title: Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B.
abstract: Human Fcgamma receptors (FcgammaRs) are glycoproteins that bind the Fc region of IgG. The genes encoding the low-affinity FcgammaRs are located on chromosome 1q23-24. Beside single nucleotide polymorphisms (SNPs), gene copy number variation (CNV) is now being recognized as an important indicator for inter-individual differences. Recent studies on identifying CNV in the human genome suggest large areas at chromosome 1q23-24 to be involved, and CNV in this region has been associated with manifestations of systemic autoimmune disease. To study both SNPs and CNV of the low-affinity FcgammaRs in one assay, we have developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. A novel CNV for FCGR3A was observed. Similar to FCGR3B and FCGR2C, a gene-dosage effect of FCGR3A was found, that seemed to correlate nicely with the FcgammaRIIIa expression on NK cells. Next, we delineated the approximate boundaries of CNV at the FCGR locus. Variation in co-segregation of neighboring FCGR genes was limited to four variants, with patterns of Mendelian inheritance. No CNV of the FCGR2A and FCGR2B genes was observed in over 600 individuals. In conclusion, we report a novel CNV of the FCGR3A gene that correlates with FcgammaRIIIa expression and function on NK cells. Only FCGR3A, FCGR2C and FCGR3B show CNV, in contrast to FCGR2A and FCGR2B.
authors.affiliation: Department of Pediatric Hematology, Immunology & Infectious Disease at Emma Children's Hospital, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: Willemijn B
authors.initials: WB
authors.lastname: Breunis
authors.forename: Edwin
authors.initials: E
authors.lastname: van Mirre
authors.forename: Judy
authors.initials: J
authors.lastname: Geissler
authors.forename: Nadja
authors.initials: N
authors.lastname: Laddach
authors.forename: Gertjan
authors.initials: G
authors.lastname: Wolbink
authors.forename: Ellen
authors.initials: E
authors.lastname: van der Schoot
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.forename: Martin
authors.initials: M
authors.lastname: de Boer
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D018628:Gene Dosage; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: C445323:FCGR2A protein, human; C499173:FCGR2B protein, human; C496124:FCGR3A protein, human; C428200:FCGR3B protein, human; C080572:Fc gamma receptor IIC; D058851:GPI-Linked Proteins; D017452:Receptors, IgG