GENOME ORGANIZATION, FUNCTION, AND IMPRINTING IN PRADER-WILLI AND ANGELMAN SYNDROMES

The chromosomal region, 15q11-q13, involved in Prader-Willi and Angelman syndromes (PWS and AS) represents a paradigm for understanding the relationships between genome structure, epigenetics, evolution, and function. The PWS/AS region is conserved in organization and function with the homologous mo...

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Bibliographic Details
Published in:Annual review of genomics and human genetics 2001-01, Vol.2 (1), p.153-175
Main Authors: Nicholls, Robert D, Knepper, Jessica L
Format: Article
Language:English
Subjects:
Angelman Syndrome - genetics
Animals
chromatin
Chromosomes, Human, Pair 15
DNA Methylation
duplicon
epigenetic
Genomic Imprinting
Humans
polycistronic RNA
Prader-Willi Syndrome - genetics
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Summary:The chromosomal region, 15q11-q13, involved in Prader-Willi and Angelman syndromes (PWS and AS) represents a paradigm for understanding the relationships between genome structure, epigenetics, evolution, and function. The PWS/AS region is conserved in organization and function with the homologous mouse chromosome 7C region. However, the primate 4 Mb PWS/AS region is bounded by duplicons derived from an ancestral HERC2 gene and other sequences that may predispose to chromosome rearrangements. Within a 2 Mb imprinted domain, gene function depends on parental origin. Genetic evidence suggests that PWS arises from functional loss of several paternally expressed genes, including those that function as RNAs, and that AS results from loss of maternal UBE3A brain-specific expression. Imprinted expression is coordinately controlled in cis by an imprinting center (IC), a genetic element functional in germline and/or early postzygotic development that regulates the establishment of parental specific allelic differences in replication timing, DNA methylation, and chromatin structure.
ISSN:1527-8204
1545-293X
DOI:10.1146/annurev.genom.2.1.153