Fusarium graminearum and deoxynivalenol contamination in the durum wheat area of Argentina

Fusarium graminearum head blight of wheat is a destructive disease of the world's wheat-growing areas. This work was performed to analyze the distribution and contamination of deoxynivalenol (DON) and its relationship with F. graminearum kernel invasion in Argentina durum wheat area during two consecutive harvests. A total of 147 samples (cultivars and lines) of durum wheat from 5 locations of the major cropping area (Southern Buenos Aires Province) were analyzed. Percentage of F. graminearum kernel infection was evaluated following the blotter test (ISTA method) and fusarotoxins were analyzed by thin layer chromatography. None of the varieties and lines were free of F. graminearum infection. In the first harvest fungal invasion was very low. From 40 samples, 55% showed DON contamination but only 4 samples (10%) were higher than 2 ppm. In the second harvest, a crop year conducive to scab development, the highest level of F. graminearum kernel invasion observed was 42% on a sample from the humid area (eastern Buenos Aires Province) DON was detected in 47 (78.2%) of 60 samples analyzed and 19 (31.6%) showed levels of DON higher than those established in the guidelines in Canada and USA for food and feedstuff. In both years all locations situated in the humid area showed levels ranging from 0 to < 8 ppm. Within the durum wheat area differences among locations were found. This analysis indicates the need for more information on the problem and distribution of Fusarium mycotoxins in durum wheat grown in Argentina.Centro de Investigaciones de Fitopatologí

Fusarium graminearum and deoxynivalenol contamination in the durum wheat area of Argentina

Fusarium graminearum head blight of wheat is a destructive disease of the world's wheat-growing areas. This work was performed to analyze the distribution and contamination of deoxynivalenol (DON) and its relationship with F. graminearum kernel invasion in Argentina durum wheat area during two consecutive harvests. A total of 147 samples (cultivars and lines) of durum wheat from 5 locations of the major cropping area (Southern Buenos Aires Province) were analyzed. Percentage of F. graminearum kernel infection was evaluated following the blotter test (ISTA method) and fusarotoxins were analyzed by thin layer chromatography. None of the varieties and lines were free of F. graminearum infection. In the first harvest fungal invasion was very low. From 40 samples, 55% showed DON contamination but only 4 samples (10%) were higher than 2 ppm. In the second harvest, a crop year conducive to scab development, the highest level of F. graminearum kernel invasion observed was 42% on a sample from the humid area (eastern Buenos Aires Province) DON was detected in 47 (78.2%) of 60 samples analyzed and 19 (31.6%) showed levels of DON higher than those established in the guidelines in Canada and USA for food and feedstuff. In both years all locations situated in the humid area showed levels ranging from 0 to < 8 ppm. Within the durum wheat area differences among locations were found. This analysis indicates the need for more information on the problem and distribution of Fusarium mycotoxins in durum wheat grown in Argentina.Centro de Investigaciones de Fitopatologí

Actividad antifúngica de extractos vegetales empleados en la Medicina tradicional argentina

Se ensayó la actividad antifúngica in vitro de extractos hidroalcohólicos de plantas indígenas y exóticas empleadas en la Medicina Tradicional Argentina (MT), mediante el método del pocillo en la placa de agar, contra los hongos dermatofitos Microsporum canis, Trichophyton Mentagrophytes y T. rubrum y contra la levadura Candida albicans. De las 21 especies estudiadas, 19 mostraron actividad apreciablemente mayor que el nitrato de miconazol empleado como control. Entre las especies indígenas, Tabebuia impetiginosa (Mart. ex DC) Standley, conocida como “Lapacho” y Minthostachys verticillata (Griseb.) Epl., conocida como “Peperina” mostraron la mayor actividad. Otras especies indígenas como Aloysia triphylla (L’ Her.) Britton y Passiflora coerulea L. mostraron una actividad moderada.Fil: Prado, Héctor Juan. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica. Instituto Nacional de Medicamentos. Departamento de Microbiología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rizzo, Inés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica. Instituto Nacional de Medicamentos. Departamento de Microbiología e Inmunología; Argentin

Fusarium graminearum and deoxynivalenol contamination in the durum wheat area of Argentina

