Tuesday, 20 March 2012

The Hunt For The Genetic Offender Responsible For Down Syndrome

The Hunt For The Genetic Offender Responsible For Down Syndrome

Down Syndrome (DS) is a chromosomal disorder and occurs in approximately 1 in 750 live births. (Lana-Elola, E et al. 2011) It is caused by the trisomy, an extra copy, of the human chromosome 21 (HSA21) and so there are three chromosomes instead of the usual pair of two. (Amano, K. et al 2004) Because the cells in chromosome 21 are trisomic, Down syndrome is also known as trisomy 21. (Reece, J et al. 2011) It causes numerous phenotypes such as distinguishing facial fatures, cardiac defects and mental retardation, characteristics of which vary in severity depending on the individual. (Pennington, B.F et al. 2003)

Figure 1: Karotype from a female with Down Syndrome

Recent Down Syndrome research has been focused on identifying the specific genes and molecular mechanisms responsible for the DS phenotypes and the general hypothesis has assumed that the over-expression of a number of these dosage-sensitive genes present in the HSA21 is the cause. (Lana-Elola, E et al. 2011) However, an absolute confirmation of the hypothesis has yet to be given and this has lead to researchers at the RIKEN Brain Science Institute to investigate the gene(s) causing the abnormalities of DS through the use of DS mouse models. (Amano, K. et al 2004)

The study involved the observation of the mouse chromosome 16 (MMU16), essentially a model of the HSA21 of humans. (Amano, K. et al 2004) The MMU16 in the brains of normal mice were compared with that of the DS mouse models, called Ts1Cje, that expressed abnormalities associated with learning and behaviour (similar to that of DS). (Amano, K et al. 2004)

The results showed that most of the trisomic genes were approximately 1.5-fold over-expression while the majority of expression levels of genes not located in the MMU16 were found to be the same in both the Ts1Cje and the normal mice. (Amano, K et al, 2004) Therefore, it can be seen that the results further supported the general hypothesis that the DS phenotypes are caused by the increase of genes present in the trisomic region of HSA21. (Amano, K et al. 2004)

The outcomes from this particular study and other studies have exemplified that dosage-sensitivity could be made to occur in mice resulting in characteristics analogous to DS in humans. (Lana-Elola, E et al. 2011) Furthermore, the studies have also been able to locate dosage-sensitive genes which have indicated that a substantial amount of DS phenotypes are more probable to be triggered by the increased expression of more than one HSA21 gene rather than a single gene. (Lana-Elola, E et al. 2011)

The understanding of the underlying factors involved in the pathology of Down Syndrome has moved forward substantially and looks very promising. However, further research is required for full comprehension, specifically in order to determine the dosage-sensitive genes accountable for Down Syndrome so that this knowledge can be applied in the development of more effective therapy.  

Phillip Lee, 42929718

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