The University of Southampton
University of Southampton Institutional Repository

An analysis of allelic variation in the ABCA4 gene

Webster, Andrew R., Heon, Elise, Lotery, Andrew J., Vandenburgh, Kimberlie, Casavant, Thomas L., Oh, Kean T., Beck, Gretel, Fishman, Gerald A., Lam, Byron L., Levin, Alex, Heckenlively, John R., Jacobson, Samuel G., Weleber, Richard G., Sheffield, Val C. and Stone, Edwin M. (2001) An analysis of allelic variation in the ABCA4 gene Investigative Ophthalmology & Visual Science, 42, (6), pp. 1179-1189.

Record type: Article


PURPOSE. To assess the allelic variation of the ATP-binding transporter protein (ABCA4). METHODS. 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. RESULTS. 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. CONCLUSIONS. 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).

Full text not available from this repository.

More information

Published date: May 2001
Keywords: atp-binding cassette transporters, dna, linkage disequilibrium, acid, disease, alleles, genes, diagnosis, sequence analysis, adult, single-stranded conformational, research support, analysis, methods, genetic, variation (genetics), humans, codon, genetics, polymorphism, non-us government, comparative study, prevalence, time, protein, phs, macular degeneration, patients, amino acid substitution, us government
Organisations: Clinical Neurosciences


Local EPrints ID: 60405
ISSN: 0146-0404
PURE UUID: 707673cc-75e8-435d-b30a-68afd88624ac

Catalogue record

Date deposited: 02 Sep 2008
Last modified: 17 Jul 2017 14:23

Export record


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

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.