As a result of international collaboration between research centers from Poland, Hungary and Japan, genetic tests have been performed and among them study of genetic variation of the ABCB6 gene, including samples from genetic collection POPULOUS deposited at the BioBank Lab. Polish part of the research has been conducted using inter alia robotic part of the laboratory, in which the main role played JANUS – pipetting liquids automated station using scripts created at the BioBank Lab. Research results have been published in PLoS One (IF = 3,53) in OPEN ACCESS status. Enjoy your reading.

 

Screening the Expression of ABCB6 in Erythrocytes Reveals an Unexpectedly High Frequency of Lan Mutations in Healthy Individuals

 

Magdalena Koszarska1, Nora Kucsma2, Katalin Kiss2, Gyorgy Varady2, Melinda Gera2, Geza Antalffy2, Hajnalka Andrikovics1, Attila Tordai1, Maciej Studzian4, Dominik Strapagiel5, Lukasz Pulaski4, Yoshihiko Tani6, Balazs Sarkadi1,2,3, Gergely Szakacs2

 

1 Hungarian National Blood Transfusion Service, Budapest, Hungary,

 

2 Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary,

 

3 Molecular Biophysics Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary,

 

4 Department of Molecular Biophysics, University of Łódź, Łódź, Poland,

 

5 Biobank Lab, Department of Molecular Biophysics, University of Łódź, Łódź, Poland,

 

6 Japanese Red Cross Kinki Block Blood Center, Osaka, Japan

 

Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC) surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals. Sequencing of the entire coding region of the ABCB6 gene in low RBC ABCB6 expressors identified a new allele (IVS9+1G>A, affecting a putative splice site at the boundary of exon 9) and two nonsynonymous SNPs listed in the SNP database (R192Q (rs150221689) and G588 S (rs145526996)). The R192Q mutation showed co-segregation with reduced RBC ABCB6 expression in a family, and we found the G588 S mutation in a compound heterozygous individual with undetectable ABCB6 expression, suggesting that both mutations result in weak or no expression of ABCB6 on RBCs. Analysis of the intracellular expression pattern in HeLa cells by confocal microscopy indicated that these mutations do not compromise overall expression or the endolysosomal localization of ABCB6. Genotyping of two large cohorts, containing 235 and 1039 unrelated volunteers, confirmed the high allele frequency of Lan-mutations. Our results suggest that genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought.

 

The research was funded by: POIG grant 01.01.02-10-005/08 TESTOPLEK

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