A structural variant at ASIP associated with the darkness of hair coat is found in multiple zebu cattle populations.

A structural variant (SV) in the agouti signaling protein gene (ASIP), namely ASIP-SV1, has been found to strongly correlate with the darkness of hair coat in specific regions of the body of bulls from the zebu (Bos indicus) Nellore breed. Here we visually analyzed the whole-genome sequence of zebu and taurine (Bos taurus) cattle to elucidate the extent of spread of ASIP-SV1 in different cattle populations. Of 216 sequences analyzed, 63 zebu (45.9%) and five taurine (6.3%) animals had at least one copy of ASIP-SV1. Four of the taurine animals presenting the SV were Romagnola cattle, a breed with history of zebu introgression. The remaining taurine animal was a Simmental, a breed frequently used in crossbreeding. These data provide evidence that ASIP-SV1 is commonly found in zebu populations, in addition to taurine animals with zebu admixture.

Methylome Patterns of Cattle Adaptation to Heat Stress.

Heat stress has a detrimental impact on cattle health, welfare and productivity by affecting gene expression, metabolism and immune response, but little is known on the epigenetic mechanisms mediating the effect of temperature at the cellular and organism level. In this study, we investigated genome-wide DNA methylation in blood samples collected from 5 bulls of the heat stress resilient Nellore breed and 5 bulls of the Angus that are more heat stress susceptible, exposed to the sun and high temperature-high humidity during the summer season of the Brazilian South-East region. The methylomes were analyzed during and after the exposure by Reduced Representation Bisulfite Sequencing, which provided genome-wide single-base resolution methylation profiles. Significant methylation changes between stressful and recovery periods were observed in 819 genes. Among these, 351 were only seen in Angus, 366 were specific to Nellore, and 102 showed significant changes in methylation patterns in both breeds. KEGG and Gene Ontology (GO) enrichment analyses showed that responses were breed-specific. Interestingly, in Nellore significant genes and pathways were mainly involved in stress responses and cellular defense and were under methylated during heat stress, whereas in Angus the response was less focused. These preliminary results suggest that heat challenge induces changes in methylation patterns in specific loci, which should be further scrutinized to assess their role in heat tolerance.

Reparación Directa y Conflicto Armado Interno: la Constitucionalización de la Responsabilidad Extracontractual del Estado / Direct Reparation and Internal Armed Conflict: Constitutionalization of Tort Liability of the State / Reparação Direta e Conflito Armado Interno: a Constitucionalização da Responsabilidade Ilícita do Estado

Resumen Introducción: En materia de responsabilidad extracontractual del Estado, los procesos de reparación directa que se han derivado de hechos con ocasión al Conflicto Armado Interno, en adelante -CAI- han generado cambios en las categorías de protección que se han ido transformando especialmente desde que se reconoce la existencia del CAI. Objetivo: el principal objetivo de esta investigación está articulado a determinar cuáles son las condiciones que se han valorado por parte del Consejo de Estado para establecer la adecuación frente a los títulos de imputación y asimismo, las condiciones de interpretación de las categorías del daño antijurídico y la responsabilidad del Estado. Materiales y Métodos: El estudio fue delimitado a partir de la revisión documental de una elección aleatoria de sentencias del Consejo de Estado tomadas de forma no probabilística a través de las categorías de los títulos de imputación que se presentaron en una reconstrucción cronológica donde el eje referencia se contrastó en una dimensión analítica del reconocimiento del CAI. Resultados: el estudio evidenció cómo entre los diferentes títulos de imputación aplicables a hechos del CAI existen parámetros que evidencian una transición de omisión institucional que permitía un margen de la concepción del daño antijurídico en un sentido amplio, hacia un margen más limitado fundamentado en un desarrollo más riguroso del principio de legalidad. Conclusiones: La declaración del CAI tuvo una gran incidencia en la forma como se desarrolló la responsabilidad extracontractual del Estado, que al disponer de nuevas categorías de protección generó con ello más seguridad jurídica, pero, que a su vez limitó interpretaciones amplias del daño antijurídico.

