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Biomedical subjects

John M Old

Publications and source records attributed to John M Old.

6 recordsLinked to original sources
PubMed2006

Hb Bart's in cord blood: an accurate indicator of alpha-thalassemia.

We quantified Hb Bart's (gamma4) levels by high performance liquid chromatography (HPLC) in 103 fresh cord blood samples from Homerton Hospital, East London, UK. The alpha-globin gene arrangement was determined by Southern blot hybridization and genomic sequence analysis of the alpha-globin genes. The cord blood Hb Bart's levels ranged from 0.5 to 11.9% of total hemoglobin (Hb) and were arranged into three categories: i) levels below 1.5%; ii) levels between 1.5 and 5.7%; iii) levels above 6.1%. These corresponded to a normal alpha-globin genotype, a single deleted/inactivated alpha-globin gene and two deleted/inactivated alpha-globin genes, respectively. The study identified the 3.7 kb and 20.5 kb alpha-thalassemia (thal) deletions, three non deletional alpha-thal mutations and a novel alpha-globin gene rearrangement. Hb Bart's screening of fresh umbilical cord blood is an effective method to evaluate globin chain imbalance. This strategy could be utilized to screen populations for the incidence of alpha-thal and also to identify rare or new molecular lesions that reduce alpha-globin gene expression.

Chromatography, High Pressure Liquid↗
PubMed2003

The molecular basis for the thalassaemias in Sri Lanka.

The beta-globin gene mutations and the alpha-globin genes of 620 patients with the phenotype of severe to moderate thalassaemia from seven centres in Sri Lanka were analysed. Twenty-four beta-globin gene mutations were identified, three accounting for 84.5% of the 1240 alleles studied: IVSI-5 (G-->C) 56.2%; IVSI-1 (G-->A) 15.2%; and haemoglobin E (codon (CD)26 GAG-->GAA) 13.1%. Three new mutations were found; a 13-bp deletion removing the last nucleotide in CD6 to CD10 inclusively, IVSI-129 (A-->C) in the consensus splice site, and a frame shift, CD55 (-A). The allele frequency of alpha+ thalassaemia was 6.5% and 1.1% for -alpha3.7 and -alpha4.2 deletions respectively. Non-deletion alpha-thalassaemia was not observed. Triplicate or quadruplicate alpha-globin genes were unusually common. In 1.5% of cases it was impossible to identify beta-thalassaemia alleles, but in Kurunegala detailed family studies led to an explanation for the severe thalassaemia phenotype in every case, including a previously unreported instance of homozygosity for a quadruplicated alpha-globin gene together with beta-thalassaemia trait. These findings have implications for the control of thalassaemia in high-frequency populations with complex ethnic histories.

Blotting, Southern↗