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
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.
(Less)
- author
- Wester, Elisabet Sjöberg
LU
; Gustafsson, Julia
; Snell, Beverly
; Spruell, Peggy
; Hellberg, Åsa
LU
; Olsson, Martin L.
LU
and Storry, Jill R.
LU
- organization
- publishing date
- 2009
- 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
-
- scopus:77951851940
- pmid:20406024
- 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
- 2024-06-01 13:54:31
@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>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.</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}},
}