| Autor: |
Kucukkilic, Ezgi, Brookes, Keeley, Barber, Imelda, Guetta-Baranes, Tamar, ARUK Consortium, Morgan, Kevin, Hollox, Edward J. |
| Předmět: |
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| Zdroj: |
Human Genetics; Apr2018, Vol. 137 Issue 4, p305-314, 10p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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