Gene mapping and chromosome 21: history and methodology.

Abstract

The early descriptions of mongolism were, of course, clinical and involved characteristics about the genetics of which we still know next to nothing, bodily form and mental characteristics, where the combination of genes and environment baffles the most sophisticated analysis. The next stage was the description of physiological functions and then of enzyme levels. When it came to the enzymes, the genetical basis was clearer, in a general way, in that protein structure had been shown to be directly under the control of DNA, but the gap between that fact and attributing any functional protein disturbance directly to a particular gene is very large. Many quantitative abnormalities in enzyme and protein levels were indeed reported, but this is hardly surprising in a condition such as mongolism where abnormality is so all-pervasive that secondary effects must obviously be more frequent than primary ones. Investigations of qualitative rather than quantitative differences are more characteristic of conventional linkage analysis, and these were foreshadowed in 1927 when Orel published family data that included the ABO blood groups. This was very far from being presented in linkage terms since the concept was then unknown in medicine.