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Genetic variation of the whole ICAM4 gene in Caucasians and African Americans

Authors

  • Kshitij Srivastava,

    1. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
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  • Noorah Salman Almarry,

    1. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    2. Department of Biochemistry & Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC
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  • Willy A. Flegel

    Corresponding author
    1. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    • Address reprint requests to: Willy A. Flegel, MD, Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892; e-mail: bill.flegel@nih.gov.

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  • This research was supported by the Intramural Research Program of the NIH Clinical Center.
  • The views expressed do not necessarily represent the view of the National Institutes of Health, the Department of Health and Human Services, or the U.S. Federal Government.

Abstract

Background

Landsteiner-Wiener (LW) is the human blood group system Number 16, which comprises two antithetical antigens, LWa and LWb and the high-prevalence antigen LWab. LW is encoded by the intracellular adhesion molecule 4 (ICAM4) gene. The ICAM4 protein is part of the Rhesus complex in the red cell membrane and is involved in cell–cell adhesion.

Study Design and Methods

We developed a method to sequence the whole 1.9-kb ICAM4 gene from genomic DNA in one amplicon. We determined the nucleotide sequence of Exons 1 to 3, the two introns, and 402-bp 5′-untranslated region (UTR) and 347-bp 3′-UTR in 97 Caucasian and 91 African American individuals.

Results

Seven variant ICAM4 alleles were found, distinct from the wild-type ICAM4 allele (GenBank KF712272), known as LW*05 and encoding LWa. An effect of the LWa/LWb amino acid substitution on the protein structure was predicted by two of the three computational modeling programs used.

Conclusions

We describe a practical approach for sequencing and determining the ICAM4 alleles using genomic DNA. LW*05 is the ancestral allele, which had also been observed in a Neanderthal sample. All seven variant alleles are immediate derivatives of the prevalent LW*05 and caused by one single-nucleotide polymorphism (SNP) in each allele. Our data were consistent with the NHLBI GO Exome Sequencing Project (ESP) and the dbSNP databases, as all SNPs had been observed previously. Our study has the advantage over the other databases in that it adds haplotype (allele) information for the ICAM4 gene, clinically relevant in the field of transfusion medicine.

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