Parkinson phenotype

Once data from thousands of different sequences derived from thousands of different tissues has been compiled, bioinformatic analysis of the data allows us to identify genes that show restricted patterns of expression, assisting in both annotation of function, and association with phenotype. This analysis can be extended to look for novel markers or targets, by analyzing those novel sequences that are co-expressed with known markers or targets. This has been applied to a number of diseases already, such as prostate cancer and Parkinson s disease [120, 164]. 

Phenotypically, different neurodegenerative disorders, including AD, Parkinson disease, and prion diseases (transmissible spongiform encephalopathies), are... 

Van Swieten, J.C., Rosso, S.M., van Herpen, E., Kamphorst, W., Ravid, R., Heutink, P. (2004) Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17. Dement. Geriatr. Cogn. Disord., 17, 261-264. 

Cory-Slechta DA, Thiruchelvam MT, Richfield EK, Barlow BK, Brooks Al (2005) Developmental pesticide exposures and the Parkinson s disease phenotype. Birth Defects Res A Clin Mol Teratol, 73 136-139. 

The last decade has provided new molecular and genetic tools for the analysis of changes in the dopamine turnover, particularly in the generation of strains of knockout mice that are deficient in various aspects of dopamine neurone development, in the cellular machinery for dopamine neurotransmission, or in other genes associated with parkinsonism in man. As several good recent reviews are available (Jankowsky et al., 2002 Eells, 2003), the present account will focus on the behavioral phenotypes associated with genetic manipulation of dopamine systems of the forebrain. 

Sedelis M, Schwarting RK, Huston JP (2001) Behavioral phenotyping of the MPTP mouse model of Parkinson s disease. Behav Brain Res 725 109-125. 

Higashi S, Moore DJ, Colebrooke RE, Biskup S, Dawson VL, Arai H, Dawson TM, Emson PC (2007b) Expression and localization of Parkinson s disease-associated leucine-rich repeat kinase 2 in the mouse brain. J Neurochem 100 368-381 Higgins GA, Jacobsen H (2003) Transgenic mouse models of Alzheimer s disease phenotype and application. Behav Pharmacol 14 419—438... 

Gan-Or Z, Giladi N, Rozovski U, Shifrin C, Rosner S, Gurevich T, Bar-Shira A, Orr-Urtreger A (2008) Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurology 70 2277-2283... 

Hiller A, Hagenah JM, Djarmati A, Hedrich K, Reetz K, Schneider-Gold C, Kress W, Munchau A, Klein C (2007) Phenotypic spectrum of PlNKl-associated parkinsonism in 15 mutation carriers from 1 family. Mov Disord 22 145-147... 

PSP is the second most common cause of Parkinsonism typified by early gait instability and difficulty with vertical eye movement. PSP is characterized by neurofibrillary tangles composed almost entirely of sdaight filaments of four repeats of Tau protein. Although most cases of PSP appear to be sporadic, genetic diatheses have been implicated. De Yebenes described a pattern of inheritance consistent with a Mende-lian autosomal dominant disorder (De Yebenes et al., 1995). Difficulty recognizing the variable phenotypic expression of PSP may be one reason fewer familial cases have been identified than expected (Rojo et al., 1999). The HI haplotype of the Tau gene has also been found to have association with increased risk for PSP, as it has been for PD (Conrad et al.. 

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