Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.

Isoelectric focusing, cellulose acetate electrophoresis, and carboxymethylcellulose chromatography in the presence of Nonidet P-40 allow the separation of pure gamma chains into two fractions. Amino acid analysis of their cyanogen bromide fragment 3 (gamma CB3) identifies these fractions as the separated G gamma (Gly-136) and A gamma (Ala-136) globin chains. Fingerprint and amino acid analyses of the gamma Tp9 tryptic peptide from the purified A gamma and G gamma fractions from two different patients demonstrate that the commonly occurring gamma Sardinia variant (gamma 75 isoleucine leads to threonine), also known as T gamma chain, has alanine in position 136. From this analysis we suggest that the T gamma gene is an allele of the A gamma locus (A gamma Sardinia) rather than a third gamma locus.

Three Negro kindreds with hereditary persistence of fetal hemoglobin (HPFH) alone and in combination with various other hemoglobin abnormalities including beta thalassemia are presented. Among 11 offspring of two women heterozygous for both HPFH and the delta chain mutation Hb B2, five inherited the HPFH gene and six inherited the Hb B2 gene. In another kindred, a man inferred to be heterozygous for both HPFH and Hb C had six children; three offsprivg obtained the Hb C gene and three the HPFH gene. Similarly, a woman heterozygous for both Hb S and HPFH transmitted the Hb S gene to one of her two children and the HPFH gene to the other. Thus among 19 offspring, no crossovers between the HPFH locus or the Hb delta-beta locus were observed. These and earlier data are compatible with deletion of the Hb beta and delta loci as the primary event to explain the genetic origin of HPFH. Genetic considerations indicate that the finding of a single person with a hematologically normal phenotype among offspring of heterozygotes for both the African type of HPFH and a Hb beta or Hb delta structural abnormality would invalidate the deletion model.

Two dimensional gel analysis of skeletal muscles from normal pigs and from pigs which were homozygous for halothane sensitivity showed no obvious differences in the patterns of spots attributed to the major contractile proteins and glycolytic enzymes. In muscle from a sensitive pig which died of heat shock under anaesthesia there was a selective loss of glyceraldehyde-3-phosphate dehydrogenase and aldolase, presumably owing to proteolytic activity. The progressive loss of these enzymes under anaesthesia could contribute to the mechanism of heat production by diverting fructose 1,6 diphosphate into a futile cycle.

Malignant hyperthermia occurs in man and pigs as a hereditary disorder notably as a complication of halothane-induced anaesthesia. It involves an abnormality in the metabolism of Ca2+. A search was made for abnormalities of calcium-binding proteins. Troponin C from normal pig muscle was found to differ in 2 of 159 amino acids from rabbit Tn C and 3 from man. No differences between normal and abnormal pig muscle were found. Two-dimensional electrophoresis of red cell calmodulin from normal and abnormal pigs also failed to demonstrate a difference.