What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration
Article first published online: 12 NOV 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 4, pages 325–333, April 2012
How to Cite
Ketelaar, M., Hofstra, R. and Hayden, M. (2012), What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration. Clinical Genetics, 81: 325–333. doi: 10.1111/j.1399-0004.2011.01795.x
- Issue published online: 14 MAR 2012
- Article first published online: 12 NOV 2011
- Accepted manuscript online: 7 OCT 2011 03:32PM EST
- Received 26 June 2011, revised and accepted for publication 4 October 2011
- disease discordance;
- monozygotic twins;
Ketelaar ME, Hofstra RMW, Hayden MR. What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration.
As monozygotic (MZ) twins are believed to be genetically identical, discordance for disease phenotype between MZ twins has been used in genetic research to understand the contribution of genetic vs environmental factors in disease development. However, recent studies show that MZ twins can differ both genetically and epigenetically. Screening MZ twins for genetic and/or epigenetic differences could be a useful and novel approach to identify modifying factors influencing phenotypic expression of disease. MZ twins that are phenotypically discordant for monogenic diseases are of special interest. Such occurrences have been described for Huntington's disease, spinocerebellar ataxias, as well as for familial forms of Alzheimer's disease. By comparing MZ twins that are phenotypically discordant, crucial factors influencing the phenotypic expression of the disease could be identified, which may be of relevance for understanding disease pathogenesis and variability in disease phenotype. Overall, understanding the crucial factors in development of a neurodegenerative disorder will have relevance for predictive testing, preventive treatment and could help to identify novel therapeutic targets.