Vertical variation in the amplitude of the seasonal isotopic content of rainfall as a tool to jointly estimate the groundwater recharge zone and transit times in the Ordesa and Monte Perdido National Park aquifer system, north-eastern Spain

The time series of stable water isotope composition relative to meteorological stations and springs located in the high mountainous zone of the Ordesa and Monte Perdido National Park are analyzed in order to study how the seasonal isotopic content of precipitation propagates through the hydrogeological system in terms of the aquifer recharge zone elevation and transit time. The amplitude of the seasonal isotopic composition of precipitation and the mean isotopic content in rainfall vary along a vertical transect, with altitudinal slopes for d18O of 0.9‰/km for seasonal amplitude and - 2.2‰/km for isotopic content. The main recharge zone elevation for the sampled springs is between 1950 and 2600 m·a.s.l. The water transit time for the sampled springs ranges from 1.1 to 4.5 yr, with an average value of 1.85 yr and a standard deviation of 0.8 yr. The hydrological system tends to behave as a mixing reservoir.Peer ReviewedPostprint (author's final draft

High resolution melting analysis for a rapid identification of heterozygous and homozygous sequence changes in the MUTYH gene

Background: MUTYH-associated polyposis (MAP) is an autosomal recessive form of intestinal polyposis predisposing to colorectal carcinoma. High resolution melting analysis (HRMA) is a mutation scanning method that allows detection of heterozygous sequence changes with high sensitivity, whereas homozygosity for a nucleotide change may not lead to significant curve shape or melting temperature changes compared to homozygous wildtype samples. Therefore, HRMA has been mainly applied to the detection of mutations associated with autosomal dominant or X-linked disorders, while applications to autosomal recessive conditions are less common. Methods: MUTYH coding sequence and UTRs were analyzed by both HRMA and sequencing on 88 leukocyte genomic DNA samples. Twenty-six samples were also examined by SSCP. Experiments were performed both with and without mixing the test samples with wild-type DNA. Results: The results show that all MUTYH sequence variations, including G > C and A > T homozygous changes, can be reliably identified by HRMA when a condition of artificial heterozygosity is created by mixing test and reference DNA. HRMA had a sensitivity comparable to sequencing and higher than SSCP. Conclusions: The availability of a rapid and inexpensive method for the identification of MUTYH sequence variants is relevant for the diagnosis of colorectal cancer susceptibility, since the MAP phenotype is highly variable

Vertical variation in the amplitude of the seasonal isotopic content of rainfall as a tool to jointly estimate the groundwater recharge zone and transit times in the Ordesa and Monte Perdido National Park aquifer system, north-eastern Spain

The time series of stable water isotope composition relative to meteorological stations and springs located in the high mountainous zone of the Ordesa and Monte Perdido National Park are analyzed in order to study how the seasonal isotopic content of precipitation propagates through the hydrogeological system in terms of the aquifer recharge zone elevation and transit time. The amplitude of the seasonal isotopic composition of precipitation and the mean isotopic content in rainfall vary along a vertical transect, with altitudinal slopes for d18O of 0.9‰/km for seasonal amplitude and - 2.2‰/km for isotopic content. The main recharge zone elevation for the sampled springs is between 1950 and 2600 m·a.s.l. The water transit time for the sampled springs ranges from 1.1 to 4.5 yr, with an average value of 1.85 yr and a standard deviation of 0.8 yr. The hydrological system tends to behave as a mixing reservoir.Peer Reviewe

Évaluation des ressources en eau des Pyrénées dans un contexte de changement climatique et stratégies d'adaptation

International audienceThe Pyrenees range is a transboundary region shared by Spain, France and Andorre. As many other mountainregions, it is excedentary in water resources that are used in a much larger area that includes important urbanconcentrations and productive rural areas. This territory is particularly vulnerable to the consequences of climatechange. The PIRAGUA project, funded by FEDER through the POCTEFA Programme of the EU, addresses theassessment of the hydrological cycle of the Pyrenees in the context of climate change. The goals of the projectare to unify and homogenise the existing information, prospect future scenarios, develop indicators of change, andpropose adaptation strategies with impact on the territory, with the ultimate goal of supporting investment aimedat adapting to climate change in relation to water resources. Thus, the project evaluates the components of thehydrological cycle and the water resources of the Pyrenees range in the recent past (1985-2015), and in futurescenarios (2030-2050). In addition, it will develop seven case studies about adaptation strategies at the local andregional scales, focusing on different socio-economic sectors, including hydropower production; sensitive head-water ecosystems; water and forests; irrigation agriculture; extreme events; tourism and areas of high ecologicalvalue; and multi-sector analysis, including the water-energy connection

High resolution melting analysis for a rapid identification of heterozygous and homozygous sequence changes in the MUTYH gene

Background: MUTYH-associated polyposis (MAP) is an autosomal recessive form of intestinal polyposis predisposing to colorectal carcinoma. High resolution melting analysis (HRMA) is a mutation scanning method that allows detection of heterozygous sequence changes with high sensitivity, whereas homozygosity for a nucleotide change may not lead to significant curve shape or melting temperature changes compared to homozygous wildtype samples. Therefore, HRMA has been mainly applied to the detection of mutations associated with autosomal dominant or X-linked disorders, while applications to autosomal recessive conditions are less common. Methods: MUTYH coding sequence and UTRs were analyzed by both HRMA and sequencing on 88 leukocyte genomic DNA samples. Twenty-six samples were also examined by SSCP. Experiments were performed both with and without mixing the test samples with wild-type DNA. Results: The results show that all MUTYH sequence variations, including G > C and A > T homozygous changes, can be reliably identified by HRMA when a condition of artificial heterozygosity is created by mixing test and reference DNA. HRMA had a sensitivity comparable to sequencing and higher than SSCP. Conclusions: The availability of a rapid and inexpensive method for the identification of MUTYH sequence variants is relevant for the diagnosis of colorectal cancer susceptibility, since the MAP phenotype is highly variable

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations