- 1. Introduction to Genetics and Overview of the Conference Paul
Grossfeld, M.D. Associate Adjunct Professor UCSD School of Medicine
July 7, 2010
2. Highresolutionkaryotype 3. 4. Highresolutionkaryotype
5. FISH Methodology
- Www.nhgri.nih.gov./DIR/VIP(Artist Darryl Leja)
6. 7. FISH Analysis
-
- Microdeletions/Microduplications
-
- 500-600 probes needed to match the power of karyotyping
8. Microdeletion Detection 9. Microdeletion Detection 10. FISH
Analysis 11. To improve detection
- G-banding alone is insufficient to identify clinically
significant deletions/duplications
- Additional molecular cytogenetic technologies are needed that
offer a whole genome approach to submicroscopic imbalances
12. Array-basedC omparativeG enomicH ybridization
- Molecularcytogenetic method to detect copy number
imbalances
- Capable ofgenome widescanning
- Objectivemethod compared to routine cytogenetic G-banding and
FISH analysis
13. 14. Methods
- Isolate Genomic DNA from samples
- Label patient and control samples
- Post hybridization washing
- Assay scanning and data analysis
15. Array Design
- Resolution depends on clone size and spacing
- Only detect unbalanced rearrangements
- Creates a molecular karyotype
16. Indications - Postnatal
- Multiple congenital anomalies
- Developmental delay/ mental retardation of unknown origin
- Any individual suspected of a chromosomal imbalance, even with
normal karyotype
- High resolution mapping to identify specific genes
17. 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
18. 19. Array Formats High Resolution
- 1-3 Mb spacing across the genome
- Oligonucleotides used to cover the genome
- Approximately 50,000 clones
- Numerous polymorphisms identified
20. High Density Oligo CGH 21. Characterization of known
cytogenetic rearrangements to determine size and gene content 22.
Approximately 10% imbalances detected in individuals with normal
karytoype 23. 24. 25. 26. 27. Definition of 11q Terminal Deletion
Disorder
- Either sporadic (normal parents, 90-95%) or inherited (from a
parent with a balanced translocation, 5-10%)
- Can be an Inteial Deletion (very rare)
- NOT aBalanced Translocation/BalancedTranslocation
28. Balanced Translocation 29. Mechanisms of 11q- deletions
- 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
30. Overview of the Conference
31. Dr. Sarah Mattson
- 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
32. Traditional Osteopathic Medicine Kathryn Gill, M.D. 33. The
effects of Neurogranin on learning and memory in 11q-Andras
Bratincsak, MD, PhD July 8 th , 2010 34. The ETS-1 gene and heart
defects in 11q-:Clinical implicationsPaul Grossfeld, M.D. Associate
Adjunct Professor UCSD/Rady Childrens Hospital of San Diego July 8,
2010 35. Dr. Teresa Mattina
- The natural history of Jacobsen syndrome:A comprehensive
analysis of the physical findings in JS
36. 7 thAnnual International 11q Conference San Diego, CAJuly,
2010 Management of Behavior Problems in Children with Developmental
Delay Martin T. Stein MD Division of Child Development and
Community Health Department of PediatricsUniversity of California
San Diego Rady Childrens Hospital 37. 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 38. Jessica Fekete (11q mom)
- Understanding Behavior issues
39. Endocrine Aspects of 11q Is there a role for GH?noissue
Thomas G. Kelly, MD, FAAP Pediatric EndocrinologyUC San Diego /
Rady Childrens Hospital San Diego Small 40. Dr. Neel Tipnis
- Chronic constipation and other gastrointestinal problems (A fun
and informative discussion about bowel movements!)
41. JACOBSENS and the EYE 42. 7 thAnnual 11q Conference
MusicWorx Inc. Music Therapy 43. Bleeding in Paris-Trousseau
syndrome 11q23 Family Conference July, 2010 44. Mr. Chuck Hehmeyer,
Esq
- Navigating the legal system to get what your 11q child
needs
45. Clinical Assessments
- 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-Csrg:Dermatologist (on site assessments
with Dr. Mattina).
- 4). Dr. Neil Tipnis (questionnaire???)
46. PROGRESS
- 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 childs
life!!!