Abstract
Proteomic-based approaches, which examine expressed proteins in tissues or cells, have great potential in the elucidation of biological defects in heterogeneous neurodevelopmental disorders such as autism. In this approach, tissue or cellular proteins from control and affected subjects are separated on two-dimensional (2-D) polyacrylamide gel electrophoresis, and those proteins that show marked changes in the concentration between control and affected subjects are identified by mass spectroscopy. This method has been successfully applied in the elucidation of the molecular biological defect in classic late-infantile neuronal ceroid lipofuscinosis (Sleat et al., 1997). Unlike the classical methods of genome-wide screening for chromosomal localization followed by positional cloning, the proteomic approach requires limited number of tissue samples and the study can be completed in a relatively short time. Currently, these methods are available for relatively abundant proteins and generally are not applicable for hydrophobic proteins because 2-D gel electrophoresis is not very effective in the analysis of hydrophobic proteins. The genetic defect results in either total loss of proteins or changes in molecular weight and/or isoelectric point will be detectable by the proteomic method. Because autism is a neurogenetic disorder, brain is the tissue of choice for proteomic study. For an oligogenic disorder such as autism, at least some of the aberrant (genes) proteins may be identified by this technology.
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REFERENCES
Andersen, J. S., & Mann, M. (2000). Functional genomics by mass spectroscopy. FEBS Letters, 480, 25–31.
Anderson, L., & Seihamer, J. A. (1997). A comparison of selected mRNA and protein abundance in human liver. Electrophoresis, 18, 533–537.
Ashley-Koch, A., Wolpert, C. M., Menold, M. M., Zaeem, L., Basu, S., Donnelly, S. L., Ravan, S. A., Powel, C. M., Qumsiyeh, M. B., Aylsworth, A. S., Vance, J. M., Gilbert, J. R., Wright, H. H., Abramson, R. K., Delong, G. R., Cuccaro, M. L., & Pericak-Vance, M. A. (1999). Genetic studies of autistic disorder and chromosome 7. Genomics, 61, 227–236.
Bailey, A., Le Couteur, A., Gottesman, L., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995) Autism as a strongly genetic disorder: Evidence from a British twin study. Psychological Medicine, 25, 63–77.
Banks, R. E., Dunn, M. J., Hochstrasser, D. F., Sanchez, J-C, Blackstock, W., Pappin, D. J., & Selby, P. J. (2000). Proteomics: New perspectives, new biomedical opportunities. Lancet, 356, 1749–1756.
Barrett, S., Beck, J. C., Bemier, R., et al. (1999). Collaborative linkage study of autism (CLSA). An autosomal genome screen for autism. American Journal of Medical Genetics, 88, 609–615.
Bass, M. P., Menold, M. M., Wolpert, C. M., Donnelly, S. L., Ravan, S. A., Hauser, E. R., Maddox, L. O., Vance, J. M., Abramson, R. K., Wright, H. H., Gilbert, J. R., Cuccaro, M. L., DeLong, G. R., & Pericak-Vance, M. A. (2000). Genetic studies in autistic disorder and chromosome 15. Neurogenetics, 2, 219–226.
Buxbaum, J. D., Silverman, J. M., Smith, C. J., Kilifarski, M., Reichert, J., Hollander, E., Lawlor, B. A., Fitzgerald, M., Greenberg, D. A., & Davis, K. L. (2001). Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. American Journal of Human Genetics, 68, 1514–1520.
Chambers, G., Lawrie, L., Cash, P., & Murray, G. I. (2000). Proteomics: A new approach to the study of disease. Journal of Pathology, 192, 280–288.
Cook, E. H., Courchesne, R. Y., Cox, N. J., Lord, C., Gonen, D., Guter, S. J., Lincoln, A., Nix, K., Haas, R., Leventhal, B. L., & Courchesne, E. (1998). Linkage-disequilibrium mapping of autistic disorder, with 15q11–13 markers. American Journal of Human Genetics, 62, 1077-1083.
Fountoulakis, M., Schuller, E., Hardmeier, R., Berndt, P., & Lubec, G. (1999). Rat brain proteins: Two-dimensional protein database and variations in the expression level. Electrophoresis, 20, 3572–3579.
International Molecular Genetic Study of Autism Consortium (IMGSAC). (1998). A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Human Molecular Genetics, 7, 571–578.
