Expansion of a GGGGCC hexanucleotide repeat sequence in the non-coding region of human chromosome 9 open reading frame 72 or C9orf72 (also known as ALSFTD, FTDALS; Gene ID 203228) is the most common genetic abnormality in familial and sporadic frontotemporal dementia (FTD) and motor neuron disease (MND), with amyotrophic lateral sclerosis (ALS) as the most frequent form. The number of hexanucleotide repeats in the normal population ranges from 2 to 24, whereas up to several thousand repeats (700 - 4,400 repeats) are found in the pathologically expanded allele. Unconventional repeat-associated non-ATG-initiated translation (RANT) of the GGGGCC repeats in the three alternate reading frames generates three polypeptides, each composed of repeating units of two amino acids (dipeptide repeats, DPRs), glycine-alanine (GA), glycine-proline (GP), and glycine-arginine (GR), respectively. These DPR proteins form inclusions particularly in the cerebellar cortex, hippocampus and cerebral neocortex. These inclusions are also immunoreactive for markers of the ubiquitin proteasome system (UPS), including ubiquitin, ubiquilins, and p62, but is distinct from inclusions containing TDP-43 that is also found in FTLD-TDP (frontotemporal lobar degeneration with TDP-43 pathology) and ALS cases. Antibodies against poly-GA, poly-GP, and poly-GR sequence are useful for characterizing the neuroanatomical distribution and clinico-pathological association of DPR pathology with C9ORF72 mutations.
Synonyms: C9ORF72/C9RANT (poly-GA), Protein C9orf72
Application: Western Blotting Analysis: A representative lot detected recombinant GST fusion with 15 GA repeats (Mackenzie, I.R., et al. (2013). Acta Neuropahol. 126(6):859-879).Immunohistochemistry Analysis: A representative lot detected C9ORF72/C9RANT with 15 GA repeats in cerebellum from a C9ORF72 mutation case (Mackenzie, I.R., et al. (2013). Acta Neuropahol. 126(6):859-879).
Other Notes: Concentration: Please refer to lot specific datasheet.