Hudson Alpha Institute for Biotechnology

Huntsville, AL, United States

Hudson Alpha Institute for Biotechnology

Huntsville, AL, United States
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Aslibekyan A.,University of Alabama at Birmingham | Wiener H.W.,University of Alabama at Birmingham | Havel P.J.,University of California at Davis | Stanhope K.L.,University of California at Davis | And 5 more authors.
Journal of Nutrition | Year: 2014

A large body of evidence links a high dietary intake of n-3 (ω-3) polyunsaturated fatty acids (PUFAs) with improved cardiometabolic outcomes. Recent studies suggested that the biologic processes underlying the observed associations may involve epigenetic changes, specifically DNA methylation. To evaluate changes in methylation associated with n-3 PUFA intake, we conducted an epigenome-wide methylation association study of long-chain n-3 PUFA intake and tested associations between the diabetes-and cardiovascular disease-related traits. We assessed DNA methylation at;470,000 cytosine-phosphate-guanine (CpG) sites in a cross-sectional study of 185 Yup'ik Alaska Native individuals representing the top and bottom deciles of PUFA intake. Linear regression models were used to test for the associations of interest, adjusting for age, sex, and community group. We identified 27 differentially methylated CpG sites at biologically relevant regions that reached epigenome-wide significance (P < 1 × 10-27). Specifically, regions on chromosomes 3 (helicase-like transcription factor), 10 (actin a 2 smooth muscle/Fas cell surface death receptor), and 16 (protease serine 36/C16 open reading frame 67) each harbored 2 significant correlates of n-3 PUFA intake. In conclusion, we present promising evidence of association between several biologically relevant epigenetic markers and long-term intake of marine-derived n-3 PUFAs. © 2014 American Society for Nutrition.


Zhi D.,University of Alabama at Birmingham | Aslibekyan S.,University of Alabama at Birmingham | Irvin M.R.,University of Alabama at Birmingham | Claas S.A.,University of Alabama at Birmingham | And 4 more authors.
Epigenetics | Year: 2013

DNA methylation is an important molecular-level phenotype that links genotypes and complex disease traits. Previous studies have found local correlation between genetic variants and DNA methylation levels (cis-meQTLs). However, general mechanisms underlying cis-meQTLs are unclear. We conducted a cis-meQTL analysis of the Genetics of Lipid Lowering Drugs and Diet Network data (n = 593). We found that over 80% of genetic variants at CpG sites (meSNPs) are meQTL loci (P-value < 10-9), and meSNPs account for over two thirds of the strongest meQTL signals (P-value < 10-200). Beyond direct effects on the methylation of the meSNP site, the CpG-disrupting allele of meSNPs were associated with lowered methylation of CpG sites located within 45 bp. The effect of meSNPs extends to as far as 10 kb and can contribute to the observed meQTL signals in the surrounding region, likely through correlated methylation patterns and linkage disequilibrium. Therefore, meSNPs are behind a large portion of observed meQTL signals and play a crucial role in the biological process linking genetic variation to epigenetic changes. © 2013 Landes Bioscience.


Hidalgo B.,University of Alabama at Birmingham | Irvin M.R.,University of Alabama at Birmingham | Sha J.,University of Alabama at Birmingham | Zhi D.,University of Alabama at Birmingham | And 6 more authors.
Diabetes | Year: 2014

Known genetic susceptibility loci for type 2 diabetes (T2D) explain only a small proportion of heritable T2D risk. We hypothesize that DNA methylation patterns may contribute to variation in diabetes-related risk factors, and this epigenetic variation across the genome can contribute to the missing heritability in T2D and related metabolic traits. We conducted an epigenome-wide association study for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) among 837 nondiabetic participants in the Genetics of Lipid Lowering Drugs and Diet Network study, divided into discovery (N = 544) and replication (N = 293) stages. Cytosine guanine dinucleotide (CpG) methylation at ;470,000 CpG sites was assayed in CD4+ T cells using the Illumina Infinium HumanMethylation 450 Beadchip. We fit a mixed model with the methylation status of each CpG as the dependent variable, adjusting for age, sex, study site, and T-cell purity as fixed-effects and family structure as a random-effect. A Bonferroni corrected P value of 1.1 3 1027 was considered significant in the discovery stage. Significant associations were tested in the replication stage using identical models. Methylation of a CpG site in ABCG1 on chromosome 21 was significantly associated with insulin (P = 1.83 3 1027) and HOMA-IR (P = 1.60 3 1029). Another site in the same gene was significant for HOMA-IR and of borderline significance for insulin (P = 1.29 3 1027 and P = 3.36 3 1026, respectively). Associations with the top two signals replicated for insulin and HOMA-IR (P = 5.75 3 1023 and P = 3.35 3 1022, respectively). Our findings suggest that methylation of a CpG site within ABCG1 is associated with fasting insulin and merits further evaluation as a novel disease risk marker. © 2014 by the American Diabetes Association.


