@article{discovery1412371,
           month = {January},
          number = {1},
         journal = {Ann Hum Genet},
           title = {Dominant PRPF31 Mutations Are Hypostatic to a Recessive CNOT3 Polymorphism in Retinitis Pigmentosa: A Novel Phenomenon of "Linked Trans-Acting Epistasis"},
            year = {2014},
            note = {?{\copyright} 2013 The Authors.
Annals of Human Genetics published by John Wiley \& Sons Ltd/University College London.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution
in any medium, provided the original work is properly cited, the use is non-commercial and no modification or adaptations are made.},
          volume = {78},
           pages = {62--71},
        keywords = {CNOT3, PRPF31, epistasis, retinitis pigmentosa},
        abstract = {Mutations in PRPF31 are responsible for autosomal dominant retinitis pigmentosa (adRP, RP11 form) and affected families show nonpenetrance. Differential expression of the wildtype PRPF31 allele is responsible for this phenomenon: coinheritance of a mutation and a higher expressing wildtype allele provide protection against development of disease. It has been suggested that a major modulating factor lies in close proximity to the wildtype PRPF31 gene on Chromosome 19, implying that a cis-acting factor directly alters PRPF31 expression. Variable expression of CNOT3 is one determinant of PRPF31 expression. This study explored the relationship between CNOT3 (a trans-acting factor) and its paradoxical cis-acting nature in relation to RP11. Linkage analysis on Chromosome 19 was performed in mutation-carrying families, and the inheritance of the wildtype PRPF31 allele in symptomatic-asymptomatic sibships was assessed-confirming that differential inheritance of wildtype chromosome 19q13 determines the clinical phenotype (P {\ensuremath{<}} 2.6 {$\times$} 10(-7) ). A theoretical model was constructed that explains the apparent conflict between the linkage data and the recent demonstration that a trans-acting factor (CNOT3) is a major nonpenetrance factor: we propose that this apparently cis-acting effect arises due to the intimate linkage of CNOT3 and PRPF31 on Chromosome 19q13-a novel mechanism that we have termed "linked trans-acting epistasis."},
          author = {Rose, AM and Shah, AZ and Venturini, G and Rivolta, C and Rose, GE and Bhattacharya, SS},
             url = {http://dx.doi.org/10.1111/ahg.12042}
}