Welcome to the Vanderbilt Vision Research Center Microarray Core webpage, spotlighting the latest information regarding genomic technologies as they relate to VVRC interests. Members of the VVRC are urged to contact the VMSR to find out how microarray, genotyping, and RNAi technologies may enhance their research. Three VMSR bioinformaticists are available to help members design and plan experiments, obtain high-quality data, and prepare the data for publication. New platforms, products, and analysis techniques allow exploration of genomics in ways never before possible.
Featured research
Complement factor H polymorphism in age-related macular degeneration.
Science. 2005 Apr 15; 308(5720):385-9 [Epub 2005 Mar 10]
This manuscript used whole-genome mapping technology to uncover the role of a single nucleotide polymorphism (SNP) in age-related macular degeneration (AMD), a major cause of blindness in the elderly. The Affymetrix GeneChip Mapping 100K Set of microarrays was used to perform a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. This mapping assay consisted of two chips (XbaI and HindIII) with approximately 50,000 SNPs each that were run using DNA from every individual in the study. Over 116K SNPs were genotyped and tested for allelic association with disease status. On initial analysis, two SNPs (rs380390 and rs10272438) were found to be strongly associated with disease status. SNP rs380390 was successfully genotyped in all individuals. No genotype was determined for SNP rs10272438 in 21 individuals, and upon further analysis, it appeared to be excessively out of Hardy-Weinberg equilibrium, indicating possible genotyping errors. Missing genotypes of rs10272438 were determined by resequencing and after inclusion of this data, the association with AMD was no longer significant. However, SNP rs380390, an intronic and common variant in the complement factor H gene (CFH), was found to be strongly associated with AMD. Since this manuscript was published, other groups have continued to profile the role of CFH in AMD in different populations.
- Arora A, Simpson DA
Individual mRNA expression profiles reveal the effects of specific microRNAs.
Genome Biol. 2008; 9(5):R82 [Epub 2008 May 16] - Maia-Lopes S, Silva ED, Silva MF, Reis A, Faria P, Castelo-Branco M
Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives.
Invest Ophthalmol Vis Sci. 2008 Mar; 49(3):1191-9 - Fung ES, Ng MK
On sparse Fisher discriminant method for microarray data analysis.
Bioinformation. 2007 Dec 30; 2(5):230-4 - Mantel I, Ramchand KV, Holder GE, Ohbayashi M, Morohoshi K, Patel N, Toda M, Fitzke FW, Bird AC, Ono SJ
Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.
Exp Mol Pathol. 2008 Apr; 84(2):90-101 [Epub 2007 Nov 9] - Rosenberg T, Klie F, Garred P, Schwartz M
N965S is a common ABCA4 variant in Stargardt-related retinopathies in the Danish population.
Mol Vis. 2007 Oct 17; 13:1962-9
- Burke W, Kuszler P, Starks H, Holland S, Press N
Translational genomics: seeking a shared vision of benefit.
Am J Bioeth. 2008 Mar; 8(3):54-6; discussion W1-3 - Leist M, Hartung T, Nicotera P
The dawning of a new age of toxicology.
ALTEX. 2008; 25(2):103-14 - Yokoyama S
Evolution of Dim-Light and Color Vision Pigments.
Annu Rev Genomics Hum Genet. 2008 Jun 10; [Epub ahead of print] - Shabo A
Integrating genomics into clinical practice: Standards and regulatory challenges.
Curr Opin Mol Ther. 2008 Jun; 10(3):267-72
- Leachman SA, Hickerson RP, Hull PR, Smith FJ, Milstone LM, Lane EB, Bale SJ, Roop DR, McLean WH, Kaspar RL
Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita.
J Dermatol Sci. 2008 May 19; [Epub ahead of print] - Paskowitz DM, Greenberg KP, Yasumura D, Grimm D, Yang H, Duncan JL, Kay MA, Lavail MM, Flannery JG, Vollrath D
Rapid and stable knockdown of an endogenous gene in retinal pigment epithelium.
Hum Gene Ther. 2007 Oct; 18(10):871-80 - Forooghian F, Das B
Anti-angiogenic effects of ribonucleic acid interference targeting vascular endothelial growth factor and hypoxia-inducible factor-1alpha.
Am J Ophthalmol. 2007 Nov; 144(5):761-8 [Epub 2007 Sep 17]
News and Notes
- Previously analyzed data could benefit from a second look using new analysis techniques and software, which can uncover expression patterns, provide pathway analysis, or drug discovery information.
- Agilent arrays are now offered for CGH and gene expression analysis.
- Interested in miRNA detection? Exiqon miRCURY™ LNA microRNA Arrays offer high-quality miRNA data from total RNA - no fractionation required!
- Tiling arrays are a discovery tool for studying gene regulation, including mapping sites of protein/DNA interaction in ChIP experiments, discovering new RNA transcripts, and understanding DNA methylation or acetylation.
- VMSR functional genomics capabilities include RNAi and full-length cDNA libraries, with clones available to Vanderbilt researchers at a fraction of the cost of commercial websites. Synthetic RNAi libraries with specific focuses are also available, including Human Druggable Genome, Protein Kinase, Phosphatases, and GPCR screening libraries.
- The newest DNA Mapping arrays probe almost 1 million SNPs and an additional 1 million copy number analysis probes. High-throughput handling in the VMSR has yielded decreased costs, making genotyping affordable to any budget. Copy number analysis can be done on as little as one tumor or diseased sample, when compared to publicly available normal controls.
Selected papers of interest
Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.
Genome Biol. 2007; 8(11):R248
Loscher et al utilized two different microRNA microarrays (Exiqon and Ambion) to construct a miRNA profile of retinitis pigmentosa in mice.
Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease.
Mol Vis. 2007 Aug 31; 13:1568-72
Using a custom Affymetrix resequencing microarray, Yzer et al identified a shared ABCA4 mutation in a family with high incidence of two related retinal dystrophies. In addition, they identified a novel mutation shared by the patients with with arCRD, and a separate novel mutation in the patient with STGD1.
