Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis.

Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females).

National-scale remotely sensed lake trophic state from 1984 through 2020.

Lake trophic state is a key ecosystem property that integrates a lake's physical, chemical, and biological processes. Despite the importance of trophic state as a gauge of lake water quality, standardized and machine-readable observations are uncommon. Remote sensing presents an opportunity to detect and analyze lake trophic state with reproducible, robust methods across time and space.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model.

SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in amyotrophic lateral sclerosis.

Variants in the superoxide dismutase () gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has become clear that -linked ALS presents a highly variable age at symptom onset and disease duration. Here we describe an open access web tool for comparative phenotype analysis in ALS: https://sod1-als-browser.

Chemistry of surface water, precipitation, throughfall, leaves, sediment, soil, and air near a gold mining region in Peru.

Artisanal and small-scale gold mining (ASGM) is the primary global source of anthropogenic mercury (Hg) emissions and a large source of landscape change. ASGM occurs throughout the world, including in the Peruvian Amazon. This data set contains measurements of surface water, precipitation, throughfall, leaves, sediment, soil, and air samples from across the Madre de Dios region of Peru, in locations near and remote from ASGM.

Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis.

There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability.

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.

Objective: To identify the genetic variants associated with juvenile ALS.

Design, Setting, And Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation.

A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decay.

Loss of function (LoF) mutations in Optineurin can cause recessive amyotrophic lateral sclerosis (ALS) with some heterozygous LoF mutations associated with dominant ALS. The molecular mechanisms underlying the variable inheritance pattern associated with OPTN mutations have remained elusive. We identified that affected members of a consanguineous Middle Eastern ALS kindred possessed a novel homozygous p.

Shifting Patterns of Summer Lake Color Phenology in Over 26,000 US Lakes.

Lakes are often defined by seasonal cycles. The seasonal timing, or phenology, of many lake processes are changing in response to human activities. However, long-term records exist for few lakes, and extrapolating patterns observed in these lakes to entire landscapes is exceedingly difficult using the limited number of available in situ observations.

Generation of six induced pluripotent stem cell lines from patients with amyotrophic lateral sclerosis with associated genetic mutations in either FUS or ANXA11.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons, causing gradual paralysis, and resulting in death 3-5 years from diagnosis. ALS causative mutations have been identified in multiple genes, including Fused in sarcoma (FUS), and recently characterized Annexin A11 (ANXA11). We have derived induced pluripotent stem cell (iPSC) lines from six ALS patient lymphoblastoid cell lines, three with mutations in FUS (Q519E, R521H, R522G), and three with mutations in ANXA11 (G38R, D40G, R235Q).

Artificial lake expansion amplifies mercury pollution from gold mining.

Artisanal and small-scale gold mining (ASGM) is the largest global source of anthropogenic mercury emissions. However, little is known about how effectively mercury released from ASGM is converted into the bioavailable form of methylmercury in ASGM-altered landscapes. Through examination of ASGM-impacted river basins in Peru, we show that lake area in heavily mined watersheds has increased by 670% between 1985 and 2018 and that lakes in this area convert mercury into methylmercury at net rates five to seven times greater than rivers.

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures.

Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE).

Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies.

CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral sclerosis.

Frontotemporal dementia and amyotrophic lateral sclerosis are clinically and pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.

Publisher Correction: Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein.

To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses, we replicated known ALS genes including SOD1, NEK1 and FUS.

RRM adjacent TARDBP mutations disrupt RNA binding and enhance TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) presents with focal muscle weakness due to motor neuron degeneration that becomes generalized, leading to death from respiratory failure within 3-5 years from symptom onset. Despite the heterogeneity of aetiology, TDP-43 proteinopathy is a common pathological feature that is observed in >95% of ALS and tau-negative frontotemporal dementia (FTD) cases. TDP-43 is a DNA/RNA-binding protein that in ALS and FTD translocates from being predominantly nuclear to form detergent-resistant, hyperphosphorylated aggregates in the cytoplasm of affected neurons and glia.

ALSgeneScanner: a pipeline for the analysis and interpretation of DNA sequencing data of ALS patients.

Amyotrophic lateral sclerosis (ALS, MND) is a neurodegenerative disease of upper and lower motor neurons resulting in death from neuromuscular respiratory failure, typically within two years of first symptoms. Genetic factors are an important cause of ALS, with variants in more than 25 genes having strong evidence, and weaker evidence available for variants in more than 120 genes. With the increasing availability of next-generation sequencing data, non-specialists, including health care professionals and patients, are obtaining their genomic information without a corresponding ability to analyze and interpret it.

Striking phenotypic variation in a family with the P506S UBQLN2 mutation including amyotrophic lateral sclerosis, spastic paraplegia, and frontotemporal dementia.

Analysis of 226 exome-sequenced UK cases of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia identified 2 individuals who harbored a P497H and P506S UBQLN2 mutation, respectively (n = 0.9%). The P506S index case presented with behavioral variant frontotemporal dementia at the age of 54 years then progressed to ALS surviving 3 years.

Younger age of onset in familial amyotrophic lateral sclerosis is a result of pathogenic gene variants, rather than ascertainment bias.

Objective: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease of motor neurons with a median survival of 2 years. Familial ALS has a younger age of onset than apparently sporadic ALS. We sought to determine whether this younger age of onset is a result of ascertainment bias or has a genetic basis.