Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease

Kucukkilic, E, Brookes, K ORCID: https://orcid.org/0000-0003-2427-2513, Barber, I, Guetta-Baranes, T, Morgan, K and Hollox, EJ, 2018. Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease. Human Genetics, 137 (4), pp. 305-314. ISSN 0340-6717

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Abstract

Single nucleotide variants (SNVs) within and surrounding the complement receptor 1 (CR1) gene show some of the strongest genome-wide association signals with late-onset Alzheimer’s disease. Some studies have suggested that this association signal is due to a duplication allele (CR1-B) of a low copy repeat (LCR) within the CR1 gene, which increases the number of complement C3b/C4b-binding sites in the mature receptor. In this study, we develop a triplex paralogue ratio test assay for CR1 LCR copy number allowing large numbers of samples to be typed with a limited amount of DNA. We also develop a CR1-B allele-specific PCR based on the junction generated by an historical non-allelic homologous recombination event between CR1 LCRs. We use these methods to genotype CR1 and measure CR1-B allele frequency in both late-onset and early-onset cases and unaffected controls from the United Kingdom. Our data support an association of late-onset Alzheimer’s disease with the CR1-B allele, and confirm that this allele occurs most frequently on the risk haplotype defined by SNV alleles. Furthermore, regression models incorporating CR1-B genotype provide a better fit to our data compared to incorporating the SNV-defined risk haplotype, supporting the CR1-B allele as the variant underlying the increased risk of late-onset Alzheimer’s disease.

Item Type:	Journal article
Publication Title:	Human Genetics
Creators:	Kucukkilic, E., Brookes, K., Barber, I., Guetta-Baranes, T., Morgan, K. and Hollox, E.J.
Publisher:	Springer
Date:	April 2018
Volume:	137
Number:	4
ISSN:	0340-6717
Identifiers:	Number Type 10.1007/s00439-018-1883-2 DOI
Rights:	© the author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Record created by:	Jonathan Gallacher
Date Added:	15 May 2019 09:15
Last Modified:	15 May 2019 09:15
URI:	https://irep.ntu.ac.uk/id/eprint/36546

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