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Behavioral Science Research

Behavioral Science Research. Munroe – Meyer Institute for Genetics and Rehabilitation. Clinical Activities. Rate limiting step…. Omaha Clinics Behavioral Genetics. Neurogenetics Neurosensory Genetics Pediatric / Adult metabolic disorders

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Behavioral Science Research

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  1. Behavioral Science Research Munroe – Meyer Institute for Genetics and Rehabilitation

  2. Clinical Activities Rate limiting step…..

  3. Omaha ClinicsBehavioral Genetics • Neurogenetics • Neurosensory Genetics • Pediatric / Adult metabolic disorders • Fetal Alcohol Syndrome (Screening and comprehensive)

  4. Omaha ClinicsDevelopmental / Behavioral • Developmental Medicine Clinics • Behavioral Health Clinics • GWR autism consultative clinics • Neurobehavioral clinic • Behavioral Management Clinics • Transition Clinic • Advanced Autism Management Clinic

  5. Outreach ClinicsIn Neurobehavioral Genetics (2006) . . . Pierre Rapid City . . . . Scottsbluff Winnebago . North Platte Kearney

  6. Defining ‘Endophenotypes’

  7. Endophenotype Analysis • Applied Behavioral Analysis of autism • Neuropsychologic assessment of reading disabilities • Characterization of sleep disorders • Genetic categorization of mental retardation and cerebral palsy

  8. Molecular Genetics

  9. Core Facilities • Complex linkage analysis • Commercial and customized fluorescence –in situ hybridization (FISH) • Wave (DHPLC) screening • High throughput gene sequencing • Customized chip micro-array • ‘Knock out’ mouse facilities • ‘Knock down’ facilities • Whole genome array SNP typing • (TBA) Whole genome SNP typing • Epigenetic modifications (DNA methylation)

  10. Areas of Emphasis

  11. Behavioral Genetics • Autism • Apraxia • Dyslexia • ADHD • Neurosensory disorders

  12. Behavioral / Developmental • Integrated Behavioral Health in Rural Primary Care Practice • Pediatric Feeding Disorders • Augmentative Communication • Brain Injury Training • Medical Transition • Program Evaluation • Early Childhood Development • Teratogenic Effects on Early Childhood • Systematic Developmental Follow-up

  13. Psychiatry • Depression (children, adolescents, adults) • pharmacotherapy, psychotherapy, genetics, immune function, vagal nerve stimulation, prevention in head & neck cancer) • Anxiety • pharmacotherpy • Alzheimer's Disease • pharmacotherapy for cognition & apathy • ADHD (children, adolescents, adults) • pharmacotherapy, genetics, rating scale development • Gambling • pharmacotherapy • Consult Liaison

  14. How it all works together

  15. Genetics of Dyslexia • Twin and family studies establish genetic influence on reading ability • Heritability ~ 0.56 • Segregation analysis gives evidence for several major genes • Analyses to identify heritable “endophenotypes” • Phonemic awareness, phonological coding, orthographic coding, single word reading

  16. Localization of genes that influence dyslexia • Positional cloning: • Linkage and association analysis • DNA marker typing across the chromosomes leads to identification of markers in a chromosomal region that are inherited along with dyslexia. • Genes in this region are investigated to identify mutations or variants in association with the phenotype • Chromosomal abnormality: • Identification of a gene disrupted by chromosome breakage

  17. Reading Disability Loci and Phenotypes

  18. DYX2: 6p22.2: Linkage Analysis LOD score 0 0.5 1.0 1.5 2.0 2.5 25.3 25.2 0 D6S1605 25.1 D6S274 24.3 24.2 24.1 2 23 22.3 D6S1567 22.2 4 22.1 p 21.33 21.32 21.3 6 1 21.2 D6S422 21. 8 1 D6S1597 12.3 D6S1588 12.2 10 12. 1 11. 11. 2 1 11. D6S461 11. 1 2 12 12 D6S276 Position (cM) 13 D6S1554 14 14. D6S1571 1 14.2 14.3 D6S105 D6S306 16 15 D6S258 D6S1683 MOG3132 16. D6S273 1 16.2 18 16.3 D6S1568 D6S439 21 20 22.1 D6S291 q 22.2 22 22.31 D6S1019 22.32 22.33 24 23.1 23.2 26 23.3 24.1 24.2 24.3 25.1 25.2 25.3 26 OC PA 27 Discrim

  19. VMP DCDC2 KIAA0319 TTRAP THEM2 Deffenbacher et al., 2004 KIAA0319 TTRAP Francks et al., 2004 DYX2: 6p22: Association Analysis

  20. PNAS 102:17053-17058 (2005) DYX2: 6p22.2: DCDC2

  21. Figure 3. Interference with KIAA0319 disrupts radial migration in the developing rat neocortex. (A) Depiction of in utero electroporation assay for neuronal migration in fetal neocortex. Combinations of plasmids coding for shRNAs, eGFP and KIAA0319 were injected into the ventricles of the E14 rat forebrain, in order to transfect neuronal progenitor cells at the VZ surface. Over the course of 4 days, neurons migrated radially towards the IZ and CP. (B) Average distance migrated by neurons 4 days following co-transfection of eGFP and one the following five plasmids: (i) KIAA0319shRNA; (ii) shRNA containing scrambled sequence of a KIAA0319shRNA vector. Paracchini et al., Hum. Molec. Genet. 15: 1659-1666, 2006

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