The beautiful world of human haemoglobin (revisited)

Abstract

In this article I sought to tell two stories that were closely tied to each other. One was somewhat personal. It had to do with the course of my professional life, in Malta, the USA, then back to Malta. It involved family, a handful of mentors that shaped my career and many graduate students or trainees. They combined to link with the second objective of this article to recount our contributions to Human Haemoglobinopathy studies. Our research revealed the quantitative effects of genetic co-regulators on complex phenotypes. We assumed that mutations at two to three alleles acting among two to three (globin) loci could act to express a β globin gene variant at any level between as little as 5% or as much as 100% in heterozygotes. The same type of interaction could be seen in α globin and other molecules such as KLF1, the master regulator of Erythropoiesis, and perhaps others with a similar molecular model. The new health and academic professionals that we trained, the new resources in the hospital, the new laboratories and the new International Initiatives promise well for new discoveries to promote expedited diagnoses and new treatments of Rare Disease in general.