Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English English |
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Springer
2018
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| Online Access: | https://eprints.nottingham.ac.uk/50597/ |
| _version_ | 1848798292497924096 |
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| author | Kucukkilic, Ezgi Brookes, Keeley Barber, Imelda Guetta-Baranes, Tamar Morgan, Kevin Hollox, Edward |
| author_facet | Kucukkilic, Ezgi Brookes, Keeley Barber, Imelda Guetta-Baranes, Tamar Morgan, Kevin Hollox, Edward |
| author_sort | Kucukkilic, Ezgi |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 (PRT) 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 bitter fit to our data compared to incorporating the SNP-defined risk haplotype, supporting the CR1-B allele as the variant underlying the increased risk of late-onset Alzheimer’s disease. |
| first_indexed | 2025-11-14T20:17:27Z |
| format | Article |
| id | nottingham-50597 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-14T20:17:27Z |
| publishDate | 2018 |
| publisher | Springer |
| recordtype | eprints |
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| spelling | nottingham-505972018-06-12T05:55:00Z https://eprints.nottingham.ac.uk/50597/ Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease Kucukkilic, Ezgi Brookes, Keeley Barber, Imelda Guetta-Baranes, Tamar Morgan, Kevin Hollox, Edward 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 (PRT) 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 bitter fit to our data compared to incorporating the SNP-defined risk haplotype, supporting the CR1-B allele as the variant underlying the increased risk of late-onset Alzheimer’s disease. Springer 2018-04-19 Article PeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/50597/8/10.1007%252Fs00439-018-1883-2.pdf application/pdf en cc_by https://eprints.nottingham.ac.uk/50597/1/284711.full.pdf Kucukkilic, Ezgi, Brookes, Keeley, Barber, Imelda, Guetta-Baranes, Tamar, Morgan, Kevin and Hollox, Edward (2018) Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease. Human Genetics . pp. 1-10. ISSN 1432-1203 https://link.springer.com/article/10.1007%2Fs00439-018-1883-2 doi:10.1007/s00439-018-1883-2 doi:10.1007/s00439-018-1883-2 |
| spellingShingle | Kucukkilic, Ezgi Brookes, Keeley Barber, Imelda Guetta-Baranes, Tamar Morgan, Kevin Hollox, Edward Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease |
| title | Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease |
| title_full | Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease |
| title_fullStr | Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease |
| title_full_unstemmed | Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease |
| title_short | Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease |
| title_sort | complement receptor 1 gene (cr1) intragenic duplication and risk of alzheimer’s disease |
| url | https://eprints.nottingham.ac.uk/50597/ https://eprints.nottingham.ac.uk/50597/ https://eprints.nottingham.ac.uk/50597/ |