Fusarium graminearum head blight of wheat is a destructive disease of the world's wheat-growing areas. This work was performed to analyze the distribution and contamination of deoxynivalenol (DON) and its relationship with F. graminearum kernel invasion in Argentina durum wheat area during two consecutive harvests. A total of 147 samples (cultivars and lines) of durum wheat from 5 locations of the major cropping area (Southern Buenos Aires Province) were analyzed. Percentage of F. graminearum kernel infection was evaluated following the blotter test (ISTA method) and fusarotoxins were analyzed by thin layer chromatography. None of the varieties and lines were free of F. graminearum infection. In the first harvest fungal invasion was very low. From 40 samples, 55% showed DON contamination but only 4 samples (10%) were higher than 2 ppm. In the second harvest, a crop year conducive to scab development, the highest level of F. graminearum kernel invasion observed was 42% on a sample from the humid area (eastern Buenos Aires Province) DON was detected in 47 (78.2%) of 60 samples analyzed and 19 (31.6%) showed levels of DON higher than those established in the guidelines in Canada and USA for food and feedstuff. In both years all locations situated in the humid area showed levels ranging from 0 to < 8 ppm. Within the durum wheat area differences among locations were found. This analysis indicates the need for more information on the problem and distribution of Fusarium mycotoxins in durum wheat grown in Argentina.Centro de Investigaciones de Fitopatologí

STEM education: integrating photometry concepts into math class using technology

En este trabajo se presenta una actividad enmarcada en la Teoría Antropológica de lo Didáctico y en el enfoque de enseñanza STEM. La misma se realiza en el nivel secundario, habiendo sido adaptada de otra realizada en el nivel universitario, con el objetivo es vivenciar nuevas formas de hacer ciencia. Se propone investigar sobre una pregunta disparadora del área de la óptica, en especial de la fotometría. Para dar respuesta, se utiliza tecnología de bajo costo y al alcance de la mayoría de los jóvenes y docentes: dispositivos móviles y el software GeoGebra. Se describe la actividad y se presentan resultados. Finalmente se concluye que este estilo de iniciativa, en concordancia con las actuales tendencias de enseñanza y aprendizaje de las ciencias, es posible de desarrollar en cursos habituales de nivel secundario.In this paper we present an activity framed in the anthropological Theory of the Didactic and in the STEM teaching approach. The same is done at the secondary level, having been adapted from another realized at the university level, with the aim to experience new ways of doing science. It is proposed to investigate a triggering question of the area of optics, especially photometry. To respond, low cost and affordable technology is used for most young people and teachers: mobile devices and GeoGebra software. The activity is described and results are presented. Finally, it is concluded that this style of initiative, in accordance with the current trends of teaching and learning of the sciences, is possible to develop in secondary-level courses.Investigación en Metodologías Alternativas para la Enseñanza de las Ciencia

STEM education: integrating photometry concepts into math class using technology

En este trabajo se presenta una actividad enmarcada en la Teoría Antropológica de lo Didáctico y en el enfoque de enseñanza STEM. La misma se realiza en el nivel secundario, habiendo sido adaptada de otra realizada en el nivel universitario, con el objetivo es vivenciar nuevas formas de hacer ciencia. Se propone investigar sobre una pregunta disparadora del área de la óptica, en especial de la fotometría. Para dar respuesta, se utiliza tecnología de bajo costo y al alcance de la mayoría de los jóvenes y docentes: dispositivos móviles y el software GeoGebra. Se describe la actividad y se presentan resultados. Finalmente se concluye que este estilo de iniciativa, en concordancia con las actuales tendencias de enseñanza y aprendizaje de las ciencias, es posible de desarrollar en cursos habituales de nivel secundario.In this paper we present an activity framed in the anthropological Theory of the Didactic and in the STEM teaching approach. The same is done at the secondary level, having been adapted from another realized at the university level, with the aim to experience new ways of doing science. It is proposed to investigate a triggering question of the area of optics, especially photometry. To respond, low cost and affordable technology is used for most young people and teachers: mobile devices and GeoGebra software. The activity is described and results are presented. Finally, it is concluded that this style of initiative, in accordance with the current trends of teaching and learning of the sciences, is possible to develop in secondary-level courses.Investigación en Metodologías Alternativas para la Enseñanza de las Ciencia

STEM education: integrating photometry concepts into math class using technology

En este trabajo se presenta una actividad enmarcada en la Teoría Antropológica de lo Didáctico y en el enfoque de enseñanza STEM. La misma se realiza en el nivel secundario, habiendo sido adaptada de otra realizada en el nivel universitario, con el objetivo es vivenciar nuevas formas de hacer ciencia. Se propone investigar sobre una pregunta disparadora del área de la óptica, en especial de la fotometría. Para dar respuesta, se utiliza tecnología de bajo costo y al alcance de la mayoría de los jóvenes y docentes: dispositivos móviles y el software GeoGebra. Se describe la actividad y se presentan resultados. Finalmente se concluye que este estilo de iniciativa, en concordancia con las actuales tendencias de enseñanza y aprendizaje de las ciencias, es posible de desarrollar en cursos habituales de nivel secundario.In this paper we present an activity framed in the anthropological Theory of the Didactic and in the STEM teaching approach. The same is done at the secondary level, having been adapted from another realized at the university level, with the aim to experience new ways of doing science. It is proposed to investigate a triggering question of the area of optics, especially photometry. To respond, low cost and affordable technology is used for most young people and teachers: mobile devices and GeoGebra software. The activity is described and results are presented. Finally, it is concluded that this style of initiative, in accordance with the current trends of teaching and learning of the sciences, is possible to develop in secondary-level courses.Investigación en Metodologías Alternativas para la Enseñanza de las Ciencia

