Nature of allelic sequence polymorphism at the KIR3DL3 locus

Des C Jones, Susan E Hiby, Ashley Moffett, John Trowsdale, Neil Thomas Young

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

KIR3DL3 is a framework gene of the Leukocyte Receptor Complex, present in all individuals and haplotypes analysed to date. We describe 17 novel KIR3DL3 alleles, including seven single nucleotide polymorphic (SNP) positions within the coding region. Sequence variation within introns included a VNTR within intron 1. As KIR3DL3 mRNA is known to be expressed in decidual NK cells, we investigated the impact of KIR3DL3 allelic variation on pre-eclampsia. No statistical difference in allele frequency or polymorphism was observed between pre-eclampsia patient and control cohorts. Linkage disequilibrium (LD) analysis of exonic SNPs suggested that recombination may be a mechanism of generating sequence diversity within KIR3DL3. A potential recombination hotspot was located within intron 5. A strong LD was detected between polymorphism in exon 6 of KIR3DL3 and the KIR gene -2DL3 or -2DS2 loci, which define the centromeric end of two main haplotypes (A and B) of the KIR cluster. Comparison of primate KIR sequences indicated that the Ig domains of KIR3DL3 are highly conserved between chimpanzee, gorilla and humans. Investigation of KIR3DL3 dN/dS ratios indicated a greater level of synonymous mutations consistent with purifying selection, although positive selection was detected acting on two sites within the stem region.
Original languageEnglish
Pages (from-to)614-627
Number of pages14
JournalImmunogenetics
Volume58
Issue number8
DOIs
Publication statusPublished - 2006

Fingerprint

Introns
Linkage Disequilibrium
Pre-Eclampsia
Haplotypes
Genetic Recombination
Gorilla gorilla
Pan troglodytes
Gene Frequency
Natural Killer Cells
Primates
Genes
Single Nucleotide Polymorphism
Exons
Leukocytes
Nucleotides
Alleles
Messenger RNA
Immunoglobulin Domains
Silent Mutation

Keywords

  • Alleles
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Variation
  • Humans
  • Introns
  • Killer Cells, Natural
  • Linkage Disequilibrium
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Pre-Eclampsia
  • Pregnancy
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL3
  • Recombination, Genetic
  • Selection, Genetic

Cite this

Jones, D. C., Hiby, S. E., Moffett, A., Trowsdale, J., & Young, N. T. (2006). Nature of allelic sequence polymorphism at the KIR3DL3 locus. Immunogenetics, 58(8), 614-627. https://doi.org/10.1007/s00251-006-0130-5

Nature of allelic sequence polymorphism at the KIR3DL3 locus. / Jones, Des C; Hiby, Susan E; Moffett, Ashley; Trowsdale, John; Young, Neil Thomas.

In: Immunogenetics, Vol. 58, No. 8, 2006, p. 614-627.

Research output: Contribution to journalArticle

Jones, DC, Hiby, SE, Moffett, A, Trowsdale, J & Young, NT 2006, 'Nature of allelic sequence polymorphism at the KIR3DL3 locus', Immunogenetics, vol. 58, no. 8, pp. 614-627. https://doi.org/10.1007/s00251-006-0130-5
Jones DC, Hiby SE, Moffett A, Trowsdale J, Young NT. Nature of allelic sequence polymorphism at the KIR3DL3 locus. Immunogenetics. 2006;58(8):614-627. https://doi.org/10.1007/s00251-006-0130-5
Jones, Des C ; Hiby, Susan E ; Moffett, Ashley ; Trowsdale, John ; Young, Neil Thomas. / Nature of allelic sequence polymorphism at the KIR3DL3 locus. In: Immunogenetics. 2006 ; Vol. 58, No. 8. pp. 614-627.
@article{6cc7b76aeb9347169d674c7d8de55663,
title = "Nature of allelic sequence polymorphism at the KIR3DL3 locus",
abstract = "KIR3DL3 is a framework gene of the Leukocyte Receptor Complex, present in all individuals and haplotypes analysed to date. We describe 17 novel KIR3DL3 alleles, including seven single nucleotide polymorphic (SNP) positions within the coding region. Sequence variation within introns included a VNTR within intron 1. As KIR3DL3 mRNA is known to be expressed in decidual NK cells, we investigated the impact of KIR3DL3 allelic variation on pre-eclampsia. No statistical difference in allele frequency or polymorphism was observed between pre-eclampsia patient and control cohorts. Linkage disequilibrium (LD) analysis of exonic SNPs suggested that recombination may be a mechanism of generating sequence diversity within KIR3DL3. A potential recombination hotspot was located within intron 5. A strong LD was detected between polymorphism in exon 6 of KIR3DL3 and the KIR gene -2DL3 or -2DS2 loci, which define the centromeric end of two main haplotypes (A and B) of the KIR cluster. Comparison of primate KIR sequences indicated that the Ig domains of KIR3DL3 are highly conserved between chimpanzee, gorilla and humans. Investigation of KIR3DL3 dN/dS ratios indicated a greater level of synonymous mutations consistent with purifying selection, although positive selection was detected acting on two sites within the stem region.",
keywords = "Alleles, Case-Control Studies, Cohort Studies, Female, Gene Frequency, Genetic Variation, Humans, Introns, Killer Cells, Natural, Linkage Disequilibrium, Phylogeny, Polymorphism, Single Nucleotide, Pre-Eclampsia, Pregnancy, Receptors, Immunologic, Receptors, KIR, Receptors, KIR2DL3, Recombination, Genetic, Selection, Genetic",
author = "Jones, {Des C} and Hiby, {Susan E} and Ashley Moffett and John Trowsdale and Young, {Neil Thomas}",
year = "2006",
doi = "10.1007/s00251-006-0130-5",
language = "English",
volume = "58",
pages = "614--627",
journal = "Immunogenetics",
issn = "0093-7711",
publisher = "Springer Verlag",
number = "8",

