Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/41939
Title: Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease
Authors: Kucukkilic, Ezgi
Brookes, K.
Barber, I.
Guetta-Baranes, T.
ARUK Consortium
Morgan, K.
Hollox, Edward J.
First Published: 19-Apr-2018
Publisher: Springer Verlag
Citation: Human Genetics, 2018
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.
DOI Link: 10.1007/s00439-018-1883-2
ISSN: 0340-1203
eISSN: 1432-1203
Links: https://link.springer.com/article/10.1007%2Fs00439-018-1883-2
http://hdl.handle.net/2381/41939
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Genetics

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