title: Genetic variation of the whole ICAM4 gene in Caucasians and African Americans.
abstract: BACKGROUND
  Landsteiner-Wiener (LW) is the human blood group system Number 16, which comprises two antithetical antigens, LW(a) and LW(b) and the high-prevalence antigen LW(ab) . 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.
  
  
  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 LW(a) . An effect of the LW(a) /LW(b) 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.
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Srivastava
authors.forename: Noorah Salman
authors.initials: NS
authors.lastname: Almarry
authors.forename: Willy A
authors.initials: WA
authors.lastname: Flegel
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005091:Exons / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; C095100:ICAM4 protein, human