Abstract Introduction: In matters of extracontractual liability of the State, the processes of direct reparation that have been derived from facts on the occasion of the CAI have generated changes in the categories of protection that have been transforming especially since the existence of the CAI is recognized. Objective: The main objective of this research is to determine which are the conditions that have been assessed by the Council of State to establish the adequacy of the title of imputation and the conditions of interpretation of the categories of antijuridical damage and the responsibility of the State. Materials and Methods: The study was delimited from the documentary review of a random selection of sentences of the Council of State taken in a non-probabilistic way through the categories of the titles of imputation that were presented in a chronological reconstruction where the reference axis was contrasted in an analytical dimension of the recognition of the CAI. Results: the study evidenced how among the different titles of imputation applicable to facts of the internal armed conflict there are parameters that evidence a transition from institutional omission that allowed a margin of the conception of the antijuridical damage wide towards a more limited margin based on a more rigorous development of the principle of legality. Conclusions: The declaration of the internal armed conflict had a great impact on the way tort liability was developed, which by providing new categories of protection generated more legal certainty but limited broad interpretations of tort.

Resumo Introdução: Em matéria de responsabilidade extracontratual do Estado, os processos de reparação direta que foram derivados de fatos por ocasião da CAI geraram mudanças nas categorias de proteção que têm se transformado especialmente desde que a existência da CAI foi reconhecida. Objetivo: O principal objetivo desta pesquisa é determinar as condições que foram avaliadas pelo Conselho de Estado para estabelecer a adequação do título de imputação e as condições de interpretação das categorias de danos antijurídicos e a responsabilidade do Estado. Materiais e Métodos: O estudo foi delimitado a partir da revisão documental de uma seleção aleatória de julgamentos do Conselho de Estado tomados de forma não-probabilística através das categorias dos títulos de imputação que foram apresentados em uma reconstrução cronológica onde o eixo de referência foi contrastado em uma dimensão analítica do reconhecimento do CAI. Resultados: o estudo evidenciou como entre os diferentes títulos de imputação aplicáveis aos fatos do conflito armado interno existem parâmetros que evidenciam uma transição da omissão institucional que permitiu uma margem ampla da concepção de dano anti-jurídico para uma margem mais limitada baseada em um desenvolvimento mais rigoroso do princípio da legalidade. Conclusões: A declaração do conflito armado interno teve um grande impacto na forma como a responsabilidade extracontratual foi desenvolvida, o que ao proporcionar novas categorias de proteção gerou maior segurança jurídica, mas limitou interpretações amplas dos danos não judiciais.

Growth Rate and Acceleration Analysis of the COVID-19 Pandemic Reveals the Effect of Public Health Measures in Real Time.

Background: Ending the COVID-19 pandemic is arguably one of the most prominent challenges in recent human history. Following closely the growth dynamics of the disease is one of the pillars toward achieving that goal. Objective: We aimed at developing a simple framework to facilitate the analysis of the growth rate (cases/day) and growth acceleration (cases/day2) of COVID-19 cases in real-time. Methods: The framework was built using the Moving Regression (MR) technique and a Hidden Markov Model (HMM). The dynamics of the pandemic was initially modeled via combinations of four different growth stages: lagging (beginning of the outbreak), exponential (rapid growth), deceleration (growth decay), and stationary (near zero growth). A fifth growth behavior, namely linear growth (constant growth above zero), was further introduced to add more flexibility to the framework. An R Shiny application was developed, which can be accessed at https://theguarani.com.br/ or downloaded from https://github.com/adamtaiti/SARS-CoV-2. The framework was applied to data from the European Center for Disease Prevention and Control (ECDC), which comprised 3,722,128 cases reported worldwide as of May 8th 2020. Results: We found that the impact of public health measures on the prevalence of COVID-19 could be perceived in seemingly real-time by monitoring growth acceleration curves. Restriction to human mobility produced detectable decline in growth acceleration within 1 week, deceleration within ~2 weeks and near-stationary growth within ~6 weeks. Countries exhibiting different permutations of the five growth stages indicated that the evolution of COVID-19 prevalence is more complex and dynamic than previously appreciated. Conclusions: These results corroborate that mass social isolation is a highly effective measure against the dissemination of SARS-CoV-2, as previously suggested. Apart from the analysis of prevalence partitioned by country, the proposed framework is easily applicable to city, state, region and arbitrary territory data, serving as an asset to monitor the local behavior of COVID-19 cases.