Turner C.A.,University of Michigan | Thompson R.C.,University of Michigan | Bunney W.E.,University of California at Irvine | Schatzberg A.F.,Stanford University | And 4 more authors.
Frontiers in Human Neuroscience | Year: 2014

Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus (CP), the region that produces cerebrospinal fluid (CSF), in individuals with major depressive disorder (MDD). Genes that are expressed in the CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the CP at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled, and hybridized the cRNA to Illumina Bead Chips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using Bead Studio software, we identified 169 transcripts differentially expressed (p < 0.05) between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ) pathway. Quantitative real-time PCR (qRT-PCR) confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the CP in MDD subjects that may lead to a disrupted blood-CSF-brain barrier. © 014 Turner, Thompson, Bunney, Schatzberg, Barchas, Myers, Akil and Watson.


Cooper G.M.,Hudson Alpha Institute for Biotechnology | Mefford H.C.,University of Washington
Methods in Molecular Biology | Year: 2011

Genetic diversity among human genomes comes in many forms, including single nucleotide polymorphisms (SNPs) and small insertions and deletions on the order of one to several basepairs. More recently, large, >1 kb copy number changes have been identified as an important source of normal genomic variation as well as disease-causing variation. The ability to perform genome-wide discovery of large copy number variants (CNVs) has been facilitated by advances in two technologies - array comparative genomic hybridization and SNP genotyping platforms. Here, we discuss the general principles and strategies underlying CNV detection with SNP genotyping platforms, which are widely used and capable of providing both SNP and CNV genotyping information. © 2011 Springer Science+Business Media, LLC.


Chiu I.M.,Harvard University | Morimoto E.T.,Columbia University | Goodarzi H.,Rockefeller University | Liao J.T.,Columbia University | And 8 more authors.
Cell Reports | Year: 2013

Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury, and inflammation. Here, we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation invivo. Analysis of resting microglia identified 29 genes that distinguish microglia from other CNS cells and peripheral macrophages/monocytes. We then analyzed molecular changes in microglia during neurodegenerative disease activation using the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS). We found that SOD1G93A microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors, including Alzheimer@s disease genes, are concurrently upregulated. Mutant microglia differed from SOD1WT, lipopolysaccharide-activated microglia, and M1/M2 macrophages, defining an ALS-specific phenotype. Concurrent messenger RNA/fluorescence-activated cell sorting analysis revealed posttranscriptional regulation of microglia surface receptors and Tcell-associated changes in the transcriptome. These results provide insights into microglia biology and establish a resource for future studies of neuroinflammation


Kobayashi Y.,Stanford University | Absher D.M.,Hudson Alpha Institute for Biotechnology | Gulzar Z.G.,Stanford University | Young S.R.,Stanford University | And 5 more authors.
Genome Research | Year: 2011

Candidate gene-based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer. However, DNA methylation profiles have not been compared on a large scale between prostate tumor and normal prostate, and the mechanisms behind these alterations are unknown. In this study, we quantitatively profiled 95 primary prostate tumors and 86 benign adjacent prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform. A 2-class Significance Analysis of this data set revealed 5912 CpG sites with increased DNA methylation and 2151 CpG sites with decreased DNA methylation in tumors (FDR < 0.8%). Prediction Analysis of this data set identified 87 CpGs that are the most predictive diagnostic methylation biomarkers of prostate cancer. By integrating available clinical follow-up data, we also identified 69 prognostic DNA methylation alterations that correlate with biochemical recurrence of the tumor. To identify the mechanisms responsible for these genome-wide DNA methylation alterations, we measured the gene expression levels of several DNA methyltransferases (DNMTs) and their interacting proteins by TaqMan qPCR and observed increased expression of DNMT3A2, DNMT3B, and EZH2 in tumors. Subsequent transient transfection assays in cultured primary prostate cells revealed that DNMT3B1 and DNMT3B2 overexpression resulted in increased methylation of a substantial subset of CpG sites that showed tumor-specific increased methylation. © 2011 by Cold Spring Harbor Laboratory Press.


Trademark
Hudson Alpha Institute For Biotechnology | Date: 2012-03-27

Printed instructional educational and teaching materials in the field of biology; educational publications, namely teaching manuals and manipulative games; teaching aids used for teaching biology.


Trademark
Hudson Alpha Institute For Biotechnology | Date: 2012-01-24

Educational teaching aids, namely, educational toy kits comprising educational toys and laboratory reagents used for teaching biology sold as a unit.


Trademark
Hudson Alpha Institute For Biotechnology | Date: 2012-04-05

boxes used to ship educational and teaching materials in the field of biology.

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