Opis

• Tytuł:
  Screening the Expression of ABCB6 in Erythrocytes Reveals an Unexpectedly High Frequency of Lan Mutations in Healthy Individuals
• Twórca:
  Koszarska, Magdalena;
  Kucsma, Nora;
  Kiss, Katalin;
  Varady, Gyorgy;
  Gera, Melinda;
  Antalffy, Geza;
  Andrikovics, Hajnalka;
  Tordai, Attila;
  Studzian, Maciej;
  Strapagiel, Dominik;
  Pulaski, Lukasz;
  Tani, Yoshihiko;
  Sarkadi, Balazs;
  Szakacs, Gergely
• Współtwórca:
  Hungarian National Blood Transfusion Service;
  Hungarian Academy of Sciences, Institute of Enzymology;
  Semmelweis University;
  University of Lodz, Department of Molecular Biophysics;
  Japanese Red Cross Kinki Block Blood Center;
  szakacs.gergely@ttk.mta.hu
• Opis:
  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.;
  This work was supported by the Lendulet Program of the Hungarian Academy of Sciences (GS), OTKA 83533 and by the Polish POIG grant 01.01.02-10-005/08 TESTOPLEK, supported by the EU through the European Regional Development Fund. Hajnalka Andrikovics is a recipient of the Janos Bolyai Research Scholarship from the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Camilo Toro and Dr. William Gahl of the NIH Undiagnosed Diseases Program for an affected patient specimen; that work was supported by the Intramural Research Program of the National Human Genome Research Institute and the Office of the Director of the NIH. We thank Lionel Arnaud (National Institute of Blood Transfusion (INTS), Paris, France) for helpful discussions.
• Dostępność obiektu:
  Dostęp otwarty
• Prawa:
  Uznanie autorstwa 3.0 Polska;
  http://creativecommons.org/licenses/by/3.0/pl
• Data:
  2016.04.12;
  2014
• Typ:
  Article
• Język:
  angielski
• Format:
  application/pdf
• Wydawca:
  PLOS
• Relacja:
  PLOS One;10;
  9
• Identyfikator:
  1932-6203;
  http://hdl.handle.net/11089/17783 ;
  10.1371/journal.pone.0111590
• Dostawca danych:
  Repozytorium Uniwersytetu Łódzkiego
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