Single-Nucleotide Polymorphism Variations Associated With Specific Genes Putatively Identified Enhanced Genetic Predisposition for 305-Day Milk Yield in the Girolando Crossbreed.

Milk production phenotypes are the main focus of genetic selection in dairy herds, and although there are many genes identified as related to the biology of these traits in pure breeds, little is known about crossbreed animals. This study aimed to identify potential genes associated with the 305-day milk yield in 337 crossbreed Gir × Holstein (Girolando) animals. Milk production records were genotyped for 45,613 single-nucleotide polymorphisms (SNPs). This dataset was used for a genome-wide association study (GWAS) using the 305-day milk yield adjusted for the fixed effects of herd and year and linear and quadratic effects of age at calving (in days) and calving factor averaged per animal. Genes within the significant SNPs were retrieved from the Bos taurus ARS-UCD1.2 assembly (bosTau9) for gene ontology analysis. In summary, the GWAS identified 52 SNPs associated [p ≤ 10-4, false discovery rate (FDR) = 8.77%] with milk production, including NUB1 and SLC24A2, which were previously described as related to milk production traits in cattle. The results suggest that SNPs associated mainly with NUB1 and SLC24A2 could be useful to understand milk production in Girolando and used as predictive markers for selecting genetic predisposition for milk yield in Girolando.

Valor predictivo de proteína C reactiva y albúmina en la expulsión de litos ureterales de 6-10 mm del tercio inferior / Predictive Value of C-reactive Protein and Albumin in the Expulsion of Ureteral Stones (6-10 mm) from the Lower Third

Introducción La litiasis ureteral es responsable del 20% de casos de urolitiasis, el cólico renal afecta negativamente la calidad de vida, el mayor dilema es el elegir entre medidas conservadoras y cirugía. La mayoría de los litos ureterales de tercio distal menor de 6mm, pueden pasar espontáneamente con terapia conservadora. Sin embargo, ella se asocia a incomodidad, infecciones y ausencia laboral. La proteína C Reactiva (PCR) se ha utilizado como predictor en la expulsión de esos litos, además se introduce el uso de la albúmina como nuevo marcador de predicción. Objetivo El objetivo es analizar el valor predictivo de PCR y albúmina para la expulsión de litos ureterales de tercio inferior de 6­10 mm. Métodos Se realizó un estudio prospectivo en pacientes que presentaron cólico renal secundario a litiasis ureteral distal 6­10 Mm, los cuales recibieron tratamiento médico expulsivo durante 4 semanas, hasta la expulsión del lito o la necesidad de tratamiento quirúrgico en que se determinó punto de corte de PCR y albúmina por medio de una curva COR. Resultados 78 pacientes se enrolaron en el estudio, el paso espontáneo fue de 55,1% y el restante requirió de intervención quirúrgica, el punto de corte para PCR fue 5,95 mg/L y de 2,75 g/dl para albúmina. Conclusión El PCR es un parámetro predictivo en la expulsión de litos ureterales de tercio inferior en pacientes muy seleccionados. Se obtiene el siguiente punto de corte para predecir la eliminación del lito (5,95 mg/L) y se propone la albúmina como un nuevo parámetro bioquímico.

Introduction Ureteral stones is responsible for 20% of cases of urolithiasis, renal colic negatively affects quality of life, the main dilemma is choosing between conservative measures and surgery. Most ureteral stones of the distal third smaller than 6 mm can pass spontaneously with conservative therapy. However, this is associated with discomfort, infections. C Reactive protein (CRP) has been used as a predictor in the expulsion of these stones, and the use of albumin as a new marker of prediction is also introduced. Objective The objective is to analyze the predictive value of CRP and albumin for the expulsion of ureteral stones of the lower third of 6­10 mm Methods A prospective study was performed in patients who presented renal colic secondary to distal ureteral lithiasis 6­10 mm and who received medical expulsive treatment for 4 weeks, until the expulsion of the stone or the need for surgical treatment, PCR cut off point was determined and albumin by means of a ROC curve. Results 78 patients enrolled in the study, spontaneous passage was 55.1% and the remaining required surgical intervention, the cut-off point for PCR was 5.95 mg/L and 2.75 g/dl for albumin. Conclusion CRP is a predictive parameter in the expulsion of lower third ureteral stones in highly selected patients. The following cut off point is obtained to predict the elimination of lithium (5.95 mg/L) and albumin is proposed as a new biochemical parameter.

