Genomic imprinting in diabetes

Abstract

Genomic imprinting refers to a class of transmissible genetic effects in which the expression of the phenotype in the offspring depends on the parental origin of the transmitted allele. The DNA from one parent may be epigenetically modified so that only a single allele of the imprinted gene is expressed in the offspring. Although imprinting has an important role in the regulation of growth and development through its role in regulating gene expression, its contribution to susceptibility to common complex disorders is not well understood. We summarize current views on the role of imprinting in diabetes and in particular chromosome 6q24-related transient neonatal diabetes mellitus, the best known example of an imprinted genetic disorder that leads to diabetes.

Figure 1

Summary of tiered genetic testing approach for 6q24-related transient neonatal diabetes mellitus (TNDM) as suggested by Temple and Mackay [39]. Adapted from and described in further detail in [39]; details of the method for determining the ratio of unmethylated to methylated DNA at 6q24 are in [34]. DMR, differentially methylated region; HIL, hypomethylation at imprinted loci; TNDM, transient neonatal diabetes mellitus; UPD, uniparental disomy. Paternal UPD is established after genotyping a panel of polymorphic markers on chromosome 6q in the parents and offspring and determining that the offspring carries only paternal alleles at each locus.