The purpose of this K23 application is to foster scientific development and clinical investigational skills of the candidate. The candidate has had structured clinical training in psychiatry/child psychiatry and research training with Dr. Ed Cook studying molecular genetic bases of childhood-onset psychiatric disorders. The candidate will expand her research skills through a unique integration of expertise from diverse resources and customized career development plan. The research plan focuses on investigation of genetic underpinnings of restricted repetitive behavior (RRB). RRB is a term to describe a wide variety of abnormal repetitive behavior (e.g., stereotypy, repetitive forms of self-injurious behavior, obsession, compulsion, ritualistic behavior, sameness behavior and restricted interests). RRB is one of the core features of autism spectrum disorders (ASDs) and is also commonly observed in Prader-Willi syndrome (PWS). RRB frequently dominates daily activities of affected individuals, interferes with opportunities to develop functional behaviors, and requires intervention and treatment. Despite functional significance of RRB, little is known about underlying genetic mechanism. In this K23 application, the candidate proposes to examine genetic variations within the chromosome 15q11-q13 region and to test association between genetic variants and specific forms of RRB among individuals with PWS and children with ASD. The long-term goal of this project is to understand the common neurobiological mechanism for RRB across the clinical categories. The candidate's training background in clinical psychiatry and molecular genetics provides an excellent foundation for this work. The Career Development Plan is designed for the candidate to develop her research skills by (1) the mentorship of Drs. Mark Lewis, Dan Driscoll, and Ed Cook, who have expertise in RRB/animal models, PWS/genomic imprinting, and autism/molecular genetics, respectively;(2) specific training in assessments of autism, PWS, and RRB;(3) consultation with experts in statistical genetics and high-throughput SNP genotyping;(4) formal didactic training in disciplines including study design, data analysis, epidemiology, and ethics;(5) attendance and presentation in scientific meetings, and (6) the proposed study. Given her prior training, proposed mentorship, and outstanding resources, this K23 Award will permit the candidate to become an independent clinical investigator in the field of neurodevelopmental genetic disorders.
Our ultimate research aim is to identify genetic factors for restricted repetitive behavior (RRB) across two clinical entities: autism spectrum disorders (ASDs) and Prader-Willi syndrome (PWS). Therefore, positive results from this study should provide valuable insights into pathogenesis and novel treatment of RRB among individuals with these chronic and devastating clinical conditions.
|Chaste, Pauline; Sanders, Stephan J; Mohan, Kommu N et al. (2014) Modest impact on risk for autism spectrum disorder of rare copy number variants at 15q11.2, specifically breakpoints 1 to 2. Autism Res 7:355-62|
|Kim, Young Shin; Fombonne, Eric; Koh, Yun-Joo et al. (2014) A comparison of DSM-IV pervasive developmental disorder and DSM-5 autism spectrum disorder prevalence in an epidemiologic sample. J Am Acad Child Adolesc Psychiatry 53:500-8|
|Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J et al. (2013) Adjusting head circumference for covariates in autism: clinical correlates of a highly heritable continuous trait. Biol Psychiatry 74:576-84|
|Kim, Soo-Jeong; Miller, Jennifer L; Kuipers, Paul J et al. (2012) Unique and atypical deletions in Prader-Willi syndrome reveal distinct phenotypes. Eur J Hum Genet 20:283-90|
|Henkhaus, Rebecca S; Kim, Soo-Jeong; Kimonis, Virginia E et al. (2012) Methylation-specific multiplex ligation-dependent probe amplification and identification of deletion genetic subtypes in Prader-Willi syndrome. Genet Test Mol Biomarkers 16:178-86|
|Jacob, Suma; Brune, Camille W; Badner, Judith A et al. (2011) Family-based association testing of glutamate transporter genes in autism. Psychiatr Genet 21:212-3|
|Kim, Young Shin; Leventhal, Bennett L; Koh, Yun-Joo et al. (2011) Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 168:904-12|
|Flores, Cindi G; Valcante, Gregory; Guter, Steve et al. (2011) Repetitive behavior profiles: Consistency across autism spectrum disorder cohorts and divergence from Prader-Willi syndrome. J Neurodev Disord 3:316-24|
|Lewis, Mark; Kim, Soo-Jeong (2009) The pathophysiology of restricted repetitive behavior. J Neurodev Disord 1:114-32|