Evaluación y manejo del riesgo cardiovascular en infección por VIH. Consenso de expertos ACIN / Evaluation and management of cardiovascualr risk in VIH infection: Expert consensus of ACIN (Colombian Association of Infectious Diseases)

Los pacientes con infección por VIH tienen una mayor incidencia de eventos cardiovasculares en comparación con la población general; los factores que contribuyen al incremento del riesgo de eventos cardiovasculares son la prevalencia de factores de riesgo cardiovascular tradicionales (FRCV), la infección por VIH que condiciona tanto un proceso de inflamación crónica como alteración de la función endotelial y la exposición a los antirretrovirales. Los factores que deben ser objeto de intervención son los FRCV tradicionales, en especial la alta tasa de fumadores entre este grupo de pacientes, la tamización y tratamiento de HTA, el síndrome metabólico y el acceso temprano a la terapia antirretroviral con medicamentos con mayor perfil de seguridad . Esta guía pretende proveer información y recomendaciones en el ámbito nacional acerca de la relación entre la infección por VIH/SIDA (Síndrome de Inmunodeficiencia Adquirida), uso de antirretrovirales y riesgo cardiovascular.

Patients with VIH infection have greater risk for cardiovascular diseases compared to general population. Risk factors that increase the frequency of cardiovascular events are: presence of cardiovascular traditional risk factors, chronic inflammation by HIV that impairs endothelial function and the exposure to antiretrovirals. The factors that should be the target for intervention are the traditional know cardiovascular factors such, especially high rate of smokers, screening and treatment for hypertension, metabolic syndrome and early access to HAART. The present guidelines provides information about the use of antiretrovirals in patients with HIV and its relation with cardiovascular risk.

Association of Copy Number Variation at Intron 3 of HMGA2 With Navel Length in Bos indicus.

Navel injuries caused by friction against the pasture can promote infection, reproductive problems and costly treatments in beef cattle raised in extensive systems. A haplotype-based genome-wide association study (GWAS) was performed for visual scores of navel length at yearling in Nellore cattle (Bos indicus) using data from 2,016 animals and 503,088 single nucleotide polymorphism (SNP) markers. The strongest signal (p = 1.01 × 10-9) was found on chromosome 5 spanning positions 47.9-48.2 Mbp. This region contains introns 3 and 4 and exons 4 and 5 of the high mobility group AT-hook 2 gene (HMGA2). Further inspection of the region with whole genome sequence data of 21 Nellore bulls revealed correlations between counts of the significant haplotype and copy number gains of a ∼6.2 kbp segment of intron 3 of HMGA2. Analysis of genome sequences from five African B. indicus and four European Bos taurus breeds revealed that the copy number variant (CNV) is indicine-specific. This intronic CNV was then validated through quantitative polymerase chain reaction (qPCR) using Angus animals as copy neutral controls. Importantly, the CNV was not detectable by means of conventional SNP-based GWAS or SNP probe intensity analyses. Given that HMGA2 affects the expression of the insulin-like growth factor 2 gene (IGF2) together with the pleomorphic adenoma gene 1 (PLAG1), and that the latter has been repeatedly shown to be associated with quantitative traits of economic importance in cattle, these findings highlight the emerging role of variants impacting the insulin-like growth factor pathway to cattle breeding.

Genome-wide association study using haplotype alleles for the evaluation of reproductive traits in Nelore cattle.

