NIH Research Festival
Gaucher disease (GD) is an inherited autosomal recessive disorder characterized by mutations in GBA1 encoding the lysosomal enzyme glucocerebrosidase. Phenotypic heterogeneity among patients with different type of GD, even between sib pairs, has prompted the search for genetic modifiers or epigenetic modifications. One approach to investigating epigenetic variation has been to evaluate samples from twins. Mutational analysis of a monozygotic twin sisters revealed that both homozygous for the GBA1 mutation N188S, c.670C>T. Their clinical evaluation indicated that while both had GD, only one developed severe neurological symptoms. We performed epigenetic inactivation of genes by methylation of CpG islands using genomic DNA from each twin. Bisulfite treated DNAs were applied to an Illumina HumanMethylation450 BeadChip. Data were analyzed using GenomeStudio and GeneMANIA for network analysis. In the more affected twin, five methylated including CACNA1A and three demethylated genes were identified at CpG islands (P-value= 0.01-0.001) as well as two methylated genes from enhancer regions (P-value 0.05-0.01). RNA expression of the selected genes will be evaluated by real-time PCR. This study enhances our understanding of the complexity in Gaucher disease, identifies possible cause of phenotypic variation. Additionally the data confirm the value of epigenetic events on disease cause as well as phenotypic variation basis among monogenic and multifactorial diseases.
Scientific Focus Area: Genetics and Genomics
This page was last updated on Friday, March 26, 2021