New breeding location for the olrog`s gull <i>Larus atlanticus</i> in the province of Buenos Aires, Argentina

Se presenta información sobre una nueva colonia de Gaviota de Olrog (<i>Larus atlanticus</i>), una especie endémica de la Argentina y considerada internacionalmente como vulnerable. La colonia, visitada el 16 de noviembre de 2001, estaba localizada en un islote ubicado en el Canal Ancla (38°56'S, 62°11'O), unos 13 km al sudoeste de la ciudad de Punta Alta. Los nidos se hallaban distribuidos en cuatro grupos, de entre 17 y 238 nidos, totalizando 340 nidos activos. La colonia de Gaviota de Olrog se encontraba rodeada por nidos de Gaviota Cocinera (<i>Larus dominicanus</i>). La Gaviota de Olrog no se reprodujo en este islote en el año 1995. Debido a que esta especie puede cambiar de sitio de reproducción entre temporadas, futuros trabajos deberían evaluar su dinámica espacio-temporal de uso del hábitat.We present information on a new colony of Olrog`s Gull <i>Larus atlanticus</i>, endemic to Argentina and internationally considered as vulnerable. The colony, visited on November 16 2001, was on an islet located in the Canal Ancla (38°56'S, 62°11'O), 13 km southeast from Punta Alta. Nests were distributed in four groups of between 17-238 nests, add- ing to a total of 340 active nests. The Olrog?s Gull colony was located within a colony of Kelp Gulls (Larus dominicanus). Olrog`s Gulls did not breed in this islet during 1995. As this species may change colony sites between breeding seasons, future work should evaluate their spatial and temporal patterns of habitat use

Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs).MethodIn this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed.ResultsOur analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP.ConclusionsThrough WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Habitat and nest site characteristics of Olrog's Gull Larus atlanticus breeding at Bahía San Blas, Argentina

Olrog’s Gull Larus atlanticus is a vulnerable species endemic to the Argentine Atlantic coast. We present information on new breeding colonies, update information on known colonies, and describe habitat and nest site characteristics of Olrog’s Gulls breeding at Bahý´a San Blas, southern Buenos Aires Province, Argentina. Information was obtained during the 1998 breeding season. We recorded four colonies on islets, with a total population size of 305 pairs. Colonies were located on open ground, partly bordered by vegetation. The two colonies at Islote Arroyo Jabalý´ Oeste were located more than 150 m from the high tide line, while the two colonies at Banco Nordeste were placed only a few metres from the high tide mark (1–6 m). Most nests were located more than a metre away from low Atriplex patagonica bushes (20–30 cm high) and herbaceous species, although a few nests were a few cm from vegetation. Nests were built on vegetation debris, on low herbaceous vegetation, and on gravel and sand. All nests at the four colonies were built with vegetation debris, mainly Spartina densiflora and some Salicornia sp. Mean external and internal diameters of nests were 40.57 ± 5.14 and 19.71 ± 2.21 cm, respectively. Gulls nested in discrete groups at relatively high densities, which ranged between 0.62 and 1.1 nests/m2. Nest occupation and number of eggs per nest varied among colonies. Kelp Gulls Larus dominicanus were observed nesting in close proximity to all colonies. Further studies are needed to assess habitat partitioning between these two species, particularly considering that they nest in association at all breeding locations in coastal Argentina and that Kelp Gulls have shown an important population increase in recent decades.Fil: Yorio, Pablo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Rábano, Daniel. Centro de Estudios Ambientales para la Planificación y el Desarrollo; ArgentinaFil: Friedrich, Pablo. Centro de Estudios Ambientales para la Planificación y el Desarrollo; Argentin