Zebu cattle (Bos taurus indicus) are highly adapted to tropical regions. However, females reach puberty after taurine heifers, which affects the economic efficiency of beef cattle breeding in the tropical regions. The aims of this study were to establish associations between the haplotype alleles of the bovine genome and age at first calving (AFC) in the Nelore cattle, and to identify the genes and quantitative trait loci (QTL) related to this phenotype. A total of 2,273 Nelore cattle (995 males and 1,278 females) genotyped using the Illumina BovineHD BeadChip were used in the current study. The association analysis included females with valid first calving records as well as open heifers. Linkage disequilibrium (LD) analysis among the markers was performed using blocks of 5, 10, and 15 markers, which were determined by sliding windows shifting one marker at a time. Then, the haplotype block size to be used in the association study was chosen based on the highest r2 average among the SNPs in the block. The five HapAlleles most strongly associated with the trait (top five) were considered as significant associations. The results of the analysis revealed four genomic regions related to AFC, which overlapped with 20 QTL of the reproductive traits reported previously. Furthermore, there were 19 genes related to reproduction in those regions. In conclusion, the use of haplotypes allowed the detection of chromosomal regions associated with AFC in Nelore cattle, and provided the basis for elucidating the mechanisms underlying this trait.

Systemic oxidative stress in Suffolk and Santa Ines sheep experimentally infected with Haemonchus contortus.

The mechanisms responsible for the imbalance between oxidants and antioxidants in sheep infected with Haemonchus contortus are not well established. This study aimed to prove the hypothesis that oxidative stress occurring during infection by H. contortus varies according to breed, and that the parasite burden correlates with hypoalbuminaemia and anaemia. Thus, after deworming and confirming the absence of infection, two different sheep breeds, Suffolk (n = 15) and Santa Ines (n = 22), were orally inoculated with a single dose of 5,000 L3 of H. contortus. The egg counts per gram of faeces (EPG), packed cell volume (PCV) and concentrations of several plasma markers of oxidative stress (lipid peroxidation, albumin, uric acid, total bilirubin, total antioxidant capacity [TAC], total oxidant concentration [TOC] and the oxidative stress index [OSI]) were quantified before (control group) and during the experimental infection (28, 34 and 42 days post-inoculation). In both breeds, TOC increased at 28 days and TAC increased at 42 days. In Suffolk sheep, there was a positive correlation of EPG with oxidant components (28 days) and a negative correlation of EPG with PCV (42 days). In Santa Ines sheep, there was a positive correlation of EPG with bilirubin (r = 0.492; p = 0.020). H. contortus infection caused oxidative stress, which varied according to the breed. Parasite burden was not associated with hypoalbuminaemia, whereas there was a negative correlation with PCV. This research provides the first evidence that the antioxidant status contributes more to the resilience to H. contortus in Santa Ines sheep compared to Suffolk sheep.

[Lethality analysis in patients with tuberculosis diagnosis in a high complexity hospital in Cali, Colombia]. / Análisis de letalidad en pacientes con diagnóstico de tuberculosis en un centro de alta complejidad en Cali, Colombia.

Background In 2016 tuberculosis (TB) was considered the ninth leading cause of death worldwide and the leading cause of a single infectious agent, with approximately 1.6 million deaths worldwide and a lethality of 15%. Over 95% of cases and deaths are in developing countries like Colombia. AIM: To describe the sociodemographic and clinical characteristics of patients who died during TB treatment in a high complexity hospital in Cali, Colombia. METHODS: We conducted an analytic retrospective cohort during 2007-2016 in Fundación Valle del Lili. We included patients with TB diagnosis, who died during TB treatment. RESULTS: From 787 patients with TB, 69 died (8.8%). Fifty nine percent were male, the average of age was 51.9 years. There was diagnosis delay in 51% of the patients and 74% presented pulmonary TB. Sixty four percent 64 died in the first 30 days of the TB diagnosis and 61% of the deaths were attributable to TB. Twenty five percent of patients had TB/HIV coinfection. Elderly patients (> 65 years old) were associated with death in the first 30 days of TB diagnosis (p < 0,001). DISCUSSION: The lethality found in this study was higher than expected (8.8%), the majority of patients had serious comorbidities. Elderly patients were associated with early death. The main pathophysiological mechanism of death was septic shock caused by severe tuberculous pneumonia.

Genomic predictions combining SNP markers and copy number variations in Nellore cattle.

