An analysis of allelic variation in the ABCA4 gene

Andrew R Webster; Elise Heon; Andrew J Lotery; Kimberlie Vandenburgh; Thomas L Casavant; Kean T Oh; Gretel Beck; Gerald A Fishman; Byron L Lam; Alex Levin; John R Heckenlively; Samuel G Jacobson; Richard G Weleber; Val C Sheffield; Edwin M Stone

An analysis of allelic variation in the ABCA4 gene

Journal article

Peer reviewed

An analysis of allelic variation in the ABCA4 gene

Andrew R Webster, Elise Heon, Andrew J Lotery, Kimberlie Vandenburgh, Thomas L Casavant, Kean T Oh, Gretel Beck, Gerald A Fishman, Byron L Lam, Alex Levin, …

Investigative ophthalmology & visual science, Vol.42(6), pp.1179-1189

05/2001

PMID: 11328725

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Abstract

To assess the allelic variation of the ATP-binding transporter protein (ABCA4). A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to systematically screen this gene for sequence variations in 374 unrelated probands with a clinical diagnosis of Stargardt disease, 182 patients with age-related macular degeneration (AMD), and 96 normal subjects. There was no significant difference in the proportion of any single variant or class of variant between the control and AMD groups. In contrast, truncating variants, amino acid substitutions, synonymous codon changes, and intronic variants were significantly enriched in patients with Stargardt disease when compared with their presence in subjects without Stargardt disease (Kruskal-Wallis P < 0.0001 for each variant group). Overall, there were 2480 instances of 213 different variants in the ABCA4 gene, including 589 instances of 97 amino acid substitutions, and 45 instances of 33 truncating variants. Of the 97 amino acid substitutions, 11 occurred at a frequency that made them unlikely to be high-penetrance recessive disease-causing variants (HPRDCV). After accounting for variants in cis, one or more changes that were compatible with HPRDCV were found on 35% of all Stargardt-associated alleles overall. The nucleotide diversity of the ABCA4 coding region, a collective measure of the number and prevalence of polymorphic sites in a region of DNA, was found to be 1.28, a value that is 9 to 400 times greater than that of two other macular disease genes that were examined in a similar fashion (VMD2 and EFEMP1).

Genetic Variation

Polymorphism, Single-Stranded Conformational

ATP-Binding Cassette Transporters - genetics

Macular Degeneration - genetics

Humans

Alleles

Adult

Sequence Analysis, DNA

Linkage Disequilibrium

Polymorphism, Genetic

Details

Title: Subtitle: An analysis of allelic variation in the ABCA4 gene
Creators: Andrew R Webster - Department of Ophthalmology, The University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
Elise Heon
Andrew J Lotery
Kimberlie Vandenburgh
Thomas L Casavant
Kean T Oh
Gretel Beck
Gerald A Fishman
Byron L Lam
Alex Levin
John R Heckenlively
Samuel G Jacobson
Richard G Weleber
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.42(6), pp.1179-1189
PMID: 11328725
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: EY10539 / NEI NIH HHS
Language: English
Date published: 05/2001
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980005902771

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