Microarray analysis of gene/transcript expression in Angelman syndrome: deletion versus UPD.

Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics and University of Missouri at Kansas City School of Medicine, 2401 Gillham Road, Kansas City, MO 64108, USA. dbittel@cmh.edu

Angelman syndrome (AS) is a neurodevelopmental disorder due to a functional deficit, usually a deletion, of the UBE3A gene located in the 15q11-q13 chromosome region. We report the first microarray analysis of gene expression in AS using a custom cDNA microarray to compare expression patterns from lymphoblastoid cell lines from control males and AS subjects with a 15q deletion or uniparental paternal disomy 15. Expression patterns of genes known to be biallelically expressed or paternally or maternally expressed were consistent with expectations. We detected paternal or maternal allelic bias in the expression of several genes and transcripts (e.g., GABRA5, GABRB3, WI-14946). Additionally, mechanisms controlling paternal allele expression appear to be faithfully replicated in each paternal chromosome in individuals with paternal disomy. Our results indicate that interconnected mechanisms can produce subtle and unexpected changes in gene expression that may help explain the phenotypic differences observed among the genetic subtypes of AS.

PMID: 15607424 [PubMed - indexed for MEDLINE]