Extensive Variation in Gene Copy Number at the Killer Immunoglobulin-Like Receptor Locus in Humans

نویسندگان

  • Sanne Vendelbosch
  • Martin de Boer
  • Remko A. T. W. Gouw
  • Cynthia K. Y. Ho
  • Judy Geissler
  • Wendy T. N. Swelsen
  • Michael J. Moorhouse
  • Neubury M. Lardy
  • Dirk Roos
  • Timo K. van den Berg
  • Taco W. Kuijpers
چکیده

Killer immunoglobulin-like receptors (KIRs) are involved in the regulation of natural killer cell cytotoxicity. Within the human genome seventeen KIR genes are present, which all contain a large number of allelic variants. The high level of homology among KIR genes has hampered KIR genotyping in larger cohorts, and determination of gene copy number variation (CNV) has been difficult. We have designed a multiplex ligation-dependent probe amplification (MLPA) technique for genotyping and CNV determination in one single assay and validated the results by next-generation sequencing and with a KIR gene-specific short tandem repeat assay. In this way, we demonstrate in a cohort of 120 individuals a high level of CNV for all KIR genes except for the framework genes KIR3DL3 and KIR3DL2. Application of our MLPA assay in segregation analyses of families from the Centre d'Etude du Polymorphisme Humaine, previously KIR-genotyped by classical techniques, confirmed an earlier reported duplication and resulted in the identification of a novel duplication event in one of these families. In summary, our KIR MLPA assay allows rapid and accurate KIR genotyping and CNV detection, thus rendering improved transplantation programs and oncology treatment feasible, and enables more detailed studies on the role of KIRs in human (auto)immunity and infectious disease.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

ASSOCIATION OF KILLER IMMUNOGLOBULIN IIKE RECEPTOR (KIR) GENE POLYMORPHISMS WITH TYPE 1 DIABETES: A META-ANALYSIS

English version of this article has been published in “ journal of diabetes & metabolic disorders “ with both editor-in-chiefs agreement; aims to be available for Persian language readers; http://doi.org/10.1111/j.1399-039.2007.00956.x.

متن کامل

Inhibitory Killer Cell Immunoglobulin-Like Receptor KIR3DL1 in Combination with HLA-B Bw4iso Protect against Ankylosing Spondylitis

Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLAC and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing spondylitis (AS) susceptibility, alone or in combination. Methods: We typed 4...

متن کامل

Copy Number Variation of KIR Genes Influences HIV-1 Control

A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regula...

متن کامل

BIRC5 Genomic Copy Number Variation in Early-Onset Breast Cancer

Background: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene is an inhibitor of apoptosis that expresses in human embryonic tissues but it is absent in most healthy adult tissues. The copy number of BIRC5 has been indicated to be highly increased in tumor tissues; however, its association with the age of onset in breast cancer is not well understood. Methods: Forty tumor tiss...

متن کامل

Killer Cell Immunoglobulin-Like Receptors Influence the Innate and Adaptive Immune Responses

Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2013