two domains with functions associated with meat tenderness in cattle and pigs. The SNP BovineHD4100012055 was associated with birth weight in Simmental. The closest gene to this SNP is the olfactory receptor 52E8-like, which is a member of the protein family G protein-coupled receptor (GPCR). GPCR has associated with birth weight in humans. Six markers were associated with 305-day milk yield in Simmental. Neither the closest genes of these markers nor their protein domains have been reported as associated with milk production. Resumen: Dada la importancia que tiene la producción de rumiantes, es necesario investigar las variantes genéticas asociadas a las características de interés comercial de dichos animales, así como la biología subyacente a esas asociaciones genotipo-fenotipo. Para hacer dichas asociaciones, una estrategia ampliamente utilizada es realizar estudios de asociación del genoma completo (GWAS). Los GWAS deben partir de un filtro adecuado de la información de las variables y de los individuos, denominado control de calidad (QC), para luego identificar las asociaciones entre marcadores genéticos tipo SNP y los fenotipos. Por su parte, la contextualización biológica de estas asociaciones parte de la anotación de los genes cercanos a los marcadores asociados. Para realizar estos análisis, actualmente hay varias herramientas, incluidas librerías de R. Sin embargo, falta desarrollar una herramienta que permita unificar los tres principales pasos (QC, GWAS y anotación) para datos de especies distintas al humano en R. Por lo anterior, el presente trabajo desarrolló una metodología que unificó en el entorno de R los tres pasos mencionados. El código generado se sometió a publicación y se encuentran disponibles de manera libre en el repositorio https://github.com/bojusemo/Diploid-GWAS. El código fue probado en dos poblaciones de rumiantes, el Ovino de Pelo Criollo Colombiano y los bovinos Simmental. En estas poblaciones, se eliminaron los SNPs con una baja calidad, no se detectó estratificación poblacional y no se eliminaron muestras por baja calidad. El SNP OAR26_10469468.1 estuvo asociado con la terneza de la carne del Ovino de Pelo Criollo Colombiano. Éste SNP está en el gen TENM3. La proteína TENM3 tiene dos dominios con funciones asociadas con la terneza de la carne en bovinos y porcinos. El SNP BovineHD4100012055 estuvo asociado con el peso al nacimiento de Simmental. El gen más cercano a este SNP es el olfactory receptor 52E8-like, que pertenece a la familia de proteínas G protein-coupled receptor (GPCR). Se ha reportado asociación entre GPCR y el peso al nacimiento en humanos. Seis marcadores estuvieron asociados a la producción de leche a los 305 días en Simmental. Ni los genes más cercanos a los marcadores, ni los dominios de las proteínas han sido reportados como asociados con la producción de leche. Maestría

Objective.The goal of this study was to determine the accuracy and bias of direct genomic values (DGV) using imputed genotypes at medium density in yield- and reproduction-related traits for Holstein cattle from Antioquia, Colombia.Materials and Methods.A total of 31 animals were genotyped with the Illumina BovineLD chip, 64 with Illumina BovineSNP50v2 and 48 with Illumina BovineHD. Two SNP panels (6K and 40K) were imputed to a density of 44K using the FINDHAP.f90 v4 program. The effects of the SNPs were estimated using the Bayes C method, using low-density (6K) genotypes as well as medium-density imputed genotypes (44_imputed). The accuracy and bias of the DGVs were determined by cross-validation. The evaluated traits were: milk yield (MY), percentage of protein (PP), percentage of fat (PF), somatic cell score (SCS), calving interval (CI) and open days (OD).Results.When using the 6K panel, the accuracy values for DGV (rpDGV;EBV) in all the studied traits ranged from 0.19 to 0.24, and the bias (bDGV;EBV) from 0.03 to 0.16. In contrast, using the 44K_imputed panel generated higher accuracy values ranging from 0.24 to 0.33 and a bias ranging from 0.03 to 0.26.Conclusions.The accuracy of prediction the DGV was higher with genotypes imputed to medium densities when compared to the accuracy of prediction obtained using low-density genotypes. Therefore, in this study it is concluded that the imputation of genotypes is very useful, because it improves the reliability of the genomic evaluation., Objetivo.Determinar la precisión y el sesgo de predicción de valores genómicos directos (VGD) usando genotipos imputados a densidad media, en características productivas y reproductivas en ganado Holstein de Antioquia, Colombia.Materiales y métodos.Fueron genotipificados 31 animales con el chip Illumina BovineLD, 64 con el chip Illumina BovineSNP50v2 y 48 con el chip Illumina BovineHD. La imputación se realizó usando dos paneles de SNPs (6K y 40K) a una densidad 44K, usando el programa FINDHAP.f90 v4. Los efectos de los SNPs fueron estimados mediante el método bayes_C, usando genotipos de baja densidad (6K) y genotipos imputados a una densidad media (44_imputado). La precisión y el sesgo de los VGDs fueron determinados mediante validación cruzada. Las características evaluadas fueron: producción de leche (PL), porcentaje de proteína (PRO), porcentaje de grasa (GRA), puntaje de células somáticas (SCS), intervalo entre partos (IEP) y días abiertos (DA).Resultados.Las precisiones de VGD (rpVGD;EBV) en todas las características evaluadas oscilaron entre 0.19 y 0.24 y el sesgo (bVGD;EBV) entre 0.03 y 0.16 cuando se usó el panel 6K y usando el panel 44K_imputado las precisiones fueron mayores, oscilado entre 0.24 y 0.33 y sesgo entre 0.03 y 0.26.Conclusiones.La precisión de predicción de los VGDs fue mayor cuando se usaron genotipos imputados a densidad media, en comparación con la precisión de predicción obtenida empleando genotipos de baja densidad. Por lo cual, en este estudio se concluye que la imputación de genotipos es muy útil dado que aumenta la confiabilidad de la evaluación genómica.