|MadSci Network: Genetics|
Down’s Syndrome is the most studied example of trisomy abnormality. Trisomy means that instead of having 2 (i.e. a pair) of homologous chromosomes, patients with trisomy have 3 (i.e. with an extra chromosome). Patients with Down’s Syndrome have 3 chromosome 21, hence the medical name Trisomy 21. The reason why Trisomy 21 is the most studied example of trisomy abnormality probably correlates to the fact that most of the other trisomy abnormalities are very severe and the frequency of live-born is relatively low, whereas trisomy 21 has a frequency of live-born, on average, of 1 in 600 (maybe implicating that chromosome 21 encodes for some relatively “non-vital” information?) There are 2 common causes of Trisomy 21:- 1. About 95% of it is caused by meiotic non-disjunction in which the pair of chromosome 21 fails to segregate at the FIRST meiotic division. Hence half the gametes have 2 copies of this chromosome, the other half have none. Notice that the latter are probably lethal, while the former, when fertilised by a normal gamete, will produce a trisomy zygote. It appears that such gametes are produced by the mother for the incidence of affected births is dependent on maternal age. 2. The remaining 5 % of it is caused by translocation of chromosome 21 to one of the other autosomes (commonly chromosome 14). Meiosis in this chromosome arrangement gives 1/3 of the gametes carrying the translocation together with chromosome 21, and fusion of such gamete with a normal gamete can generate a trisomy. As for your question, it is sure that people with Down’s do NOT all have the same level of mental retardation (in fact very few clinical conditions produce the same level of adverse effect). I have seen patients with Down’s who appear almost as intelligent as normal being compared with some cases having severe mental retardation, although most affected individuals do share certain clinical features, such as a characteristic flat facial appearance with slanting eyes, broad hands with short fingers and a single palmer crease across the hand. The reason for the wide range of severity of mental ability as seen in Down’s patients can probably be explained by the position on the chromosome breakage and recombination. As I have mentioned above, chromosome translocation is a cause of trisomy 21 and that as the position of breakage on chromosome 21 differs from case to case, and hence the length of chromosome 21 being “added” onto, say, chromosome 14 is different. So it is not difficult to speculate that this difference in breakage and recombination in translocation process may be a cause for the difference in severity of mental retardation for affected individuals. I hope I have answered your question:-) Joshua Chai Medical Student University of Cambridge United Kingdom
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