Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: Characterization, ethnic distribution and evolutionary implications
| Autor: | Bert Gold, Karen M. Gehrs, Gregory S. Hageman, Joanna E. Merriam, David J. Kavanagh, John P. Atkinson, Julie Bergeron, Lincoln V. Johnson, Lisa S. Hancox, Seppo Meri, Michael Dean, Andrew J Taiber, Monte J. Radeke, Don H. Anderson, Rando Allikmets, Jana Zernant, Anna Richards |
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| Rok vydání: | 2017 |
| Předmět: |
Genotype
Blotting Western Locus (genetics) Biology Article Cohort Studies 03 medical and health sciences Macular Degeneration 0302 clinical medicine Gene Frequency medicine Humans Genotyping Allele frequency Polymorphism Single-Stranded Conformational 030304 developmental biology Genetics 0303 health sciences Haplotype Homozygote Racial Groups General Medicine Macular degeneration medicine.disease eye diseases 3. Good health Complement system Haplotypes Factor H Case-Control Studies Complement Factor H 030221 ophthalmology & optometry Alternative complement pathway sense organs Gene Deletion |
| Zdroj: | Annals of medicine. 38(8) |
| ISSN: | 1365-2060 |
| Popis: | Variants in the complement factor H gene (CFH) are associated with age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) lie within the regulators of complement activation (RCA) locus on chromosome 1q32. Aims and Methods. In this study, the structural and evolutionary relationships between these genes and AMD was refined using a combined genetic, molecular and immunohistochemical approach.We identify and characterize a large, common deletion that encompasses both the CFHR1 and CFHR3 genes. CFHR1, an abundant serum protein, is absent in subjects homozygous for the deletion. Genotyping analyses of AMD cases and controls from two cohorts demonstrates that deletion homozygotes comprise 1.1% of cases and 5.7% of the controls (chi-square=32.8; P= 1.6 E-09). CFHR1 and CFHR3 transcripts are abundant in liver, but undetectable in the ocular retinal pigmented epithelium/choroid complex. AMD-associated CFH/CFHR1/CFHR3 haplotypes are widespread in human populations.The absence of CFHR1 and/or CFHR3 may account for the protective effects conferred by some CFH haplotypes. Moreover, the high frequencies of the 402H allele and the delCFHR1/CFHR3 alleles in African populations suggest an ancient origin for these alleles. The considerable diversity accumulated at this locus may be due to selection, which is consistent with an important role for the CFHR genes in innate immunity. |
| Databáze: | OpenAIRE |
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