Behavioral Science Research

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
.
.
.
.
Winnebago
Scottsbluff
.
North Platte
Kearney
6
(No Transcript)
7
Defining Endophenotypes
8
Endophenotype Analysis

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

9
Molecular Genetics
10
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)

11
Areas of Emphasis
12
Behavioral Genetics

• Autism
• Apraxia
• Dyslexia
• ADHD
• Neurosensory disorders

13
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

14
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

15
How it all works together
16
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
17
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

18
Reading Disability Loci and Phenotypes
Locus Region Population Phenotype
DYX8 1p36 N. Carolina Washington Phonological Decoding, RAN
DYX3 2p11 Norway UK Reading and Spelling
DYX5 3p12-q13 Finland Phonologic Awareness
DYX2 6p22 N. CarolinaColorado, UK Phonemic AwarenessOrthographic Choice, Phonologic Decoding
DYX4 6q11-2 Canada Phonologic Decoding
7q32 Norway Reading and Spelling
DYX7 11p15.5 Canada Phonologic Decoding
DYX1 15q21 N. CarolinaGermanyNorway Single Word ReadingSpellingReading and Spelling
DYX6 18p11 Colorado, UK Single word reading, Orthographic Coding
DYX9 Xq27.3 Colorado, UK, Holland Multiple phenotypes

19
DYX2 6p22.2 Linkage Analysis
20
DYX2 6p22 Association Analysis
21
DYX2 6p22.2 DCDC2
22
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