Identification of an uncommon haptoglobin type using DNA and protein analysis

The inherited variations in haptoglobin phenotypes are attributed to the homozygous and heterozygous combinations of three common autosomal alleles:HP ^* 1F,HP ^* 1S andHP ^* 2.HP ^* 1F andHP ^* 1S encode polypeptides that differ by two amino acids at positions 51 and 53. The formation ofHP ^* 2 is postulated to have resulted from a breakage and subsequent reunion event at non-homologous positions of twoHP ^* 1 alleles. The most common form ofHP ^* 2 isHP ^* 2FS in which the 5 end ofHP ^* 2 resemblesHP ^* 1F and the 3 end resemblesHP ^* 1S. Homologous crossing over betweenHP ^* 2 and either anHP ^* 1F orHP ^* 1S allele inHP ^* 2/HP ^* 1 heterozygotes can change the usual type ofHP ^* 2 to three other forms:HP ^* 2SS,HP ^* 2FF orHP ^* 2SF. We describe a nuclear family in which the uncommon genotypeHP ^* 2SS in one parent caused initial confusion in assigning genotypes to the rest of the nuclear family. The data demonstrate the need for a cautious approach when deducing haptoglobin genotypes from molecular analysis alone.