title: Family-based transmission analysis of HLA genetic markers in Sardinian children with autistic spectrum disorders.
abstract: Analyses of a 6-Mb region spanning the human leukocyte antigen (HLA) region from the HLA-DR to the HFE gene were performed in 37 families of Sardinian ancestry, all of whom had at least one autistic child, to identify genetic markers associated with autism spectrum disorders (ASD) development. In particular, four microsatellites (MIB, D6S265, MOGc, and D6S2239) and three single-nucleotide polymorphisms (SNPs; two in positions -308 and -238 in the promoter of the TNF-alpha and SNP rs2857766 [V142L] in exon 3 of the MOG gene) were analyzed. An intrafamilial case-control method (affected family-based controls) and transmission disequilibrium test analysis were used to evaluate the association of microsatellite and SNP markers with ASD-affected children. Results indicated positive associations with ASD for D6S265*220 (p < 0.01) and MOGc*131 (p < 0.05) and negative associations for MOGc*117 and MIB*346 alleles (p < 0.01) in ASD children. Polymorphism haplotype analysis indicated that D6S265 allele *220 and MOGc allele *131 were significantly more likely to be transmitted together, as a whole haplotype, to ASD children (p < 0.05). Conversely, the D6S265*224-MOGc*117-rs2857766(G) haplotype was significantly less frequently transmitted to ASD children (p < 0.01). The results present novel gene markers, reinforcing the hypothesis that genetic factors play a pivotal role in the pathogenesis of ASD.
authors.affiliation: Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, S. Maria Nascente, Milan, Italy. fguerini@dongnocchi.it
authors.forename: Franca R
authors.initials: FR
authors.lastname: Guerini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolognesi
authors.forename: Salvatorica
authors.initials: S
authors.lastname: Manca
authors.forename: Stefano
authors.initials: S
authors.lastname: Sotgiu
authors.forename: Milena
authors.initials: M
authors.lastname: Zanzottera
authors.forename: Cristina
authors.initials: C
authors.lastname: Agliardi
authors.forename: Sonia
authors.initials: S
authors.lastname: Usai
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005819:Genetic Markers / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D005819:Genetic Markers; C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; C571326:MOG protein, human; D008565:Membrane Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases