Finally, parent-of-origin effects have been reported in human phenotypes associated with mutations in RB1. These include parental effects on the differential penetrance and age of onset in RB, and an excess of first somatic mutations on paternal alleles in sporadic osteosarcoma (Toguchida et al., 1989; Klutz et al., 2002; Richter et al., 2003; Schuler et al., 2005). Here, RB1 is linked to retinoblastoma.