Abstract
Imprinting is the naturally occurring functional inequality of alleles of a given gene reflecting their parental origin. Only one of the alleles (either maternal or paternal) is functional (producing mRNA) in an imprinted gene. Imprinted genes in the human genome have been identified and are sometimes associated with particular disorders. The two best-known conditions in human genetics that are the result of imprinted gene abnormalities are Prader-Willi (PWS) and Angelman (AS) syndromes. These two clinically distinct neurobehavioral disorders are the result of absent/deficient function of alleles of genes in the paternally (PWS) or maternally (AS) derived proximal segment of the long arm of chromosome 15 (15q11?ql3). This chromosomal region is normally imprinted. At least four genes in this region were found to be expressed only by paternally derived alleles (1) and the deficiency of these and possibly other gene products in the region is believed to result in Prader-Willi syndrome. One gene, UBE3A, located within the PWS/ AS region was found to be expressed in certain tissues only by its maternally derived allele. Mutations in this gene are associated with some cases of AS (2).
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References
Lee, S. and Wevrick, R. (2000) Identification of novel imprinted transcripts in the Prader-Willi syndrome and Angelman syndrome deletion region: further evidence for regional imprinting control. Am. J. Hum. Genet. 66 (3), 848–858.
Kishino, T., Lalande, M, Wagstaff, J. (1997) UBE3A/E6-AP mutations cause Angelman syndrome. Nature Genet. 16, 16.
American Society of Human Genetics/American College of Medical Genetics Test and Technology Transfer Committee (1996): Diagnostic Testing for Prader-Willi and Angelman Syndromes: Report of the ASHG/ACMG Test and Technology Transfer Committee. Am. J. Hum. Genet. 58, 1085–1088.
Ohta, T., Buiting, K., Kokkonen, H., McCandless, S., Heeger, S., Leisti, H., et al. (1999) Molecular mechanism of Angelman syndrome in two large families involves an imprinting mutation. Am. J. Hum. Genet. 64(2), 385–396.
Zeschnigk, M., Schmitz, B., Dittrich, B., Buiting, K., Horsthemke, B., and Doerfler, W. (1997) Imprinted segments in the human genome: different DNA methylation patterns in the Prader-Willi/Angelman syndrome region as determined by the genomic sequencing method. Hum. Mol. Genet. 6, 3875395.
Kubota, T., Das, S., Christian, S. L., Baylin, S. B., Herman, J. G., and Ledbetter, D. H. (1997) Methylation-specific PCR simplifies imprinting analysis. Nature Genet. 16, 16.
Velinov, M., Gu, H., Genovese, M., Duncan, C., Brown, W. T., and Jenkins, E. (2000) The feasibility of PCR-based diagnosis of Prader-Willi and Angelman syndromes using restriction analysis after bisulfite modification of genomic DNA. Mol. Genet. Metab. 69, 81–83.
Clark, S., Harrison, J., Paul, C. L., and Frommer, M. (1994) High sensitivity mapping of methylated cytosines, Nucleic Acids Res. 22, 2990–2997.
Zeschnigk, M, Lich, C., Buiting, K., Doerfler, W., and Horsthemke, B. (1997) A single tube PCR test for the diagnosis of Angelman and Prader-Willi syndrome based on allelic methylation differences at the SNRPN locus. Eur. J. Hum. Genet. 5, 94–98.
Velinov, M., Gu, H., Shah, K., Genovese, M., Duncan, C., Kupchik, G., and Jenkins, E. C. (2001) PCR-based methylation testing for Prader-Willi or Angelman syndromes using archived fixed-cell suspensions. Genet. Test. 5, 153–155.
Kaczmarski, A. and Rosenblum M. (1999) Carrier detection and patient diagnosis of genetic mutations using a mini-gel electrophoresis system. Am. Biotech. Lab. 17, 28.
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Velinov, M., Jenkins, E.C. (2003). PCR-Based Strategies for the Diagnosis of Prader-Willi/Angelman Syndromes. In: Potter, N.T. (eds) Neurogenetics. Methods in Molecular Biology™, vol 217. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-330-5:209
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DOI: https://doi.org/10.1385/1-59259-330-5:209
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