Evidence for gene recombination in FCGR3 gene variants

Authors: Blum, K. S.; Tong, Y.¹; Siebert, R.²; Marget, M.³; Humpe, A.⁴; Neppert, J.⁵; Flesch, B. K.⁵

Source: Vox Sanguinis, Volume 97, Number 1, July 2009 , pp. 69-76(8)

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Abstract:

Background and Objectives

The genes encoding the Fcγ receptors (FcγR) IIIa and IIIb (FCGR3A and FCGR3B) are clustered on chromosome 1 band q23-24 and exhibit allelic polymorphism. We investigated the molecular basis of additional new FCGR3 genomic variation. Materials and Methods

A segment shared by FCGR3A and FCGR3B containing the polymorphic nucleotide positions 141, 147, 227, 266, and 277 in exon 3 was cloned and sequenced from genomic DNA of 30 donors and 3 bacterial artificial chromosome (BAC) clones. A mixture consisting of isolated FCGR3B*2- and FCGR3A- plasmids was cloned and sequenced as well. Additionally, nucleotide databases were screened for clones with variant FCGR3 sequences. Results

A total of 12 FCGR3 variants defined by the polymorphic positions were detected in whole blood genomic DNA from 23 of 24 FCGR3B*2 and/or FCGR3B*3 positive donors, the DNA from two of three BAC clones and in the DNA mixture of isolated FCGR3B*2- and FCGR3A- plasmids. Conclusion

Nucleotide exchanges of the variants were non-random and resulted from two alternative nucleotides present in one of the polymorphic position of the basic FCGR3 forms. Polymerase chain reaction (PCR) artefacts cannot be excluded as origin of new variants, but there is strong evidence that at least two variants are the result of a somatic recombination.

Keywords: FCGR3B; Fcγ receptor; gene variation; segregation; somatic recombination

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1423-0410.2009.01178.x

Affiliations: 1: Department of Haematolgoy, 1st Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China 2: Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany 3: Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany 4: Stem Cell Laboratory of the Second Department of the Medical University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany 5: Institute of Transfusion Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

Publication date: 2009-07-01

Evidence for gene recombination in FCGR3 gene variants

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