Identification and Monitoring of Nucleotide Repeat Expansions Using Southern Blotting in Models of Motor Neuron Disease and Frontotemporal Dementia.

Repeat expansion diseases, including fragile X syndrome, Huntington's disease, and -related motor neuron disease and frontotemporal dementia, are a group of disorders associated with polymorphic expansions of tandem repeat nucleotide sequences. These expansions are highly repetitive and often hundreds to thousands of repeats in length, making accurate identification and determination of repeat length via PCR or sequencing challenging. Here we describe a protocol for monitoring repeat length in models carrying 1,000 repeat -related dipeptide repeat transgenes using Southern blotting.

Modeling -Related Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in .

An intronic hexanucleotide (GGGGCC) expansion in the gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In the decade following its discovery, much progress has been made in enhancing our understanding of how it precipitates disease. Both loss of function caused by reduced transcript levels, and gain of function mechanisms, triggered by the production of repetitive sense and antisense RNA and dipeptide repeat proteins, are thought to contribute to the toxicity.