Introduction to Genetics and
Overview of the Conference
Paul Grossfeld, M.D.
Associate Adjunct Professor
UCSD School of Medicine
July 7, 2010
High resolution karyotype
High resolution karyotype
 Advantages
 “Whole
genome scan”
 Relative low cost
 Disadvantages
 Labor intensive
 Detection above 5 Mb
FISH Methodology
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Www.nhgri.nih.gov./DIR/VIP (Artist Darryl Leja)
FISH Analysis
 Advantages
 Highly
specific (100 kb)
 Microdeletions/Microduplications
 Disadvantages
 Highly specific
 500-600 probes needed to match
the power of karyotyping
Microdeletion Detection
Microdeletion Detection
FISH Analysis
To improve detection…
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G-banding alone is insufficient to identify
clinically significant deletions/duplications
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Additional molecular cytogenetic
technologies are needed that offer a whole
genome approach to submicroscopic
imbalances
Array-based Comparative Genomic
Hybridization
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Molecular cytogenetic method to detect copy
number imbalances
Capable of genome wide scanning
Less labor intensive
Objective method compared to routine
cytogenetic G-banding and FISH analysis
Methods
Isolate Genomic DNA from samples
 DNA digestion
 Label patient and control samples
 Hybridize to microarray
 Post hybridization washing
 Assay scanning and data analysis
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Array Design
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Resolution depends on clone size and
spacing
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Only detect unbalanced rearrangements
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Creates a “molecular karyotype”
Indications - Postnatal
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Multiple congenital anomalies
Developmental delay/ mental retardation of
unknown origin
Autism
Any individual suspected of a chromosomal
imbalance, even with normal karyotype
High resolution mapping to identify specific genes
Assay Requirements
Each laboratory must define criteria
for an abnormal result
 Confirmatory testing by G-banding or
FISH analysis
 Parental testing often needed to
interpret significance of results

Array Formats
High Resolution
1-3 Mb spacing across the genome
 50 – 75 kb resolution
 Oligonucleotides used to cover the
genome
 Approximately 50,000 clones
 Numerous polymorphisms identified

High Density Oligo CGH
Characterization of
known cytogenetic
rearrangements to
determine size and gene
content
Approximately 10%
imbalances detected in
individuals with normal
karytoype
Definition of 11q Terminal
Deletion Disorder
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Terminal Deletion in 11q
Either sporadic (normal parents, 90-95%) or inherited
(from a parent with a balanced translocation, 5-10%)
Can be an Inte ial Deletion (very rare)
NOT an noisrevnI
NOT a Balanced Translocation/Balanced Translocation
NOT a Duplicaplication
Balanced Translocation
Mechanisms of 11q- deletions
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Variation in deletion size
All breakpoints cluster around CCG repeats
The largest deletions are caused by CCG repeat
expansion/Fra11B fragile site
Smaller deletions: Not associated with a fragile
site
All of the smallest deletions are derived from the
paternal chromosome
Overview of the Conference
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Talks
Assessments
Dr. Sarah Mattson
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Review of what we have learned about your 11q
children
Rationale and logistics of the assessments
What we hope to learn and how this can help
your child
Traditional
Osteopathic Medicine
Kathryn Gill, M.D.
The effects of Neurogranin
on learning and memory in
11qAndras Bratincsak, MD, PhD
July 8th, 2010
The ETS-1 gene and heart defects
in 11q-: Clinical implications
Paul Grossfeld, M.D.
Associate Adjunct Professor
UCSD/Rady Children’s Hospital of
San Diego
July 8, 2010
Dr. Teresa Mattina

The natural history of Jacobsen syndrome: A
comprehensive analysis of the physical findings
in JS
7th Annual International 11q Conference
San Diego, CA
July, 2010
Management of Behavior Problems in
Children with Developmental Delay
Martin T. Stein MD
Division of Child Development and Community Health
Department of Pediatrics
University of California San Diego
Rady Children’s Hospital
Autism: Separating facts from
myths and what you need to know
about your child
Natacha Akshoomoff, Ph.D.
Department of Psychiatry, University of California, San Diego
Child & Adolescent Services Research Center and
Developmental Services
Rady Children's Hospital, San Diego
Conflict of Interest: None
Jessica Fekete (11q mom)
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Understanding Behavior issues
Endocrine Aspects of 11q
Is there a role for GH?
…no
issue
Thomas G. Kelly, MD, FAAP
Pediatric Endocrinology
UC San Diego / Rady Children’s Hospital San Diego
Dr. Neel Tipnis
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Chronic constipation and other gastrointestinal
problems (A fun and informative discussion
about bowel movements!)
JACOBSEN’S and the
EYE
Music Therapy
7th Annual 11q Conference
MusicWorx Inc.
Bleeding in Paris-Trousseau
syndrome
11q23 Family Conference
July, 2010
Mr. Chuck Hehmeyer, Esq
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Navigating the legal system to get what your 11q
child needs
Clinical Assessments
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1). Dr. Mattina/Dr. Gillgopian (General, as well as
blood draw for high resolution deletion mapping for
those patients that have not yet had this done).
2). Drs. Sarah Mattson/Natacha Akshoomoff
(Cognitive/behavioral): Questionnaires and onsite
testing at SDSU
3). Dr. Zsuzsanna Bata-Csörg: Dermatologist (on site
assessments with Dr. Mattina).
4). Dr. Neil Tipnis (questionnaire???)
PROGRESS
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FOURTEEN papers published since we started
in 1997!!!
But MANY challenges still exist.
You, as parents, have a critical role and
responsibility to help educate others about JS. It
can literally save your child’s life!!!