Peripheral changes in immune cell populations and soluble mediators after anti-PD-1 therapy in non-small cell lung cancer and renal cell carcinoma patients

Patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline samples, discriminant analysis revealed a combination of four variables that helped differentiate stable disease-response (SD-R) from progressive disease (PD) patients: augmented frequency of central memory CD4+ T cells and leukocyte count was associated with response while increased percentage of PD-L1+ natural killer cells and naïve CD4+ T cells was associated with lack of response. After therapy, differential changes between responders and non-responders were found in leukocytes, T cells and TIM-3+ T cells. Patients with progressive disease showed an increase in the frequency of TIM-3 expressing CD4+ and CD8+ T cells, whereas SD-R patients showed a decrease in these subsets. Our findings indicate that a combination of immune variables from peripheral blood (PB) could be useful to distinguish response groups in NSCLC and RCC patients treated with anti-PD-1 therapy. Frequency of TIM-3+ T cells showed differential changes after treatment in PD vs SD-R patients, suggesting that it may be an interesting marker for monitoring progression during therapy.Fil: Juliá, Estefanía Paula. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mandó, Pablo. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Rizzo, Manglio Miguel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cueto, Gerardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Tsou, Florencia. Instituto Alexander Fleming; ArgentinaFil: Luca, Romina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Pupareli, Carmen. Instituto Alexander Fleming; ArgentinaFil: Bravo, Alicia Inés. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Presidente Peron; ArgentinaFil: Astorino, Walter. Instituto Alexander Fleming; ArgentinaFil: Mordoh, José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Martín, Claudio. Instituto Alexander Fleming; ArgentinaFil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

COVID-19 Vaccination Responses with Different Vaccine Platforms in Patients with Inborn Errors of Immunity

Patients with inborn errors of immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data of humoral and cellular responses combination on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients (n = 118) and age-matched healthy controls (HC) (n = 37). B cell response was evaluated by measuring IgG anti-spike/receptor binding domain (S/RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T cell response was analyzed by IFN-γ secretion on S- or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry. No moderate/severe vaccine-associated adverse events were observed. Anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort (p < 0.05). Neutralizing antibodies were also significantly lower in the patient cohort than in age-matched HC (p < 0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. Moderna vaccines, which were mainly administered in the pediatric population, elicited a stronger humoral response in IEI patients, both in antibody titer and neutralization capacity, but the cellular immune response was similar between vaccine platforms. No difference in humoral response was observed between vaccinated patients with and without previous SARS-CoV-2 infection. In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers, and T cell-dependent cellular immunity with IFN-γ secreting cells. These findings may guide the recommendation for a vaccination with all the available vaccines in IEI patients to prevent COVID-19 disease.Fil: Erra, Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Uriarte, Ignacio. Universidad Nacional de Mar del Plata; Argentina. Hospital Interzonal Especializado Materno Infantil Don Victorio Tetamanti (hiemi Victorio Tetamanti) ; Gobierno de la Provincia de Buenos Aires;Fil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Paolini, María Virginia. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Seminario, Gisela. No especifíca;Fil: Fernández, Julieta Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Tau, Lorena. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Salud Pública; ArgentinaFil: Bernatowiez, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Moreira, Ileana. No especifíca;Fil: Vishnopolska, Sebastián Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rumbo, Martín. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Salud Pública; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cassarino, María Chiara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vijoditz, Gustavo. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: López, Ana Laura. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Curciarello, Renata. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Salud Pública; ArgentinaFil: Rodríguez, Diego. Universidad Nacional de Mar del Plata; Argentina. Hospital Interzonal Especializado Materno Infantil Don Victorio Tetamanti (hiemi Victorio Tetamanti) ; Gobierno de la Provincia de Buenos Aires;Fil: Rizzo, Gaston Pascual. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Salud Pública; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Ferreyra Compagnucci, Malena María. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Salud Pública; ArgentinaFil: Ferreyra Mufarregue, Leila Romina. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ibañez, Lorena Itatí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Docena, Guillermo H.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Salud Pública; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bezrodnik, Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Almejún, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation