Genome-wide association and copynumber variation analyses in Japanese individuals with autism.

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791323
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: ISMAIL Thanseem 浜松医科大学, 医学部, 特任研究員 (60569846)
• Project Period (FY): 2011 – 2012
• Keywords: 臨床精神分子遺伝学 / 児童・思春期精神医学 / 自閉症 / コピー数多型

Research Abstract

Aim of the current study was first to examine the DNA copy number variations (CNVs) that could be associated with autism in Japanese population. We analyzed samples from subjects with autism and their parents (trio) with Affymetrix Genome Wide SNP 6.0 array. A total of 150 trio samples were analyzed. Only the samples which passed the required quality control (contrast QC >0.4) were used in subsequent analyzes. Averages of 39.37 autosomal CNVs are detected per patient samples, after all the QC corrections. There is no significant difference in the total number/average size of CNVs per sample between patients and their parents. However, the percentage of deletions in the total length of CNVs is 42.5% in case of patients, whileit is only 34% and 28.4% in father and mother samples respectively. Above 90% of the CNVs in children are found to be inherited; almost equally from both the parents. Among the CNVs which are spanning genes, 74.5% are deletions in the case of de novo events; it’s only 53% in inherited cases. Toidentify the most important de novo events, the CNVs are further screened based on the mean LRR values of all the probes within a CNV. Finally, 142 highly confident de novo CNVs were identified; among them 124 are spanning exons, and hence supposed to have some functional significance. Among these 124 CNVs, 18 are found be rare de novo events. These 18 rare de novo events were validated with qPCR using SyBr Green. 12 of them were found to be true positive calls while remaining werefalse calls. A few potential candidate genes with a possible role in neurodevelopment were identified.

Research Products

• [Journal Article] Brain-region specific altered expression, and association of mitochondria-related genes in autism (2012)
  • Author(s): Anitha A, Nakamura K, Thanseem I, Yamada K, Iwayama Y, Toyota T, Matsuzaki H, Miyachi T, Yamada S, Tsujii M, Tsuchiya KJ, Matsumoto K, Iwata Y, Suzuki K, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N
  • Journal Title: Mol Autism Volume: 3(1) Pages: 12
• [Journal Article] H. B. C. Study Team. Seasonal variations of neuromotor development by 14 months of age: Hamamatsu Birth Cohort for mothers and children (HBC Study) (2012)
  • Author(s): Tsuchiya KJ, Tsutsumi H, Matsumoto K, Takei N, Narumiya M, Honda M, Thanseem I, Anitha A, Suzuki K, Matsuzaki H, Iwata Y, Nakamura K, Mori N
  • Journal Title: PLoS One Volume: 7(12) Pages: e52057
• [Journal Article] Vldlr overexpression causes hyperactivity in rats (2012)
  • Author(s): Iwata K, Izumo N, Matsuzaki H, Manabe T, Ishibashi Y, Ichitani Y, Yamada Y, Thanseem I, Anitha A, Vasu MM, Shimmura C, Wakuda T, Kameno Y, Takahashi T, Iwata Y, Suzuki K, Nakamura K, Mori N
  • Journal Title: Mol Autism Volume: 3(1) Pages: 11
• [Journal Article] Protocadherin α(PCDHA) as a novel susceptibility gene for autism (2012)
  • Author(s): Anitha A, Thanseem I (equal contribution), Nakamura K, Yamada K, Iwayama Y, Toyota T, Iwata Y, Suzuki K, Sugiyama T, Tsujii M, Yoshikawa T, Mori N
  • Journal Title: J Psychiatry Neurosci Volume: 37(6) Pages: 120058
• [Journal Article] Elevated transcription factor Sp1 in autism brains alters the expression of autism candidate genes (2012)
  • Author(s): Thanseem I, Anitha A, Nakamura K, Suda S, Iwata K, Matsuzaki H, Ohtsubo M, Ueki T, Katayama T, Iwata Y, Suzuki K, Minoshima S, Mori N
  • Journal Title: Biol Psychiatry Volume: 71(5) Pages: 410-418
• [Journal Article] Association of transcription factor gene LMX1B with autism (2011)
  • Author(s): Thanseem I, Nakamura K, Anitha A, Suda S, Yamada K, Iwayama Y, Toyota T, Tsujii M, Iwata Y, Suzuki K, Matsuzaki H, Iwata K, Sugiyama T, Yoshikawa T, Mori N
  • Journal Title: PLoS ONE. Volume: 6(8) Pages: e23738
• [Journal Article] Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism (2011)
  • Author(s): Suda S, Iwata K, Shimmura C, Kameno Y, Anitha A, Thanseem I, Nakamura K, Matsuzaki H, Tsuchiya KJ, Sugihara G, Iwata Y, Suzuki K, Koizumi K, Higashida H, Takei N, Mori N
  • Journal Title: Mol Autism Volume: 2(1) Pages: 14
• [Presentation] Rare de novo copy number variation in Japanese autism subjects (2012)
  • Organizer: at the 8th Hamamatsu Medical Science symposium
  • Place of Presentation: Hamamatsu, Japan
  • Year and Date: 20121100
• [Presentation] De novo copy number variation in Japanese autism subjects (2012)
  • Organizer: the 20th World Congress of Psychiatric Genetics
  • Place of Presentation: Hamburg, Germany
  • Year and Date: 20121000