GENETIC VARIATION IN THE SHEEP RED BLOOD CELL

1. There are 7 well-established red-cell antigen (blood group) loci. The R-O system has 3 phenotypes, R, O and i, identified by the ‘naturally occurring’ antibodies, anti-R and anti-O. The R and O substances are also present in soluble form in some body secretions. The expression of R and O is controlled by a dominant gene I, epistatic in effect, at an independent locus from that of R. The systems, A, C, M-L, B, D and X-2 are identified by means of ‘immune-type’ antibodies, and several of the loci have multiple alleles. An isoenzymic form of serum alkaline phosphatase is associated with the R-O system. The frequency for the genes at the various loci has been determined in a limited number of breeds. 2. Some sheep red cells have high K+ and low Na+ concentrations (HK type, or Key), others have low K+ and high Na⁺ concentrations (LK type or Kea). Two other rare forms exist; Key type which is HK but with lower than normal K+ values, and Kep type which has approximately equal Na⁺ and K⁺ concentrations. The red cells of foetuses and newborn lambs have high K+ levels irrespective of their potassium genotype. HK cells have 3–4 times greater (Na+-K+)-activated ATPase activity, a 3–4 times increased rate of active K+ transport and a larger number of ouabain-binding sites than LK cells. Antigen M is present on homozygous HK and heterozygous LK red cells, and antigen L is present on homozygous and heterozygous LK red cells. Sensitization of LK cells with anti-L stimulates active K+ transport and ATPase activity and exposes a larger number of ouabain-binding sites in these cells. Anti-M has no effect. The red cells of newborn lambs only show weak L and M antigen activity. It is postulated that L antigen inhibits cation transport in LK cells by masking the pump sites on the membrane. Immature red cells in LK-type sheep have a high rate of active K+ transport and yet have L antigen present. No satisfactory explanation for this has yet been advanced. There is no conclusive evidence that the potassium types have any significance from the point of view of adaptation or sheep breeding. The potassium-gene frequencies are known for a large number of breeds. 3. Two allelic genes, Hb⁴ and Hb^B control 3 haemoglobin phenotypes, A, AB, and B. Foetal haemoglobin (HbF) is present in foetuses and newborn lambs. Sheep with HbA also synthesize small amounts of another haemoglobin (HbC) and under conditions of severe anaemia, synthesis of HbC takes over from that of HbA. No change in HbB is observed in anaemia. A rare haemoglobin (HbD) has been found in 3 Yugoslavian sheep. Hbs A, B, C and F differ in their physicochemical properties; they share the same alpha chains but their non-alpha chains differ in a number of amino acids. HbD differs from HbA in one amino acid in the alpha chain. Certain genetic aspects are discussed. There is some evidence that sheep with HbA are less fertile than those with HbB. The gene frequencies for Hb are known for a large number of breeds. 4. Two isoenzymic forms of carbonic anhydrase are found in red-cell lysates and these are controlled by a pair of allelic autosomal genes, producing 3 phenotypes, CAF, CAFS and CAS. Only a few breeds have been studied but CA^F is apparently quite rare. 5. An unidentified protein, designated ‘X’ is present in electrophoretic separations of haemolysates from some sheep. Its presence is dominant to its absence. Polymorphism at this locus is present in all breeds so far studied. 6. A deficiency of reduced glutathione (GSH) in red cells is found in some sheep and is inherited as an autosomal recessive disorder. Sheep with this deficiency have lower red-cell K+ and Na^f concentrations than normal and it is suggested that the HK GSH-deficient sheep may be Ked type sheep. This deficiency has so far only been found with certainty in one breed of sheep. 7. In sheep twin chimeras, admixture of red-cell antigens, haemoglobin and ‘X’ protein types has been found. Various aspects of chimerism, which occurs only rarely in sheep, are discussed. 8. The significance of the genetic variation is discussed in the light of the physiology and immunology of the red cell and of the sheep itself.