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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/214024
- author
- Hellberg, Åsa
LU
; Chester, Alan
LU
and Olsson, Martin L
LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Genetics
- volume
- 6
- issue
- 49
- publisher
- BioMed Central (BMC)
- 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
- 2016-04-01 16:19:56
- date last changed
- 2022-01-28 18:55:55
@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 (BMC)}},
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}},
doi = {{10.1186/1471-2156-6-49}},
volume = {{6}},
year = {{2005}},
}