A Mutation in KIR3DS1 That Results in Truncation and Lack of Cell Surface Expression

Authors

• Maureen P. Martin, National Cancer Institute at Frederick
• Veronique Pascal, National Cancer Institute at Frederick
• Meredith Yeager, National Cancer Institute at Frederick; National Cancer Institute at Rockville
• John Phair, Northwestern University Medical School
• Gregory D. Kirk, Johns Hopkins University
• Keith Hoots, Northwestern University Medical School
• Stephen J. O'Brien, National Cancer Institute at FrederickFollow
• Stephen K. Anderson, National Cancer Institute at Frederick
• Mary Carrington, National Cancer Institute at Frederick

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

Immunogenetics

ISSN

0093-7711

Publication Date

10-2007

Keywords

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

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.

Volume

59

Issue

10

First Page

823

Last Page

829

Comments

©Springer-Verlag 2007

Additional Comments

National Cancer Institute contract #: N01-CO-12400

NSUWorks Citation

Martin, Maureen P.; Veronique Pascal; Meredith Yeager; John Phair; Gregory D. Kirk; Keith Hoots; Stephen J. O'Brien; Stephen K. Anderson; and Mary Carrington. 2007. "A Mutation in KIR3DS1 That Results in Truncation and Lack of Cell Surface Expression." Immunogenetics 59, (10): 823-829. https://nsuworks.nova.edu/cnso_bio_facarticles/495