Heterogeneity of human Neutrophil CD177 expression results from CD177P1 Pseudogene Conversion

Wu, Zuopeng, Liang, Rong, Ohnesorg, Thomas, Cho, Vicky, Lam, Wesley, Abhayaratna, Walter P., Gatenby, Paul A., Perera, Chandima, Zhang, Yafei, Whittle, Belinda, Sinclair, Andrew, Goodnow, Christopher C., Field, Matthew, Andrews, T. Daniel, and Cook, Matthew C. (2016) Heterogeneity of human Neutrophil CD177 expression results from CD177P1 Pseudogene Conversion. PLOS Genetics, 12 (5). e1006067. pp. 1-22.

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Abstract

Most humans harbor both CD177neg and CD177pos neutrophils but 1–10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1), which appears to have resulted from allelic gene conversion. In CD177 expressing individuals the CD177 locus contains both CD177P1 and CD177 sequences. The proportion of CD177hi neutrophils in the blood is a heritable trait. Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed. Human neutrophil heterogeneity for CD177 expression arises by ectopic allelic conversion. Resolution of the genetic basis of CD177null phenotype identifies a method for screening for individuals at risk of CD177 isoimmunisation.

Item ID: 44612
Item Type: Article (Research - C1)
ISSN: 1553-7404
Additional Information:

© 2016 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: Canberra Hospital Private Practice Fund, National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Fellowship 585490, NHMRC Grant 1016953
Date Deposited: 13 Jul 2016 03:18
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110706 Immunogenetics (incl Genetic Immunology) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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