In huntingtin gene, 67 exons regions are available. In which exon does the disease causing variable number of CAG repeats occur?
The disease-causing repeat is in exon 1. The pathological effect is due to the cag coding for polyglutamine (so, it is not and cag repeat, it's an in-frame cag repeat). Polyglutamine is thought to cause aggregation, but context of the protein, i.e., the surrounding amino acids are relevant (see link). The huntingtin repeat has to exceed about 35 repeats to result in disease, so it is quite long.
http://genesdev.cshlp.org/content/15/8/925.full
The expansion of CAGs are happening in the exon 1. Moreover, the severity of the disease depends on the number of repeats but because there is a great variability in the phenotypes shown by the same number of repeats, it is believed that other genes are involved in the severity of the disease. Moreover, there are several models in which only the first exon followed by different CAG repeats is expressed and others expressing full-length HTT with different CAG repeats. The first model (only the first exon) shows the strongest phenotype compared to the full-lenght.
the features discussed by Carlo and Gerard apply similarly to the other CAG repeat expansion diseases. In the healthy population these repeats are of variable length (9-40).
adding to what have been said by the last three experts, in general, CAG repeat variation happens in regions with a minimal number of CAG repeats. The molecular mechanism behind the variation is slippage during DNA replication, which happens in regions with simple repeats, resulting in reduction or expansion of these short tandem repeats. The same mechanism is responsible for causing other trinucleotide repeat variation disorders. The reason that trinucleotide repeat disorders are seen more often than other types of simple nucleotide repeats (e.g. di-nucleotides or tetra-nuecleotides) is that trinucletoide repeat variation maintains the correct reading frame, thus it is less detrimental than others (which might be lethal).
thanks to all, in case of other CAG expansion disease such HDL2,SCA,SBMA(polyq diseases)...etc, disease causing repeats variation occurs in exon 1 region like HD or it may vary?
Different genes would have the CAG repeats located in different locations/exons
Thanks for considered my request and supported me by answering my question.....I completed my academic master's project.......I designed a small tool for Huntington disease prediction. I need Huntington dataset containing age and age of onset to proceed validation or modelling using fuzzy neurons.....could you help me with dataset or at best ,where can i get dataset.
Thanks and Regards,
Aslam.
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