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Two previously proposed P-1/P-2-differentiating and nine novel polymorphisms at the A4GALT (P-k) locus do not correlate with the presence of the P1 blood group antigen

Hellberg, Åsa LU ; Chester, Alan LU and Olsson, Martin L LU (2005) In BMC Genetics 6(49).
Abstract
Background: The molecular genetics of the P blood group system and the absence of P1 antigen in the p phenotype are still enigmatic. One theory proposes that the same gene encodes for both the P1 and P-k glycosyltransferases, but no polymorphisms in the coding region of the P-k gene explain the P-1/P-2 phenotypes. We investigated the potential regulatory regions up- and downstream of the A4GALT (P-k) gene exons. Results: P-1 (n = 18) and P-2 (n = 9) samples from donors of mainly Swedish descent were analysed by direct sequencing of PCR-amplified 5'- and 3'-fragments surrounding the P-k coding region. Seventy-eight P-1 and P-2 samples were investigated with PCR using allele-specific primers (ASP) for two polymorphisms previously proposed as... (More)
Background: The molecular genetics of the P blood group system and the absence of P1 antigen in the p phenotype are still enigmatic. One theory proposes that the same gene encodes for both the P1 and P-k glycosyltransferases, but no polymorphisms in the coding region of the P-k gene explain the P-1/P-2 phenotypes. We investigated the potential regulatory regions up- and downstream of the A4GALT (P-k) gene exons. Results: P-1 (n = 18) and P-2 (n = 9) samples from donors of mainly Swedish descent were analysed by direct sequencing of PCR-amplified 5'- and 3'-fragments surrounding the P-k coding region. Seventy-eight P-1 and P-2 samples were investigated with PCR using allele-specific primers (ASP) for two polymorphisms previously proposed as P-2-related genetic markers(- 551_-550insC, -160A>G). Haplotype analysis of single nucleotide polymorphisms was also performed with PCR-ASP. In similar to 1.5 kbp of the 3'-untranslated region one new insertion and four new substitutions compared to a GenBank sequence (AL049757) were found. In addition to the polymorphisms at positions - 550 and - 160, one insertion, two deletions and one substitution were found in similar to 1.0 kbp of the 5'-upstream region. All 20 P-2 samples investigated with PCR-ASP were homozygous for -550insC. However, so were 18 of the 58 P-1 samples investigated. Both the 20 P-2 and the 18 P-1 samples were also homozygous for -160G. Conclusion: The proposed P-2-specific polymorphisms, -551_-550insC and -160G, found in P-2 samples in a Japanese study were found here in homozygous form in both P-1 and P-2 donors. Since P-2 is the null allele in the P blood group system it is difficult to envision how these mutations would cause the P-2 phenotype. None of the novel polymorphisms reported in this study correlated with P-1/P-2 status and the P1/p mystery remains unsolved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Genetics
volume
6
issue
49
publisher
BioMed Central
external identifiers
  • pmid:16212661
  • wos:000233136300001
  • scopus:27644594291
ISSN
1471-2156
DOI
10.1186/1471-2156-6-49
language
English
LU publication?
yes
id
06faa8a9-205e-4f2c-8c51-0f38fab567a0 (old id 214024)
date added to LUP
2007-09-28 09:04:37
date last changed
2017-07-23 04:39:58
@article{06faa8a9-205e-4f2c-8c51-0f38fab567a0,
  abstract     = {Background: The molecular genetics of the P blood group system and the absence of P1 antigen in the p phenotype are still enigmatic. One theory proposes that the same gene encodes for both the P1 and P-k glycosyltransferases, but no polymorphisms in the coding region of the P-k gene explain the P-1/P-2 phenotypes. We investigated the potential regulatory regions up- and downstream of the A4GALT (P-k) gene exons. Results: P-1 (n = 18) and P-2 (n = 9) samples from donors of mainly Swedish descent were analysed by direct sequencing of PCR-amplified 5'- and 3'-fragments surrounding the P-k coding region. Seventy-eight P-1 and P-2 samples were investigated with PCR using allele-specific primers (ASP) for two polymorphisms previously proposed as P-2-related genetic markers(- 551_-550insC, -160A>G). Haplotype analysis of single nucleotide polymorphisms was also performed with PCR-ASP. In similar to 1.5 kbp of the 3'-untranslated region one new insertion and four new substitutions compared to a GenBank sequence (AL049757) were found. In addition to the polymorphisms at positions - 550 and - 160, one insertion, two deletions and one substitution were found in similar to 1.0 kbp of the 5'-upstream region. All 20 P-2 samples investigated with PCR-ASP were homozygous for -550insC. However, so were 18 of the 58 P-1 samples investigated. Both the 20 P-2 and the 18 P-1 samples were also homozygous for -160G. Conclusion: The proposed P-2-specific polymorphisms, -551_-550insC and -160G, found in P-2 samples in a Japanese study were found here in homozygous form in both P-1 and P-2 donors. Since P-2 is the null allele in the P blood group system it is difficult to envision how these mutations would cause the P-2 phenotype. None of the novel polymorphisms reported in this study correlated with P-1/P-2 status and the P1/p mystery remains unsolved.},
  author       = {Hellberg, Åsa and Chester, Alan and Olsson, Martin L},
  issn         = {1471-2156},
  language     = {eng},
  number       = {49},
  publisher    = {BioMed Central},
  series       = {BMC Genetics},
  title        = {Two previously proposed P-1/P-2-differentiating and nine novel polymorphisms at the A4GALT (P-k) locus do not correlate with the presence of the P1 blood group antigen},
  url          = {http://dx.doi.org/10.1186/1471-2156-6-49},
  volume       = {6},
  year         = {2005},
}