RNA science and its applications-a look toward the future: Albany, NY USA, November 3-4, 2011.

On November 3-4, 2011, the Symposium RNA Science and its Applications: A look toward the Future was held at the University at Albany-SUNY in the capital of New York State. Unique to this Symposium's format were panel discussions following each of the four platform sessions: RNA Technological Innovation: Analysis, Delivery, Nanotechnologies, IT; Infectious and other diseases: The future of small molecule intervention; RNA Discovery and Innovation: Cell and Molecular Biology; and Cancer and Neurological Disease: The future of small RNAs as therapeutics and tools of investigation. The meeting was organized by Thomas Begley, Marlene Belfort, Daniele Fabris, Melinda Larsen, Pan T.

Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group.

Disease-related and genetic correlates of psychotic symptoms in Parkinson's disease.

Our aim was to examine disease-related and genetic correlates of the development of psychotic symptoms in a large population of patients with Parkinson's disease. We studied 500 patients with Parkinson's disease from the NeuroGenetics Research Consortium using logistic regression models. Predictors were demographic, clinical (motor/nonmotor features), and genetic, measured as continuous or dichotomous variables.

Postural instability/gait disturbance in Parkinson's disease has distinct subtypes: an exploratory analysis.

Objective: To test the hypothesis that postural instability with falling (PIF) and freezing of gait (FOG) are distinct subtypes of the postural instability/gait disturbance (PIGD) form of Parkinson's disease (PD).

Methods: 499 PD subjects from the NeuroGenetics Research Consortium were studied using logistic regression to examine, in a cross sectional analysis, predictors of FOG and PIF. Potential predictors were from four spheres; demographic, clinical motor, clinical non-motor and genetic.

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.

Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.

Genetic association between alpha-synuclein and idiopathic Parkinson's disease.

Point mutations and copy number variations in SNCA, the gene encoding alpha-synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis.

Exploring gene-environment interactions in Parkinson's disease.

The objective of this study was to explore combined effects of four candidate susceptibility genes and two exposures on Parkinson's disease (PD) risk; namely, alpha-synuclein (SNCA) promoter polymorphism REP1, microtubule-associated protein tau (MAPT) H1/H2 haplotypes, apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 polymorphism, ubiquitin carboxy-terminal esterase L1 (UCHL1) S18Y variant, cigarette smoking and caffeinated coffee consumption. 932 PD patients and 664 control subjects from the NeuroGenetics Research Consortium, with complete data on all six factors, were studied. Uniform protocols were used for diagnosis, recruitment, data collection and genotyping.

Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease.

UCHL1 has been proposed as a candidate gene for Parkinson's disease (PD). A meta-analysis of white and Asian subjects reported an inverse association between the non-synonymous UCHL1 S18Y polymorphism and PD risk. However, this finding was not replicated in a large case-control study and updated meta-analysis restricted to white subjects.

Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk.

Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium.

Association analysis of MAPT H1 haplotype and subhaplotypes in Parkinson's disease.

Objective: An inversion polymorphism of approximately 900 kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene defines two haplotype clades, H1 and H2. Several small case-control studies have observed a marginally significant excess of the H1/H1 diplotype among patients with Parkinson's disease (PD), and one reported refining the association to a region spanning exons 1 to 4 of MAPT. We sought to replicate these findings.

Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients.

Objective: Homozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous parkin mutations are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single "mutation" in a patient is related to disease or is coincidental, because the mutation frequency in control subjects is unknown. We present a comprehensive sequence analysis of parkin in control subjects.

Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study.

Background: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain.

Methods: Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs.

Validity and utility of a LRRK2 G2019S mutation test for the diagnosis of Parkinson's disease.

The G2019S mutation in the LRRK2 gene, the most common known cause of Parkinson's disease (PD), will soon be widely available as a molecular clinical test for PD. The objective of this study was to assess performance characteristics of G2019S as a clinical test for PD in the setting of typical movement disorder clinics in the United States. Subjects included 1,518 sequentially recruited PD patients from seven movement disorder clinics in the United States, and 1,733 unaffected subjects.

One step closer to fixing association studies: evidence for age- and gender-specific allele frequency variations and deviations from Hardy-Weinberg expectations in controls.

Association studies are the most powerful method available for identifying modest gene effects in complex disorders, but they often produce inconsistent results. With the rapidly growing SNP databases, haplotype maps and high throughput genotyping, the use of association studies is expected to increase; therefore, it is critical and timely that the problems with study design are identified and fixed. We questioned if unrecognized allele and genotype frequency variations in controls could be responsible for some of the inconsistent association findings.

Parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism.

Background: parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation.

Synergistic computational and experimental proteomics approaches for more accurate detection of active serine hydrolases in yeast.

An analysis of the structurally and catalytically diverse serine hydrolase protein family in the Saccharomyces cerevisiae proteome was undertaken using two independent but complementary, large-scale approaches. The first approach is based on computational analysis of serine hydrolase active site structures; the second utilizes the chemical reactivity of the serine hydrolase active site in complex mixtures. These proteomics approaches share the ability to fractionate the complex proteome into functional subsets.