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Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B
Author(s) -
Breunis Willemijn B.,
van Mirre Edwin,
Geissler Judy,
Laddach Nadja,
Wolbink Gertjan,
van der Schoot Ellen,
de Haas Masja,
de Boer Martin,
Roos Dirk,
Kuijpers Taco W.
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20997
Subject(s) - copy number variation , biology , single nucleotide polymorphism , locus (genetics) , genetics , multiplex ligation dependent probe amplification , gene , multiplex , microbiology and biotechnology , genotype , exon , genome
Abstract Human Fcã receptors (FcãRs) are glycoproteins that bind the Fc region of IgG. The genes encoding the low‐affinity FcãRs 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 FcãRs 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 FcãRIIIa 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 FcãRIIIa expression and function on NK cells. Only FCGR3A , FCGR2C and FCGR3B show CNV, in contrast to FCGR2A and FCGR2B . © 2009 Wiley‐Liss, Inc.