BACKGROUND: Due to the advancement in high throughput technology, single nucleotide polymorphism (SNP) is routinely being incorporated along with phenotypic information into genetic evaluation. However, this approach often cannot achieve high accuracy for some complex traits. It is possible that SNP markers are not sufficient to predict these traits due to the missing heritability caused by other genetic variations such as microsatellite and copy number variation (CNV), which have been shown to affect disease and complex traits in humans and other species. RESULTS: In this study, CNVs were included in a SNP based genomic selection framework. A Nellore cattle dataset consisting of 2230 animals genotyped on BovineHD SNP array was used, and 9 weight and carcass traits were analyzed. A total of six models were implemented and compared based on their prediction accuracy. For comparison, three models including only SNPs were implemented: 1) BayesA model, 2) Bayesian mixture model (BayesB), and 3) a GBLUP model without polygenic effects. The other three models incorporating both SNP and CNV included 4) a Bayesian model similar to BayesA (BayesA+CNV), 5) a Bayesian mixture model (BayesB+CNV), and 6) GBLUP with CNVs modeled as a covariable (GBLUP+CNV). Prediction accuracies were assessed based on Pearson's correlation between de-regressed EBVs (dEBVs) and direct genomic values (DGVs) in the validation dataset. For BayesA, BayesB and GBLUP, accuracy ranged from 0.12 to 0.62 across the nine traits. A minimal increase in prediction accuracy for some traits was noticed when including CNVs in the model (BayesA+CNV, BayesB+CNV, GBLUP+CNV). CONCLUSIONS: This study presents the first genomic prediction study integrating CNVs and SNPs in livestock. Combining CNV and SNP marker information proved to be beneficial for genomic prediction of some traits in Nellore cattle.

Análisis de letalidad en pacientes con diagnóstico de tuberculosis en un centro de alta complejidad en Cali, Colombia / Lethality analysis in patients with tuberculosis diagnosis in a high complexity hospital in Cali, Colombia

Resumen Introducción: En el 2016 la tuberculosis (TBC) fue considerada la novena causa de muerte en el mundo y la primera por un único agente infeccioso, con aproximadamente 1,6 millones de muertes y una letalidad de 15%. Más de 95% de los casos de mortalidad mundial se presentan en países en vía de desarrollo como Colombia. Objetivo: Describir las características sociodemográficas y clínicas de los pacientes que fallecieron durante el tratamiento antituberculoso en un centro de alta complejidad en Cali, Colombia. Métodos: Estudio analítico de cohorte retrospectiva, realizado entre 2007-2016 en la Fundación Valle del Lili. Se incluyeron pacientes con diagnóstico de TBC con seguimiento clínico, que fallecirron por cualquier causa. Resultados: De 787 pacientes diagnosticados con TBC, murieron 69 (8,8%). La mayoría de los fallecidos (59%) fueron hombres, edad promedio de 51,9 años. Hubo retraso diagnóstico en 51% de los pacientes y 75% presentaron TBC pulmonar. El 64% murió en los primeros 30 días posteriores al diagnóstico de TBC y 61% de las muertes fueron atribuibles a TBC. Co-infección TBC e infección por VIH se presentó en 23% de los casos. La edad avanzada (> 65 años) se asoció a muerte en menos de 30 días desde el diagnóstico de TBC (p < 0,001). Discusión: La letalidad encontrada es superior a lo esperado (8,8%); la mayoría de los pacientes fallecidos presentó co-morbilidades graves. La edad avanzada se asoció a muerte temprana. El principal mecanismo fisiopatológico de muerte por TBC en este estudio fue el choque séptico secundario a neumonía grave tuberculosa.

