Autistic disorder is a severe disorder of cognitive, language, and social development. Several studies have indicated genetic predisposition to the development of autistic disorder in children. Subjects with suspected autistic disorder will be diagnosed by use of the parent interview, Autism Diagnostic Interview-Revised (ADI-R) and clinical DSM-IV diagnosis based on interview of the child with the Autism Diagnostic Observation Schedule (ADOS) and review of the transcript of the ADI-R parent interview without access to the ADI-R scoring. Subjects will he excluded from genetic analysis if their mental age is less than 18 months or if they have Fragile X syndrome, phenylketonuria, tuberous sclerosis, or other identifiable chromosomal disorders. These subjects with autistic disorder will be studied to determine if there is an association between the primary candidate genes, serotonin 5-HT2A receptor, 5-HT7 receptor, 5-HT transporter, and dopamine D2 receptor and autistic disorder. In addition, the following secondary candidate genes will he studied: (5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A, 5-HT6), other dopamine receptors (D1, D3, D4, D5), enzymes involved in serotonin and/or dopamine metabolism or transport (tryptophan hydroxylase, tyrosine hydroxylase, dopamine-beta-hydroxylase, dopamine transporter, aromatiC amino acid decarboxylase, monoamine oxidase (MAO)-A and MAO-B). C-Harvey-Ras-1 (HRAS) will be studied because of a previous association found in autistic disorder without using intrafamilial controls. The haplotype-based Haplotype Relative Risk (HRR) method will be used to assess the overall evidence for association between alleles at the above candidate genes and autistic disorder. If a significant association between alleles at any of these candidate genes and autistic disorder is found, the Transmission/Disequilibrium Test (TDT) will be used to determine whether the observed association is due to linkage between the marker and susceptibility to autistic disorder. The statistical methods have been chosen to reduce the change of a false positive result due to population stratification.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH052223-01A2
Application #
2251833
Study Section
Child Psychopathology and Treatment Review Committee (CPT)
Project Start
1995-09-30
Project End
2000-08-31
Budget Start
1995-09-30
Budget End
1996-08-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Brune, Camille W; Kim, Soo-Jeong; Salt, Jeff et al. (2006) 5-HTTLPR Genotype-Specific Phenotype in Children and Adolescents With Autism. Am J Psychiatry 163:2148-56
Herzing, Laura B K; Cook Jr, Edwin H; Ledbetter, David H (2002) Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications. Hum Mol Genet 11:1707-18
Veenstra-VanderWeele, Jeremy; Kim, Soo-Jeong; Lord, Catherine et al. (2002) Transmission disequilibrium studies of the serotonin 5-HT2A receptor gene (HTR2A) in autism. Am J Med Genet 114:277-83
Kim, S-J; Young, L J; Gonen, D et al. (2002) Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 7:503-7
Kim, S-J; Cox, N; Courchesne, R et al. (2002) Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder. Mol Psychiatry 7:278-88
Kim, Soo-Jeong; Herzing, Laura B K; Veenstra-VanderWeele, Jeremy et al. (2002) Mutation screening and transmission disequilibrium study of ATP10C in autism. Am J Med Genet 114:137-43
Herzing, L B; Kim, S J; Cook Jr, E H et al. (2001) The human aminophospholipid-transporting ATPase gene ATP10C maps adjacent to UBE3A and exhibits similar imprinted expression. Am J Hum Genet 68:1501-5
Cook Jr, E H (2001) Genetics of autism. Child Adolesc Psychiatr Clin N Am 10:333-50
Owley, T; McMahon, W; Cook, E H et al. (2001) Multisite, double-blind, placebo-controlled trial of porcine secretin in autism. J Am Acad Child Adolesc Psychiatry 40:1293-9
Kim, S J; Cook Jr, E H (2000) Novel de novo nonsense mutation of MECP2 in a patient with Rett syndrome. Hum Mutat 15:382-3

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