Linkage Disequilibrium at the Angelman Syndrome Gene UBE3A in Autism Families

• Published in: Genomics (San Diego, Calif.) Vol. 77; no. 1-2; pp. 105 - 113
• Main Authors: Nurmi, Erika L., Bradford, Yuki, Chen, Yi-hui, Hall, Jenifer, Arnone, Brenda, Gardiner, Mary Beth, Hutcheson, Holli B., Gilbert, John R., Pericak-Vance, Margaret A., Copeland-Yates, Susan A., Michaelis, Ron C., Wassink, Thomas H., Santangelo, Susan L., Sheffield, Val C., Piven, Joseph, Folstein, Susan E., Haines, Jonathan L., Sutcliffe, James S.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.09.2001; Elsevier
• Subjects: Alleles; Angelman syndrome; Angelman Syndrome - genetics; Autistic Disorder - genetics; Base Sequence; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 15 - genetics; DNA - chemistry; DNA - genetics; DNA Mutational Analysis; Family Health; Female; Fundamental and applied biological sciences. Psychology; GABRA5 gene; GABRB3 gene; GABRG3 gene; Gene Frequency; Genes. Genome; Genotype; Humans; Ligases - genetics; Linkage Disequilibrium; Male; Microsatellite Repeats; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Polymorphism, Single Nucleotide; Protein Subunits; Receptors, GABA-A - genetics; Sequence Deletion; UBE3A gene; Ubiquitin-Protein Ligases; 15q11–q13; UBE3A; deletion; autism; linkage disequilibrium; Genetic mapping; Autism; Nervous system diseases; Linkage; Multigene family; Developmental disorder; Neurological disorder; Syndrome
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2001.6617

Autistic disorder is a neurodevelopmental disorder with a complex genetic etiology. Observations of maternal duplications affecting chromosome 15q11–q13 in patients with autism and evidence for linkage and linkage disequilibrium to markers in this region in chromosomally normal autism families indicate the existence of a susceptibility locus. We have screened the families of the Collaborative Linkage Study of Autism for several markers spanning a candidate region covering ∼2 Mb and including the Angelman syndrome gene (UBE3A) and a cluster of γ-aminobutyric acid (GABAA) receptor subunit genes (GABRB3, GABRA5, and GABRG3). We found significant evidence for linkage disequilibrium at marker D15S122, located at the 5′ end of UBE3A. This is the first report, to our knowledge, of linkage disequilibrium at UBE3A in autism families. Characterization of null alleles detected at D15S822 in the course of genetic studies of this region showed a small (∼5-kb) genomic deletion, which was present at somewhat higher frequencies in autism families than in controls.