Background In 2016 tuberculosis (TB) was considered the ninth leading cause of death worldwide and the leading cause of a single infectious agent, with approximately 1.6 million deaths worldwide and a lethality of 15%. Over 95% of cases and deaths are in developing countries like Colombia. Aim: To describe the sociodemographic and clinical characteristics of patients who died during TB treatment in a high complexity hospital in Cali, Colombia. Methods: We conducted an analytic retrospective cohort during 2007-2016 in Fundación Valle del Lili. We included patients with TB diagnosis, who died during TB treatment. Results: From 787 patients with TB, 69 died (8.8%). Fifty nine percent were male, the average of age was 51.9 years. There was diagnosis delay in 51% of the patients and 74% presented pulmonary TB. Sixty four percent 64 died in the first 30 days of the TB diagnosis and 61% of the deaths were attributable to TB. Twenty five percent of patients had TB/HIV coinfection. Elderly patients (> 65 years old) were associated with death in the first 30 days of TB diagnosis (p < 0,001). Discussion: The lethality found in this study was higher than expected (8.8%), the majority of patients had serious comorbidities. Elderly patients were associated with early death. The main pathophysiological mechanism of death was septic shock caused by severe tuberculous pneumonia.

A PLAG1 mutation contributed to stature recovery in modern cattle.

The recent evolution of cattle is marked by fluctuations in body size. Height in the Bos taurus lineage was reduced by a factor of ~1.5 from the Neolithic to the Middle Ages, and increased again only during the Early Modern Ages. Using haplotype analysis, we found evidence that the bovine PLAG1 mutation (Q) with major effects on body size, weight and reproduction is a >1,000 years old derived allele that increased rapidly in frequency in Northwestern European B. taurus between the 16th and 18th centuries. Towards the 19th and 20th centuries, Q was introgressed into non-European B. taurus and Bos indicus breeds. These data implicate a major role of Q in recent changes in body size in modern cattle, and represent one of the first examples of a genomic sweep in livestock that was driven by selection on a complex trait.

Twenty-year follow-up of a familial case of PTH1R-associated primary failure of tooth eruption.

INTRODUCTION: Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder. METHODS: Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member. CONCLUSIONS: The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members.

Comparative analyses across cattle genders and breeds reveal the pitfalls caused by false positive and lineage-differential copy number variations.

We compared CNV region (CNVR) results derived from 1,682 Nellore cattle with equivalent results derived from our previous analysis of Bovine HapMap samples. By comparing CNV segment frequencies between different genders and groups, we identified 9 frequent, false positive CNVRs with a total length of 0.8 Mbp that were likely caused by assembly errors. Although there was a paucity of lineage specific events, we did find one 54 kb deletion on chr5 significantly enriched in Nellore cattle. A few highly frequent CNVRs present in both datasets were detected within genomic regions containing olfactory receptor, ATP-binding cassette, and major histocompatibility complex genes. We further evaluated their impacts on downstream bioinformatics and CNV association analyses. Our results revealed pitfalls caused by false positive and lineage-differential copy number variations and will increase the accuracy of future CNV studies in both taurine and indicine cattle.

Genome-wide CNV analysis reveals variants associated with growth traits in Bos indicus.

BACKGROUND: Apart from single nucleotide polymorphism (SNP), copy number variation (CNV) is another important type of genetic variation, which may affect growth traits and play key roles for the production of beef cattle. To date, no genome-wide association study (GWAS) for CNV and body traits in beef cattle has been reported, so the present study aimed to investigate this type of association in one of the most important cattle subspecies: Bos indicus (Nellore breed). RESULTS: We have used intensity data from over 700,000 SNP probes across the bovine genome to detect common CNVs in a sample of 2230 Nellore cattle, and performed GWAS between the detected CNVs and nine growth traits. After filtering for frequency and length, a total of 231 CNVs ranging from 894 bp to 4,855,088 bp were kept and tested as predictors for each growth trait using linear regression analysis with principal components correction. There were 49 significant associations identified among 17 CNVs and seven body traits after false discovery rate correction (P < 0.05). Among the 17 CNVs, three were significant or marginally significant for all the traits. We have compared the locations of associated CNVs with quantitative trait locus and the RefGene database, and found two sets of 9 CNVs overlapping with either known QTLs or genes, respectively. The gene overlapping with CNV100, KCNJ12, is a functional candidate for muscle development and plays critical roles in muscling traits. CONCLUSION: This study presents the first CNV-based GWAS of growth traits using high density SNP microarray data in cattle. We detected 17 CNVs significantly associated with seven growth traits and one of them (CNV100) may be involved in growth traits through KCNJ12.