}

TY - JOUR

T1 - Nature of allelic sequence polymorphism at the KIR3DL3 locus

AU - Jones, Des C

AU - Hiby, Susan E

AU - Moffett, Ashley

AU - Trowsdale, John

AU - Young, Neil Thomas

PY - 2006

Y1 - 2006

N2 - KIR3DL3 is a framework gene of the Leukocyte Receptor Complex, present in all individuals and haplotypes analysed to date. We describe 17 novel KIR3DL3 alleles, including seven single nucleotide polymorphic (SNP) positions within the coding region. Sequence variation within introns included a VNTR within intron 1. As KIR3DL3 mRNA is known to be expressed in decidual NK cells, we investigated the impact of KIR3DL3 allelic variation on pre-eclampsia. No statistical difference in allele frequency or polymorphism was observed between pre-eclampsia patient and control cohorts. Linkage disequilibrium (LD) analysis of exonic SNPs suggested that recombination may be a mechanism of generating sequence diversity within KIR3DL3. A potential recombination hotspot was located within intron 5. A strong LD was detected between polymorphism in exon 6 of KIR3DL3 and the KIR gene -2DL3 or -2DS2 loci, which define the centromeric end of two main haplotypes (A and B) of the KIR cluster. Comparison of primate KIR sequences indicated that the Ig domains of KIR3DL3 are highly conserved between chimpanzee, gorilla and humans. Investigation of KIR3DL3 dN/dS ratios indicated a greater level of synonymous mutations consistent with purifying selection, although positive selection was detected acting on two sites within the stem region.

AB - KIR3DL3 is a framework gene of the Leukocyte Receptor Complex, present in all individuals and haplotypes analysed to date. We describe 17 novel KIR3DL3 alleles, including seven single nucleotide polymorphic (SNP) positions within the coding region. Sequence variation within introns included a VNTR within intron 1. As KIR3DL3 mRNA is known to be expressed in decidual NK cells, we investigated the impact of KIR3DL3 allelic variation on pre-eclampsia. No statistical difference in allele frequency or polymorphism was observed between pre-eclampsia patient and control cohorts. Linkage disequilibrium (LD) analysis of exonic SNPs suggested that recombination may be a mechanism of generating sequence diversity within KIR3DL3. A potential recombination hotspot was located within intron 5. A strong LD was detected between polymorphism in exon 6 of KIR3DL3 and the KIR gene -2DL3 or -2DS2 loci, which define the centromeric end of two main haplotypes (A and B) of the KIR cluster. Comparison of primate KIR sequences indicated that the Ig domains of KIR3DL3 are highly conserved between chimpanzee, gorilla and humans. Investigation of KIR3DL3 dN/dS ratios indicated a greater level of synonymous mutations consistent with purifying selection, although positive selection was detected acting on two sites within the stem region.

KW - Alleles

KW - Case-Control Studies

KW - Cohort Studies

KW - Female

KW - Gene Frequency

KW - Genetic Variation

KW - Humans

KW - Introns

KW - Killer Cells, Natural

KW - Linkage Disequilibrium

KW - Phylogeny

KW - Polymorphism, Single Nucleotide

KW - Pre-Eclampsia

KW - Pregnancy

KW - Receptors, Immunologic

KW - Receptors, KIR

KW - Receptors, KIR2DL3

KW - Recombination, Genetic

KW - Selection, Genetic

U2 - 10.1007/s00251-006-0130-5

DO - 10.1007/s00251-006-0130-5

M3 - Article

C2 - 16823588

VL - 58

SP - 614

EP - 627

JO - Immunogenetics

JF - Immunogenetics

SN - 0093-7711

IS - 8

ER -