CHAPTER 24 – Evolution of Protein Molecules

The haemoglobin molecule is insensitive to replacements of most amino-acid residues on its surface, but extremely sensitive to even quite small alterations of internal non-polar contacts, especially those near the haems. Replacements at the contacts between α and β-subunits affect respiratory function.

Molecular Pathology of Human Haemoglobin

Isoelectric focusing of human hemoglobin: its application to screening, to the characterization of 70 variants, and to the study of modified fractions of normal hemoglobins

To search for a genetic marker for type 2 Gaucher's disease (acute neuronopathic form), we compared the nucleotide sequence of a cloned glucocerebrosidase gene from a patient with Gaucher's disease with a normal gene. We found only a single base substitution (T----C) in exon X. This mutation results in the substitution of proline for leucine in position number 444 and produces a new cleavage site for the NciI restriction endonuclease. We analyzed NciI enzymatic digests of genomic DNA from 20 patients with type 1, 5 with type 2, and 11 with type 3 Gaucher's disease, and 29 normal controls for a restriction-fragment-length polymorphism (RFLP). Four of 5 patients with type 2 disease and all 11 with type 3 disease had at least one allele with the mutation. Two of 5 patients with type 2 disease and 7 of 11 with type 3 were homozygous for this mutation. Only 4 of 20 patients with type 1 Gaucher's disease had the mutant allele and were heterozygous for it. None of the 29 normal controls had the mutant allele. The high frequency of this mutation (444leucine----proline) in patients with neuronopathic Gaucher's disease, detectable by the NciI RFLP, may be of value in the identification of patients who will have the neurologic sequelae of Gaucher's disease.

https://www.nejm.org/doi/pdf/10.1056/NEJM198703053161002?listPDF=true

A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease.

This chromatographic procedure uses DEAE-cellulose as ion exchanger and glycine-KCN-NaCl solutions as developers Blood samples from several adults and newborn infants with α, β, δ, or γ chain variants have been analysed The hemoglobins are eluted as compact and symmetrical zones, and the separation of many hemoglobin types is greatly improved The procedure is relatively fast, simple, and inexpensive

Separation of human hemoglobins by DEAE-cellulose chromatography using glycine-KCN-NaC1 developers.

Studies on the heterogeneity of hemoglobin. 13. Chromatography of various human and animal hemoglobin types on DEAE-Sephadex.

Hemoglobin C in Newborn Sheep and Goats: A Possible Explanation for its Function and Biosynthesis

/pdf/hemoglobin-c-in-newborn-sheep-and-goats-a-possible-2p6l8p6mfk.pdf

A.M. Dozy

Papers

Studies on the heterogeneity of hemoglobin. 13. Chromatography of various human and animal hemoglobin types on DEAE-Sephadex.

Hemoglobin C in Newborn Sheep and Goats : A Possible Explanation for its Function and Biosynthesis

Studies on the heterogeneity of hemoglobin. XIV. Chromatography of normal and abnormal human hemoglobin types on CM-Sephadex.

Studies on the heterogeneity of hemoglobin : IV. Chromatographic behavior of different human hemoglobins on anion-exchange cellulose (DEAE-cellulose)

Inhomogeneity of hemoglobin. VI. The minor hemoglobin components of cord blood.