Evidence map›Paper›PMID 27486779›Full record

ArticleAmerican journal of human genetics2016

Defining KIR and HLA Class I Genotypes at Highest Resolution via High-Throughput Sequencing.

Paul J Norman, Jill A Hollenbach, Neda Nemat-Gorgani, Wesley M Marin, Steven J Norberg, Elham Ashouri, Jyothi Jayaraman, Emily E Wroblewski, John Trowsdale, Raja Rajalingam and 6 more

Open access · bronzeAbstract readValidation Study
In one paragraph

Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

116 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.

  1. Pooled it
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  10. A Scalable Framework for Comprehensive Typing of Polymorphic Immune Genes from Long-Read Data.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Paul J NormanDepartments of Structural Biology and Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: paul.norman@stanford.edu.
Jill A HollenbachDepartment of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Neda Nemat-GorganiDepartments of Structural Biology and Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Wesley M MarinDepartment of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Steven J NorbergIllumina Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
Elham AshouriDepartments of Structural Biology and Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Jyothi JayaramanDivision of Immunology, Department of Pathology and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 1QP, UK.
Emily E WroblewskiDepartments of Structural Biology and Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
John TrowsdaleDivision of Immunology, Department of Pathology and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 1QP, UK.
Raja RajalingamImmunogenetics and Transplantation Laboratory, University of California, San Francisco, San Francisco, CA 94143, USA.
Jorge R OksenbergDepartment of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Jacques ChiaroniUMR 7268 ADÉS, Aix-Marseille Université, l'Etablissement Français du Sang, Centre National de la Recherche Scientifique, 13344 Marseille, France.
Lisbeth A GuethleinDepartments of Structural Biology and Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
James A TraherneDivision of Immunology, Department of Pathology and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 1QP, UK.
Mostafa RonaghiIllumina Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
Peter ParhamDepartments of Structural Biology and Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Stanford University · USUniversity of California, San Francisco · USUniversity of Cambridge · GBIllumina (United States) · USAix-Marseille Université · FR

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Insights Into Immune-Related Diseases Born from Population GenomicsU01AI090905 · NIAID · UNIVERSITY OF COLORADO DENVER · PI Paul John Norman · 2010 to 2026
$10.9M
KIR association studies in neurological diseasesU19NS095774 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERNANDEZ-VINA, MARCELO, OKSENBERG, JORGE R. · 2015 to 2019
$7.0M
STRUCTURAL BIOLOGY OF HLA-A,B ANTIGENSR01AI017892 · NIAID · STANFORD UNIVERSITY · PI PARHAM, PETER R · 1985 to 2019
$6.1M
THE NATURE AND FUNCTION OF HLA-A,B,C POLYMORPHISMR01AI024258 · NIAID · STANFORD UNIVERSITY · PI PARHAM, PETER R · 1986 to 2020
$5.3M
Integrated Exchange & Storage of Current and Future-Generation Immunogenomic DataR01GM109030 · NIGMS · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI HOLLENBACH, JILL ALLISON, MACK, STEVEN JOHN · 2014 to 2016
$919k
NIAID NIH HHS R01 AI017892NIAID NIH HHS R01 AI024258NIAID NIH HHS U01 AI090905NIGMS NIH HHS R01 GM109030NIH HHS P51 OD011132NINDS NIH HHS U19 NS095774
6 · The paper itself

Abstract

The physiological functions of natural killer (NK) cells in human immunity and reproduction depend upon diverse interactions between killer cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands: HLA-A, HLA-B, and HLA-C. The genomic regions containing the KIR and HLA class I genes are unlinked, structurally complex, and highly polymorphic. They are also strongly associated with a wide spectrum of diseases, including infections, autoimmune disorders, cancers, and pregnancy disorders, as well as the efficacy of transplantation and other immunotherapies. To facilitate study of these extraordinary genes, we developed a method that captures, sequences, and analyzes the 13 KIR genes and HLA-A, HLA-B, and HLA-C from genomic DNA. We also devised a bioinformatics pipeline that attributes sequencing reads to specific KIR genes, determines copy number by read depth, and calls high-resolution genotypes for each KIR gene. We validated this method by using DNA from well-characterized cell lines, comparing it to established methods of HLA and KIR genotyping, and determining KIR genotypes from 1000 Genomes sequence data. This identified 116 previously uncharacterized KIR alleles, which were all demonstrated to be authentic by sequencing from source DNA via standard methods. Analysis of just two KIR genes showed that 22% of the 1000 Genomes individuals have a previously uncharacterized allele or a structural variant. The method we describe is suited to the large-scale analyses that are needed for characterizing human populations and defining the precise HLA and KIR factors associated with disease. The methods are applicable to other highly polymorphic genes.

Indexed as

GenotypeAllelesGene DosageGenes, MHC Class IGenome, HumanHaplotypesHigh-Throughput Nucleotide SequencingHLA-A AntigensHLA-B AntigensHLA-C AntigensHumansPolymorphism, GeneticReceptors, KIRHLA-A AntigensHLA-B AntigensHLA-C AntigensReceptors, KIRgene content diversityhighly polymorphicHLA class IimmunityKIR

Identifiers

PMID27486779
PMCPMC4974113
OpenAlexW2476725372

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.