TY - JOUR
T1 - Structural variation of the mouse natural killer gene complex
AU - Higuchi, D. A.
AU - Cahan, P.
AU - Gao, J.
AU - Ferris, S. T.
AU - Poursine-Laurent, J.
AU - Graubert, T. A.
AU - Yokoyama, W. M.
N1 - Funding Information:
The authors thank Megan Cooper and Beatrice Plougastel for careful reading of the manuscript. Funding. Work in the Yokoyama laboratory is supported by grants from the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute. The Graubert laboratory is supported by the National Cancer Institute (P01 CA101937).
PY - 2010/12
Y1 - 2010/12
N2 - The natural killer gene complex (NKC) on chromosome 6 contains clusters of genes that encode both activation and inhibitory receptors expressed on mouse natural killer (NK) cells. NKC genes, particularly belonging to the Nkrp1 and Ly49 gene families, display haplotype differences between different mouse strains and allelic polymorphisms of individual genes, as previously revealed by conventional analysis in a small number of inbred mouse strains. Herein we used array-based comparative genomic hybridization (aCGH) to efficiently compare the NKC in 21 mouse strains to the reference C57BL/6 strain. By using unsupervised clustering methods, we could sort these variations into the same groups as determined by previous RFLP analyses of Nkrp1 and Ly49 genes. Prospective analyses of aCGH and RFLP data validated these relationships. Moreover, aCGH data predicted monoclonal antibody reactivity with an allospecific determinant on molecules expressed by NK cells. Taken together, these data demonstrate the structural variation in the NKC between mouse strains as well as the usefulness of aCGH in analysis of complex, polymorphic gene clusters.
AB - The natural killer gene complex (NKC) on chromosome 6 contains clusters of genes that encode both activation and inhibitory receptors expressed on mouse natural killer (NK) cells. NKC genes, particularly belonging to the Nkrp1 and Ly49 gene families, display haplotype differences between different mouse strains and allelic polymorphisms of individual genes, as previously revealed by conventional analysis in a small number of inbred mouse strains. Herein we used array-based comparative genomic hybridization (aCGH) to efficiently compare the NKC in 21 mouse strains to the reference C57BL/6 strain. By using unsupervised clustering methods, we could sort these variations into the same groups as determined by previous RFLP analyses of Nkrp1 and Ly49 genes. Prospective analyses of aCGH and RFLP data validated these relationships. Moreover, aCGH data predicted monoclonal antibody reactivity with an allospecific determinant on molecules expressed by NK cells. Taken together, these data demonstrate the structural variation in the NKC between mouse strains as well as the usefulness of aCGH in analysis of complex, polymorphic gene clusters.
KW - RFLPs
KW - array-based comparative genomic hybridization (aCGH)
KW - natural killer (NK) cells
KW - natural killer gene complex (NKC)
UR - http://www.scopus.com/inward/record.url?scp=78649710214&partnerID=8YFLogxK
U2 - 10.1038/gene.2010.48
DO - 10.1038/gene.2010.48
M3 - Article
C2 - 20861859
AN - SCOPUS:78649710214
SN - 1466-4879
VL - 11
SP - 637
EP - 648
JO - Genes and Immunity
JF - Genes and Immunity
IS - 8
ER -