344 research outputs found
Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22
Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk
In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as well as gene set enrichment analyses (GSEA) and protein–protein interaction (PPI) network construction of top association hits genome-wide (p \u3c 0.01; n = 441 genes). The maximum likelihood estimate of heritability for epileptic seizure in the pedigreed baboon sample is 0.76 (SE = 0.77; p = 0.07). Among candidate genes for GGE, a significant association was detected for an intronic SNP in RBFOX1 (p = 5.92 × 10–6; adjusted p = 0.016). For protein-altering variants, no genome-wide significant results were observed for epilepsy status. However, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR = 0.0072) and collagen formation (FDR = 0.017), which was reflected in a major PPI network cluster. This preliminary study highlights the potential role of RBFOX1 in the epileptic baboon, a protein involved in transcriptomic regulation of multiple epilepsy candidate genes in humans and itself previously implicated in human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the genome exhibit a pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE and lay the foundation for follow-up research
Functional study of a genetic marker allele associated with resistance to Ascaris suum in pigs
Novel Associations of Nonstructural Loci with Paraoxonase Activity
The high-density-lipoprotein-(HDL-) associated esterase paraoxonase 1 (PON1) is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene, PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates—organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin—in 767 Mexican American individuals from San Antonio, Texas. Genetic influences on activity levels for each substrate were evaluated by association with approximately one million single nucleotide polymorphism (SNPs) while conditioning on PON1 genotypes. Significant associations were detected at five loci including regions on chromosomes 4 and 17 known to be associated with atherosclerosis and lipoprotein regulation and loci on chromosome 3 that regulate ubiquitous transcription factors. These loci explain 7.8% of variation in PON1 activity with lactone as a substrate, 5.6% with the arylester, and 3.0% with paraoxon. In light of the potential importance of PON1 in preventing cardiovascular disease/events, these novel loci merit further investigation
BR-squared: a practical solution to the winner’s curse in genome-wide scans
The detrimental effects of the winner’s curse, including overestimation of the genetic effects of associated variants and underestimation of sufficient sample sizes for replication studies are well-recognized in genome-wide association studies (GWAS). These effects can be expected to worsen as the field moves from GWAS into whole genome sequencing. To date, few studies have reported statistical adjustments to the naive estimates, due to the lack of suitable statistical methods and computational tools. We have developed an efficient genome-wide non-parametric method that explicitly accounts for the threshold, ranking, and allele frequency effects in whole genome scans. Here, we implement the method to provide bias-reduced estimates via bootstrap re-sampling (BR-squared) for association studies of both disease status and quantitative traits, and we report the results of applying BR-squared to GWAS of psoriasis and HbA1c. We observed over 50% reduction in the genetic effect size estimation for many associated SNPs. This translates into a greater than fourfold increase in sample size requirements for successful replication studies, which in part explains some of the apparent failures in replicating the original signals. Our analysis suggests that adjusting for the winner’s curse is critical for interpreting findings from whole genome scans and planning replication and meta-GWAS studies, as well as in attempts to translate findings into the clinical setting
Kernelization and Parameterized Algorithms for 3-Path Vertex Cover
A 3-path vertex cover in a graph is a vertex subset such that every path
of three vertices contains at least one vertex from . The parameterized
3-path vertex cover problem asks whether a graph has a 3-path vertex cover of
size at most . In this paper, we give a kernel of vertices and an
-time and polynomial-space algorithm for this problem, both new
results improve previous known bounds.Comment: in TAMC 2016, LNCS 9796, 201
Genome- and epigenome-wide association study of hypertriglyceridemic waist in Mexican American families
This file contains Supplementary Table 1. (XLSX 782 MB
Arbitrary Choice of Basic Variables in Density Functional Theory. II. Illustrative Applications
Our recent theory (Ref. 1) enables us to choose arbitrary quantities as the
basic variables of the density functional theory. In this paper we apply it to
several cases. In the case where the occupation matrix of localized orbitals is
chosen as a basic variable, we can obtain the single-particle equation which is
equivalent to that of the LDA+U method. The theory also leads to the
Hartree-Fock-Kohn-Sham equation by letting the exchange energy be a basic
variable. Furthermore, if the quantity associated with the density of states
near the Fermi level is chosen as a basic variable, the resulting
single-particle equation includes the additional potential which could mainly
modify the energy-band structures near the Fermi level.Comment: 27 page
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