Thorough analysis of unorthodox ABO deletions called by the 1000 Genomes project
Möller, M LU
; Hellberg, Å
LU
and Olsson, M L
LU
(2018)
In Vox Sanguinis
113(2).
p.185-197
- Abstract
BACKGROUND AND OBJECTIVES: ABO remains the clinically most important blood group system, but despite earlier extensive research, significant findings are still being made. The vast majority of catalogued ABO null alleles are based on the c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are rare. While analysing the data set from the 1000 Genomes (1000G) project, we encountered two previously uncharacterized deletions, which needed further exploration.
MATERIALS AND METHODS: The Erythrogene database, complemented with bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G. DNA samples from selected 1000G donors and African blood donors were examined by allele-specific PCR and... (More)
BACKGROUND AND OBJECTIVES: ABO remains the clinically most important blood group system, but despite earlier extensive research, significant findings are still being made. The vast majority of catalogued ABO null alleles are based on the c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are rare. While analysing the data set from the 1000 Genomes (1000G) project, we encountered two previously uncharacterized deletions, which needed further exploration.
MATERIALS AND METHODS: The Erythrogene database, complemented with bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G. DNA samples from selected 1000G donors and African blood donors were examined by allele-specific PCR and Sanger sequencing to characterize predicted deletions.
RESULTS: A 5821-bp deletion encompassing exons 5-7 was called in twenty 1000G individuals, predominantly Africans. This allele was confirmed and its exact deletion point defined by bioinformatic analyses and in vitro experiments. A PCR assay was developed, and screening of African samples revealed three donors heterozygous for this deletion, which was thereby phenotypically established as an O allele. Analysis of upstream genetic markers indicated an ancestral origin from ABO*O.01.02. We estimate this deletion as the 3rd most common mechanism behind O alleles. A 24-bp deletion was called in nine individuals and showed greater diversity regarding ethnic distribution and allelic background. It could neither be confirmed by in silico nor in vitro experiments.
CONCLUSION: A previously uncharacterized ABO deletion among Africans was comprehensively mapped and a genotyping strategy devised. The false prediction of another deletion emphasizes the need for cautious interpretation of NGS data and calls for strict validation routines.
(Less)
- author
- Möller, M
LU
; Hellberg, Å
LU
and Olsson, M L
LU
- organization
- publishing date
- 2018-02-14
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Vox Sanguinis
- volume
- 113
- issue
- 2
- pages
- 13 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:29214632
- scopus:85042132866
- ISSN
- 1423-0410
- DOI
- 10.1111/vox.12613
- project
- Bioinformatic Analysis of Blood Group Genomics
- language
- English
- LU publication?
- yes
- id
- 0e272d52-c7b9-4e93-b5ce-b6d221979d9f
- date added to LUP
- 2018-02-15 18:44:11
- date last changed
- 2024-03-18 05:11:11
@article{0e272d52-c7b9-4e93-b5ce-b6d221979d9f,
abstract = {{<p>BACKGROUND AND OBJECTIVES: ABO remains the clinically most important blood group system, but despite earlier extensive research, significant findings are still being made. The vast majority of catalogued ABO null alleles are based on the c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are rare. While analysing the data set from the 1000 Genomes (1000G) project, we encountered two previously uncharacterized deletions, which needed further exploration.</p><p>MATERIALS AND METHODS: The Erythrogene database, complemented with bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G. DNA samples from selected 1000G donors and African blood donors were examined by allele-specific PCR and Sanger sequencing to characterize predicted deletions.</p><p>RESULTS: A 5821-bp deletion encompassing exons 5-7 was called in twenty 1000G individuals, predominantly Africans. This allele was confirmed and its exact deletion point defined by bioinformatic analyses and in vitro experiments. A PCR assay was developed, and screening of African samples revealed three donors heterozygous for this deletion, which was thereby phenotypically established as an O allele. Analysis of upstream genetic markers indicated an ancestral origin from ABO*O.01.02. We estimate this deletion as the 3rd most common mechanism behind O alleles. A 24-bp deletion was called in nine individuals and showed greater diversity regarding ethnic distribution and allelic background. It could neither be confirmed by in silico nor in vitro experiments.</p><p>CONCLUSION: A previously uncharacterized ABO deletion among Africans was comprehensively mapped and a genotyping strategy devised. The false prediction of another deletion emphasizes the need for cautious interpretation of NGS data and calls for strict validation routines.</p>}},
author = {{Möller, M and Hellberg, Å and Olsson, M L}},
issn = {{1423-0410}},
language = {{eng}},
month = {{02}},
number = {{2}},
pages = {{185--197}},
publisher = {{Wiley-Blackwell}},
series = {{Vox Sanguinis}},
title = {{Thorough analysis of unorthodox ABO deletions called by the 1000 Genomes project}},
url = {{http://dx.doi.org/10.1111/vox.12613}},
doi = {{10.1111/vox.12613}},
volume = {{113}},
year = {{2018}},
}