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A simple screening assay for the most common JK*0 alleles revealed compound heterozygosity in Jk(a-b-) probands from Guam

Wester, Elisabet Sjöberg LU ; Gustafsson, Julia ; Snell, Beverly ; Spruell, Peggy ; Hellberg, Åsa LU ; Olsson, Martin L. LU orcid and Storry, Jill R. LU (2009) In Immunohematology 25(4). p.165-169
Abstract

The Jk(a-b-) phenotype results from alterations in the JK gene and is characterized by absence of the RBC urea transporter in the cell membrane. The frequency of Jk(a-b-) varies among populations, but this phenotype is most commonly found in people of Polynesian and Finnish descent. Although rare, Jk(a-b-) individuals present a clinical challenge because anti-Jk3 is produced readily in response to transfusion and pregnancy, and Jk(a-b-) blood is not routinely available. Identification of Jk(a-b-) patients and donors is most often performed serologically. However, ten JK*o alleles have been identified, and this information can be used in DNA-based typing. We selected five JK*o alleles that had been encountered by our reference laboratory... (More)

The Jk(a-b-) phenotype results from alterations in the JK gene and is characterized by absence of the RBC urea transporter in the cell membrane. The frequency of Jk(a-b-) varies among populations, but this phenotype is most commonly found in people of Polynesian and Finnish descent. Although rare, Jk(a-b-) individuals present a clinical challenge because anti-Jk3 is produced readily in response to transfusion and pregnancy, and Jk(a-b-) blood is not routinely available. Identification of Jk(a-b-) patients and donors is most often performed serologically. However, ten JK*o alleles have been identified, and this information can be used in DNA-based typing. We selected five JK*o alleles that had been encountered by our reference laboratory in two or more samples from unrelated individuals and designed an allele-specific primer PCR assay for use as an initial screening tool. After in-house validation, we tested genomic DNA from a family: a mother and her two sons referred to us for genetic investigation of their Jk(a-b-) phenotypes. Two different nucleotide substitutions, -1g>a in intron 5 (IVS5) and 956C>T in exon 10, originally associated with Polynesian and Indian/African populations respectively, were identified in the family. The mother and one son were compound heterozygotes, and the second son was homozygous for IVS5-1g>a. We conclude that the effort to design and validate such a screening assay was cost-efficient when compared with DNA sequencing costs. Furthermore, selection of the more common JK*o mutations was a practical approach that resulted in rapid identification of the genetic bases behind the Jk(a-b-) phenotypes in this unusual family. Although an obvious target for eventual inclusion into high-throughput genotyping platforms for clinical diagnostic services, current systems are very limited. Our approach provides a simple and inexpensive method for the identification of these rare alleles.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
JK blood group system, Molecular basis, Null phenotypes, PCR-ASP
in
Immunohematology
volume
25
issue
4
pages
5 pages
publisher
American Red Cross
external identifiers
  • pmid:20406024
  • scopus:77951851940
ISSN
0894-203X
language
English
LU publication?
yes
additional info
Copyright: Copyright 2015 Elsevier B.V., All rights reserved.
id
b4cbc488-3680-46e1-a3c2-4d9ef588fda6
alternative location
https://www.exeley.com/exeley/journals/immunohematology/25/4/pdf/10.21307_immunohematology-2019-250.pdf
date added to LUP
2021-08-04 11:54:45
date last changed
2022-04-19 07:27:21
@article{b4cbc488-3680-46e1-a3c2-4d9ef588fda6,
  abstract     = {{<p>The Jk(a-b-) phenotype results from alterations in the JK gene and is characterized by absence of the RBC urea transporter in the cell membrane. The frequency of Jk(a-b-) varies among populations, but this phenotype is most commonly found in people of Polynesian and Finnish descent. Although rare, Jk(a-b-) individuals present a clinical challenge because anti-Jk3 is produced readily in response to transfusion and pregnancy, and Jk(a-b-) blood is not routinely available. Identification of Jk(a-b-) patients and donors is most often performed serologically. However, ten JK*o alleles have been identified, and this information can be used in DNA-based typing. We selected five JK*o alleles that had been encountered by our reference laboratory in two or more samples from unrelated individuals and designed an allele-specific primer PCR assay for use as an initial screening tool. After in-house validation, we tested genomic DNA from a family: a mother and her two sons referred to us for genetic investigation of their Jk(a-b-) phenotypes. Two different nucleotide substitutions, -1g&gt;a in intron 5 (IVS5) and 956C&gt;T in exon 10, originally associated with Polynesian and Indian/African populations respectively, were identified in the family. The mother and one son were compound heterozygotes, and the second son was homozygous for IVS5-1g&gt;a. We conclude that the effort to design and validate such a screening assay was cost-efficient when compared with DNA sequencing costs. Furthermore, selection of the more common JK*o mutations was a practical approach that resulted in rapid identification of the genetic bases behind the Jk(a-b-) phenotypes in this unusual family. Although an obvious target for eventual inclusion into high-throughput genotyping platforms for clinical diagnostic services, current systems are very limited. Our approach provides a simple and inexpensive method for the identification of these rare alleles.</p>}},
  author       = {{Wester, Elisabet Sjöberg and Gustafsson, Julia and Snell, Beverly and Spruell, Peggy and Hellberg, Åsa and Olsson, Martin L. and Storry, Jill R.}},
  issn         = {{0894-203X}},
  keywords     = {{JK blood group system; Molecular basis; Null phenotypes; PCR-ASP}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{165--169}},
  publisher    = {{American Red Cross}},
  series       = {{Immunohematology}},
  title        = {{A simple screening assay for the most common JK*0 alleles revealed compound heterozygosity in Jk(a-b-) probands from Guam}},
  url          = {{https://www.exeley.com/exeley/journals/immunohematology/25/4/pdf/10.21307_immunohematology-2019-250.pdf}},
  volume       = {{25}},
  year         = {{2009}},
}