A mutation in KIR3DS1 that results in truncation and lack of cell surface expression

Maureen P. Martin; Véronique Pascal; Meredith Yeager; John Phair; Gregory D. Kirk; Keith Hoots; Stephen J. O'Brien; Stephen K. Anderson; Mary Carrington

doi:10.1007/s00251-007-0240-8

A mutation in KIR3DS1 that results in truncation and lack of cell surface expression

Maureen P. Martin, Véronique Pascal, Meredith Yeager, John Phair, Gregory D. Kirk, Keith Hoots, Stephen J. O'Brien, Stephen K. Anderson, Mary Carrington^*

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The KIR gene cluster exhibits a high degree of polymorphism in terms of gene content as well as allelic polymorphism, and data suggest that it is evolving rapidly. The KIR3DL1 locus is one of the most polymorphic loci within this cluster and is unique in that it encodes an activating receptor KIR3DS1, as well as multiple inhibitory KIR3DL1 allotypes. Because KIR3DS1 has been implicated in a number of diseases, we tested for the presence of KIR3DS1 variants that might affect its expression and activating capacity. Preliminary FACS analysis indicated that indeed some individuals with the KIR3DS1 allele showed no cell surface expression of the molecule. Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 (which encodes the D1 extracellular domain), resulting in a premature stop codon. We subsequently genotyped 3,960 unrelated individuals and determined the frequencies of this allele across geographically distinct world populations. The data indicate that the null KIR3DS1 allele is uncommon, arose on a single haplotype, and spread across geographically distinct populations.

Original language	English (US)
Pages (from-to)	823-829
Number of pages	7
Journal	Immunogenetics
Volume	59
Issue number	10
DOIs	https://doi.org/10.1007/s00251-007-0240-8
State	Published - Oct 2007

Funding

Acknowledgments This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Keywords

Cell surface expression
Human Genome Diversity Panel (HGDP)
KIR expression
KIR gene polymorphism
KIR3DS/L1 locus
KIR3DS1
Truncation

ASJC Scopus subject areas

Genetics
Immunology

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10.1007/s00251-007-0240-8

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title = "A mutation in KIR3DS1 that results in truncation and lack of cell surface expression",

abstract = "The KIR gene cluster exhibits a high degree of polymorphism in terms of gene content as well as allelic polymorphism, and data suggest that it is evolving rapidly. The KIR3DL1 locus is one of the most polymorphic loci within this cluster and is unique in that it encodes an activating receptor KIR3DS1, as well as multiple inhibitory KIR3DL1 allotypes. Because KIR3DS1 has been implicated in a number of diseases, we tested for the presence of KIR3DS1 variants that might affect its expression and activating capacity. Preliminary FACS analysis indicated that indeed some individuals with the KIR3DS1 allele showed no cell surface expression of the molecule. Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 (which encodes the D1 extracellular domain), resulting in a premature stop codon. We subsequently genotyped 3,960 unrelated individuals and determined the frequencies of this allele across geographically distinct world populations. The data indicate that the null KIR3DS1 allele is uncommon, arose on a single haplotype, and spread across geographically distinct populations.",

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note = "Funding Information: Acknowledgments This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.",

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AU - Hoots, Keith

AU - O'Brien, Stephen J.

AU - Anderson, Stephen K.

AU - Carrington, Mary

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N2 - The KIR gene cluster exhibits a high degree of polymorphism in terms of gene content as well as allelic polymorphism, and data suggest that it is evolving rapidly. The KIR3DL1 locus is one of the most polymorphic loci within this cluster and is unique in that it encodes an activating receptor KIR3DS1, as well as multiple inhibitory KIR3DL1 allotypes. Because KIR3DS1 has been implicated in a number of diseases, we tested for the presence of KIR3DS1 variants that might affect its expression and activating capacity. Preliminary FACS analysis indicated that indeed some individuals with the KIR3DS1 allele showed no cell surface expression of the molecule. Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 (which encodes the D1 extracellular domain), resulting in a premature stop codon. We subsequently genotyped 3,960 unrelated individuals and determined the frequencies of this allele across geographically distinct world populations. The data indicate that the null KIR3DS1 allele is uncommon, arose on a single haplotype, and spread across geographically distinct populations.

AB - The KIR gene cluster exhibits a high degree of polymorphism in terms of gene content as well as allelic polymorphism, and data suggest that it is evolving rapidly. The KIR3DL1 locus is one of the most polymorphic loci within this cluster and is unique in that it encodes an activating receptor KIR3DS1, as well as multiple inhibitory KIR3DL1 allotypes. Because KIR3DS1 has been implicated in a number of diseases, we tested for the presence of KIR3DS1 variants that might affect its expression and activating capacity. Preliminary FACS analysis indicated that indeed some individuals with the KIR3DS1 allele showed no cell surface expression of the molecule. Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 (which encodes the D1 extracellular domain), resulting in a premature stop codon. We subsequently genotyped 3,960 unrelated individuals and determined the frequencies of this allele across geographically distinct world populations. The data indicate that the null KIR3DS1 allele is uncommon, arose on a single haplotype, and spread across geographically distinct populations.

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A mutation in KIR3DS1 that results in truncation and lack of cell surface expression

Abstract

Funding

Keywords

ASJC Scopus subject areas

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