@article{c17c0217057e4e32b693719620dc71b0,
title = "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",
abstract = "Background. 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. Results. 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. Conclusion. 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.",
keywords = "Age-related macular degeneration, Alternative pathway, Complement, Deletion, Evolution, Factor H, Factor H-related, Haplotype, Vision",
author = "Hageman, \{Gregory S.\} and Hancox, \{Lisa S.\} and Taiber, \{Andrew J.\} and Gehrs, \{Karen M.\} and Anderson, \{Don H.\} and Johnson, \{Lincoln V.\} and Radeke, \{Monte J.\} and David Kavanagh and Anna Richards and John Atkinson and Seppo Meri and Julie Bergeron and Jana Zernant and Joanna Merriam and Bert Gold and Rando Allikmets and Michael Dean and Jill Hageman and Jamal Hoballah and Heather Stockman and Ilkka Immonen and Matti Laine and Hanna Jarva and Irma J{\"a}rvel{\"a} and Sanna Seitsonen and Gaetano Barile and Stanley Chang and Merriam, \{John C.\} and Smith, \{R. Theodore\} and Yannuzzi, \{Lawrence A.\}",
note = "Funding Information: This project has been supported by NIH R01 EY11515 (GH), R24 EY017404 (GH, RA, LJ, DA), R01 EY13435 (RA), R01 EY11527 (LJ) and R01 EY11521 (DA), DHHS contract \#NO1-CO-12400 (MD), the National Cancer Institute (MD), the Inframural Research Program of NIH (MD), International Retina Research Foundation (GH), Foundation Fighting Blindness (RA), Ruth and Milton Steinbach Fund (GH, RA), New York Community Trust (RTS), Wallach Foundation (RA, GRB), Elyachar Foundation (RA, GRB), Kaplen Foundation (RA, GRB), Widgeon Point Charitable Foundation (RA, JEM), Macula Vision Research Foundation (RA) and unrestricted grants to the University of Iowa and Columbia University from Research to Prevent Blindness, Inc. GSH holds honorary professorships in the School of Medicine, Queen{\textquoteright}s University, Belfast and the Shandong Eye Institute, Qingdao, China.",
year = "2006",
month = dec,
doi = "10.1080/07853890601097030",
language = "English",
volume = "38",
pages = "592--604",
journal = "Annals of Medicine",
issn = "0785-3890",
publisher = "Taylor and Francis Ltd.",
number = "8",
}