Semi-automated, reverse-hybridization detection of multiple mutations causing hereditary fructose intolerance
MOLECULAR AND CELLULAR PROBES
Authors: Kriegshauser, Gernot; Halsall, David; Rauscher, Bettina; Oberkanins, Christian
Abstract
Hereditary fructose intolerance (HFI) is a potentially fatal nutritional disease that is caused by mutations in the liver isoenzyme of fructoaldolase (aldolase 13). Our aim Was to evaluate a diagnostic assay capable of simultaneously analyzing three-point mutations and a small deletion in the aldolase B (ALDCIB) gene. The test under investigation is based on multiplex DNA amplification and hybridization to membrane strips presenting a parallel array of allele-specific oligonucleotide probes. We used the novel reverse-hybridization (RH) protocol to analyze 54 individuals previously genotyped by direct sequencing. RH genotyping for ALDOB mutations Delta 4E4, A149P, A174D, and N334K was in complete concordance with results obtained by DNA sequencing. The procedure is rapid (< 6h) and may be automated to a large extent. The RH assay tested in this study represents an accurate and robust screening tool to identify common ALDOB mutations. (c) 2007 Elsevier Ltd. All rights reserved.
Electronic medical records and genomics (eMERGE) network exploration in cataract: Several new potential susceptibility loci
MOLECULAR VISION
Authors: Ritchie, Marylyn D.; Verma, Shefali S.; Hall, Molly A.; Goodloe, Robert J.; Berg, Richard L.; Carrell, Dave S.; Carlson, Christopher S.; Chen, Lin; Crosslin, David R.; Denny, Joshua C.; Jarvik, Gail; Li, Rongling; Linneman, James G.; Pathak, Jyoti; Peissig, Peggy; Rasmussen, Luke V.; Ramirez, Andrea H.; Wang, Xiaoming; Wilke, Russell A.; Wolf, Wendy A.; Torstenson, Eric S.; Turner, Stephen D.; McCarty, Catherine A.
Abstract
Purpose: Cataract is the leading cause of blindness in the world, and in the United States accounts for approximately 60% of Medicare costs related to vision. The purpose of this study was to identify genetic markers for age-related cataract through a genome-wide association study (GWAS). Methods: In the electronic medical records and genomics (eMERGE) network, we ran an electronic phenotyping algorithm on individuals in each of five sites with electronic medical records linked to DNA biobanks. We performed a GWAS using 530,101 SNPs from the Illumina 660W-Quad in a total of 7,397 individuals (5,503 cases and 1,894 controls). We also performed an age-at-diagnosis case-only analysis. Results: We identified several statistically significant associations with age-related cataract (45 SNPs) as well as age at diagnosis (44 SNPs). The 45 SNPs associated with cataract at p<1x10(-5) are in several interesting genes, including ALDOB, MAP3K1, and MEF2C. All have potential biologic relationships with cataracts. Conclusions: This is the first genome-wide association study of age-related cataract, and several regions of interest have been identified. The eMERGE network has pioneered the exploration of genomic associations in biobanks linked to electronic health records, and this study is another example of the utility of such resources. Explorations of age-related cataract including validation and replication of the association results identified herein are needed in future studies.
COA
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