Junaid, M. A., Sklower-Brooks, S., Wisniewski, K. E., & Pullarkat, R. K. (1999). A novel assay for lysosomal pepstatin-insensitive proteinase and its application for the diagnosis of late-infantile neuronal ceroid lipofuscinosis. Clinica Chimica Acta, 281, 169–176.
Langen, H., Berndt, P., Roder, D., Cairns, N., Lubec, G., & Fountoulakis, M. (1999). Two-dimensional map of human brain proteins. Electrophoresis, 20, 907–916.
Maestrini, E., Paul, A., Monaco, A. P., & Bailey, A. (2000). Identifying autism susceptibility genes. Neuron, 28, 19–24.
Philippe, A., Martinez, M., Bataille-Guillot, M., Gillberg, C., Rastam, M., Sponheim, E., Coleman, M., Zappella, M., Aschauer, H., van Malldergerme, L., Penet, C., Feingold, J., Brice, A., & Leboyer, M. (1999). Genome-wide scan for autism susceptibility genes. Human Molecular Genetics, 8, 805–812.
Pickles, A., Bolton, P., Macdonald, H., Bailey, A., Le Couteur, A., Sim, C-H., & Rutter, M. (1995). Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: A twin and family history study of autism.American Journal of Human Genetics, 57, 717–726.
Povey, A., Burley, M. W., Attwood, J., Benham, F., Hund, D., Jeremiah, S. J., Franklin, S., Gillett, G., Malas, S., Robson, E. B., Tippett, P., Edwards, J. H., Kwiatkowski, D. J., Super, M., Mueller, R., Fryer, A., Clarke, A., Webb, D., & Osborne, J. (1994). Two loci for tuberous sclerosis: One on 9q34 and one on 16p13. Annals of Human Genetics, 58, 107–127.
Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., Kalaydjieva, L., McCague, P., Dimiceli, S., Pitts, T., Nguyen, L., Yang, J., Harper, C., Thorpe, D., Vermeer, S., Young, H., Hebert, J., Lin, A., Ferguson, J., Chiotti, C., Wiese-Slater, S., Rogers, T., Salmon, B., Nicholas, P., Petersen, P. B., Pingree, C., McMahon, W., Wong, D. L., Cavalli-Sforza, L. L., Kraemer, H. C., & Myers, R. M. (1999). A genomic screen for autism: Evidence for a multilocus etiology. American Journal of Human Genetics, 65, 493–507.
Santoni, V., Molloy, M., & Rabilloud, T. (2000). Membrane proteins and proteomics: Un amour impossible? Electrophoresis, 21, 1054–1070.
Sleat, D. E., Donnelly, R. J., Lackland, H., Liu, C-G., Sohar, I., Pullarkat, R. K., & Lobel, P. (1997). Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science, 277, 1802–1804.
Suzuki, Y., Sakuraba, H., & Dshima, A. (1995). ?-galactosidase deficiency (?-galactosidosis); GM1 gangliosidosis and Morquio B disease. In The metabolic and molecular bases of inherited disease, (vol. II) (pp. 2785–2873) Scriver, C. R. et al. (Eds.), New York: McGraw-Hill.
Szatmari, P., Jones, M. B., Zwaigenbaum, L., & MacLean, J. E. (1998). Genetics of autism: Overview and new directions. Journal of Autism and Developmental Disorders, 28, 351–368.
Tsuji, T., Shimohama, S., Kamiya, S., Sazuka, T., & Ohara, O. (1999). Analysis of brain proteins in Alzheimer's disease using high-resolution two-dimensional gel electrophoresis. Journal of Neurological Science, 166, 100–106.
Wilkins, M. R., Sanchez, J. C., Gooley, A. A., Appel, R. D., Humphery-Smith, I., Hochstrasser, D. F., & Williams, K. L. (1996). Progress with proteome projects: Why all proteins expressed by a genome should be identified and how to do it.Biotechnology and Genetics Engineering Review, 13, 19–20.
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Junaid, M.A., Pullarkat, R.K. Proteomic Approach for the Elucidation of Biological Defects in Autism. J Autism Dev Disord 31, 557–560 (2001). https://doi.org/10.1023/A:1013242910574
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DOI: https://doi.org/10.1023/A:1013242910574