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A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti-Xga production

Lee, Yan Quan LU ; Storry, Jill R LU ; Karamatic Crew, Vanja; Halverson, Gregory R; Thornton, Nicole and Olsson, Martin L LU (2019) In Transfusion 59(5). p.1843-1849
Abstract

BACKGROUND: The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xga .

STUDY DESIGN AND METHODS: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples.

RESULTS:... (More)

BACKGROUND: The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xga .

STUDY DESIGN AND METHODS: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples.

RESULTS: Investigation of one gDNA sample revealed a 114-kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555-bp fragment bridging this deletion was amplified to confirm its presence. Another deletion-specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence.

CONCLUSION: We identified a large deletion on the X chromosome, resulting in a true, tissue-wide Xgnull phenotype. This deletion was found in 10 of 11 anti-Xga makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Transfusion
volume
59
issue
5
pages
1843 - 1849
publisher
Wiley-Blackwell
external identifiers
  • scopus:85063792523
ISSN
1537-2995
DOI
10.1111/trf.15242
language
English
LU publication?
yes
id
f7cd9f22-8b44-4fc8-b0e8-4b0457af12b0
date added to LUP
2019-04-15 16:27:21
date last changed
2019-06-27 13:58:37
@article{f7cd9f22-8b44-4fc8-b0e8-4b0457af12b0,
  abstract     = {<p>BACKGROUND: The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xga .</p><p>STUDY DESIGN AND METHODS: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples.</p><p>RESULTS: Investigation of one gDNA sample revealed a 114-kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555-bp fragment bridging this deletion was amplified to confirm its presence. Another deletion-specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence.</p><p>CONCLUSION: We identified a large deletion on the X chromosome, resulting in a true, tissue-wide Xgnull phenotype. This deletion was found in 10 of 11 anti-Xga makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored.</p>},
  author       = {Lee, Yan Quan and Storry, Jill R and Karamatic Crew, Vanja and Halverson, Gregory R and Thornton, Nicole and Olsson, Martin L},
  issn         = {1537-2995},
  language     = {eng},
  month        = {04},
  number       = {5},
  pages        = {1843--1849},
  publisher    = {Wiley-Blackwell},
  series       = {Transfusion},
  title        = {A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti-Xga production},
  url          = {http://dx.doi.org/10.1111/trf.15242},
  volume       = {59},
  year         = {2019},
}