1. Why are MeCP2 mutations always sporadic rather than hereditary? (2 marks)
The mutations of the MeCP2 gene are sporadic rather than hereditary because a female child with Rett syndrome will usually die at a very young age, however, if they also have a normal gene they may live longer but no family history has been found to be connected to RTT. The rare male who has RTT will die before or shortly after birth; therefore this disorder cannot be hereditary. Add notes from last weeks lecture
2. Contrast the genetic cause of Rett syndrome as compared to schizophrenia.
Explain your answer in general terms, address the relative involvement of genes and environment.
RTT is caused by the ...view middle of the document...
Therefore, if a male develops RTT he will be more severely affected due to the lack of a second X chromosome to compensate for the mutation. A male fetus affected by this mutation will usually result in a miscarriage. If a male is born, they will not have the typical clinical features of RTT and will usually die a few months after birth. Whereas females usually display symptoms a year after birth.
(b) Explain which figure in this paper best models the dosage of MeCP2 expression in female patients with Rett syndrome?
• (2 marks)
• Figures 2a and 2b best represent the presence or non-presence of MeCP2 in female patients with RTT. Figure 2a uses immunostaining to exhibit the absence of the receptor for MeCP2 in rats with RTT and the clear presence of MeCP2 in wild-type rats. It also shows the normal expression of GFAP in the astrocytes of wild-type and RTT rats. Figure 2b uses a western blot analysis to clearly exhibit the absence of the MeCP2 protein in RTT rats and the presence of MeCP2 in wild-type rats.
• However, figure 4a and 4b also show a beneficial model of the dosage of MeCP2 expression in females which exhibits the effect of combining the mutant and wild-type astrocytes. The researchers show that the wild-type ACM does not completely get rid of the effect of the mutant ACM on neural growth. The key representation in this model is that females with less MeCP2 expression can have a less severe form of RTT because they have two X chromosomes. I think the best model may be 4a. So just expand on that but the points on 2a & b are good too so I may be wrong..
• “This models the dosage of MeCP2 expression in female with less severe manifestation of Rett syndrome because the two chromosomes in female Rett patient with one normal X chromosome and a mutant X chromosome would be represented by wild type derived astrocytic conditioned media and the mutant astrocytic conditioned media, respectively.”
• 4. “There are several RTT mouse models, each of which contains different mutations in MeCP2.”
• Describe two ways in which a gene sequence can be disrupted and explain the consequences of this for protein translation. Do not investigate specific reported Rett syndrome mutations, describe general changes to genetic architecture.
• Gene sequences can be disrupted in a variety of ways; including frame shift mutations and base substitution mutations. A frame shift mutation occurs when bases in a gene sequences are added or deleted, this changes the reading frame in the mRNA that occurs after the mutation and alters the translated protein, resulting in a stop codon. A base substitution mutation is the trade of one base for another base, such a change produces a different codon and creates an alteration in the way the gene sequence is transcribed. This mutation created an alteration in the resulting protein. Gene mutations like this can have varying effects on health, depending on where they occur...