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: HP1F, HP1S and HP2. HP1F and HP1S encode polypeptides that differ by two amino acids at positions 51 and 53. The formation of HP2 is postulated to have resulted from a breakage and subsequent reunion event at non-homologous positions of two HP1 alleles. The most common form of HP2 is HP2FS in which the 5' end of HP2 resembles HP1F and the 3' end resembles HP1S. Homologous crossing over between HP2 and either an HP1F or HP1S allele in HP2/HP1 heterozygotes can change the usual type of HP2 to three other forms: HP2SS, HP2FF or HP2SF. We describe a nuclear family in which the uncommon genotype HP2SS is 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.