title: Role of UBE3A and ATP10A genes in autism susceptibility region 15q11-q13 in an Italian population: a positive replication for UBE3A.
abstract: The aetiology of autism is still largely unknown despite analyses from family and twin studies demonstrating substantial genetic role in the aetiology of the disorder. Data from linkage studies and analyses of chromosomal abnormalities identified 15q11-q13 as a region of particular aetiopathogenesis interest. We screened a set of markers spanning two known imprinted, maternally expressed genes, UBE3A and ATP10A, harboured in this candidate region. We replicated evidence of linkage disequilibrium (LD) at marker D15S122, located at the 5' end of UBE3A and originally reported by Nurmi et al. (2001). The potential role of UBE3A in our family-based association study is further supported by the association of two haplotypes that include one of the alleles of D15S122 and by the transmission disequilibrium test (TDT) evidence of the same allele in a parent of origin effect analysis. In a secondary analysis, we provided the first evidence of a significant association between first word delay and psychomotor regression with the 15q11-q13 region. Our data support a potential role of UBE3A in the complex pathogenic mechanisms of autism.
authors.affiliation: Università degli Studi di Milano, Milan, Italy.
authors.forename: Guia
authors.initials: G
authors.lastname: Guffanti
authors.forename: Luisa
authors.initials: L
authors.lastname: Strik Lievers
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bonati
authors.forename: Margherita
authors.initials: M
authors.lastname: Marchi
authors.forename: Lupo
authors.initials: L
authors.lastname: Geronazzo
authors.forename: Nardo
authors.initials: N
authors.lastname: Nardocci
authors.forename: Margherita
authors.initials: M
authors.lastname: Estienne
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D001321:Autistic Disorder / Q000150:complications / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004261:DNA Replication; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases; C426648:ATP10A protein, human