Posts Tagged: genomics

From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease

From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease

Sylvia T. Nurnberg*, Hanrui Zhang*, Nicholas J. Hand, Robert C. Bauer, Danish Saleheen, Muredach P. Reilly, Daniel J. Rader

Mechanism by which noncoding risk single nucleotide polymorphisms (SNP) can affect phenotype. Top, Multiple SNPs associated with disease are located in the intergenic region proximal to genes A, B, and C. One of the SNPs with genome-wide significance is situated within a cis-regulatory element (orange tag). The lowest P value SNP (lead SNP, flag tag) lies outside the regulatory element. Bottom, Through bending of the DNA molecule, the regulatory element gets into physical contact with the promoter of its target gene, in this case gene C, which is not the gene in closest proximity, leading to regulation of its expression (activation or upregulation in case of an enhancer element). The SNP located within the regulatory element (functional SNP, orange tag) can now affect transcription by, for instance, altering transcription factor (TF)–binding affinity based on genotype via disruption of a TF-binding motif. [Powerpoint File]

From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease

From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease

Sylvia T. Nurnberg*, Hanrui Zhang*, Nicholas J. Hand, Robert C. Bauer, Danish Saleheen, Muredach P. Reilly, Daniel J. Rader

Coronary heart disease (CHD) genome-wide association studies (GWAS) risk genes are active in selective cell types involved in atherosclerosis. Coronary heart disease follow-up studies have demonstrated roles for LIPA, SORT1, and TRIB1 as plasma lipid regulators in the liver, as well as in macrophages biology. Within the vessel wall, TCF21 is upregulated in dedifferentiated smooth muscle cells which migrate to the forming fibrous cap. Adamts7 is also a regulator of smooth muscle migration but also a role in endothelial cells has been suggested. [Powerpoint File]

Acute Coronary Syndromes Compendium: Genetics of Coronary Artery Disease

Acute Coronary Syndromes Compendium: Genetics of Coronary Artery Disease

Robert Roberts

Low-density lipoproteinn (LDL) and its cholesterol (LDL-C) are synthesized in the liver, and by binding to the LDL receptor (LDL-R), LDL-C is removed from the circulation. Statin X indicates that the class of drugs known as statins inhibits the synthesis of LDL-C. PCSK9 normally delays removal of LDL-C from the circulation. Inhibition of PCSK9 leads to faster removal of LDL-C and lower levels of circulating LDL-C. Reprinted from Roberts99 with permission of the publisher. Copyright ©2008, Elsevier. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. [Powerpoint FIle]

Overview of High Throughput Sequencing Technologies to Elucidate Molecular Pathways in Cardiovascular Diseases

Overview of High Throughput Sequencing Technologies to Elucidate Molecular Pathways in Cardiovascular Diseases

Jared M. Churko, Gary L. Mantalas, Michael P. Snyder, Joseph C. Wu

Nanopore technology. Third-generation sequencing is expected to measure the change in ion flow (current) within a membrane as small molecules are passed through a small pore inside the membrane. Different current profiles will, therefore, indicate which nucleotide passed through and in which order. [Powerpoint File]

Drosophila, Genetic Screens, and Cardiac Function

Drosophila, Genetic Screens, and Cardiac Function

Matthew J. Wolf, Howard A. Rockman

The embryonic and adult Drosophila circulatory system. A, The developing embryonic circulatory system arises from cardial precursor cells that migrate to form the dorsal vessel at Stage 16. Stages 12, 13, and 17 are shown. The figure is adapted from Fly Embryo RNAi Project (http://flyembryo.nhlbi.nih.gov). B, The adult fly circulatory system consists of an open system with the main conical chamber, heart, located along the dorsal aspect of the A1 abdominal segment. Suspensory muscles including the alary and ventral longitudinal muscle, also referred to as the dorsal diaphragm. Pericardial cells are closely juxtaposed along the length of the abdominal portion of the circulatory system. The figure is adapted from that of Miller.72 A 1-mm scale bar is shown for comparison. [Powerpoint File]