C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease.
Bottom Line: We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk.However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls.Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP.
Affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Biomedical Research building, 1501 NW 10th Ave, Miami, FL, 33136, USA.Show MeSH
Related in: MedlinePlus
Mentions: We performed Southern blot analysis to determine whether the clinically affected individuals with>20 RCs are heterozygous or homozygous carriers of two intermediate RC alleles, as therepeat-primed PCR for Patient 1 (P1) indicated two possible alleles with intermediate repeat copies(Fig. 5B). All but two of the intermediate RC carriers ofthe original dataset were shown to be heterozygous for the intermediate allele and a low copy numberallele (data not shown). The two other samples (P1; P9, Fig. 6) were further analysed with additional control samples (see below). For Southern blotanalysis of the NINDS intermediate samples, we obtained additional DNA from cultured cells. However,the DNA quality was insufficient to obtain a distinct band on Southern blot after multipleattempts.
Affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Biomedical Research building, 1501 NW 10th Ave, Miami, FL, 33136, USA.