SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical...
Transcript of SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical...
![Page 1: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/1.jpg)
SNP OligonucleotideMicoroarray Analysis
(SOMA)in Clinical Cytogenetics
Brynn Levy, M.Sc.(Med)., Ph.D.
![Page 2: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/2.jpg)
• The best whole genome analysis technique currently available is …………………..
GTG-banding of Metaphase chromosomes
Chromosome Analysis
![Page 3: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/3.jpg)
Chromosome Analysis
• G-banding provides a visual examination of the entire genome
• It therefore provides the best coverage but not the best resolution
• Banding resolution differs from preparation to preparation
![Page 4: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/4.jpg)
Diagnostic Limits of Conventional Cytogenetic Analysis
• “Obvious” Aneuploidies & Rearrangements should be easily diagnosed
• The smaller the region of gain/loss, the harder it is to detect
• At Absolute best, imbalances in the realm of 2-5Mb may be detected� Most banding resolutions will allow detection of
gains/deletions of >5Mb
• Absolute best is dependent on banding resolution
![Page 5: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/5.jpg)
How Does Banding Resolution Impact Diagnostic Ability ?
![Page 6: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/6.jpg)
• Small & Subtle aberrations may be missed� Depends on Banding Resolution & Specimen Preparation
• Most clinical labs strive for 550 band level resolution in postnatal studies and greater than 400 bands in prenatal studies. The resolution in bone marrows and products of conception are often at or below the 400 band level
• Make do with what you have and accept the limitations
How Does Banding Resolution Impact Diagnostic Ability ?
![Page 7: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/7.jpg)
Molecular Cytogenetics
• Application of the techniques of Molecular Biology to cytogenetic preparations
• Molecular cytogenetic techniques provide a way to detect complicated, cryptic and submicroscopic rearrangements that remain undetected or undecipherable by conventional cytogenetic analysis
![Page 8: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/8.jpg)
15.3
15.1
14
13.3
13.1
12
11.1
11.2
12
13.1
13.3
14
15
21
22
23.1
23.3
31.1
31.2
31.3
32
33.1
33.3
34
35.1
35.3
15.3
15.1
14
13.3
13.1
12
11.1
11.2
12
13.1
13.3
14
15
21
22
23.1
23.3
31.1
31.2
31.3
32
33.1
33.3
34
35.1
5 add(5)(q35)
Partial Karyotype of Patient
5 add (5)(q35)
![Page 9: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/9.jpg)
wcp 11wcp 5
Chromosome 11
Chromosome 5
![Page 10: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/10.jpg)
Microdeletion Studies Using FISH
Syndrome Chromosome Location Probe/Gene Locus
DiGeorge 22q11.2 D22S75
Velocardiofacial 22q11.2 D22S76
Miller-Dieker 17p13.3 D17S379
Smith-Magenis 17p11.2 D17S29
Prader-Willi 15q11.2 SNRPN
Angelman 15q11.12 D15S10
Williams 7q11.23 Elastin
Cri du chat 5p15.2 D5S23
Wolf-Hirschhorn 4p16.3 D4S96
![Page 11: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/11.jpg)
Prader-WilliSyndrome ??
The Clinical Phenotype Guides the Choice of FISH Test
Williams Syndrome ??
![Page 12: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/12.jpg)
The Clinical Phenotype Guides the Choice of FISH Test
What FISH test do we do in this case ???
![Page 13: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/13.jpg)
Detection of Partial Aneuploidies –An expensive FISHing Expedition
• Unbalanced rearrangements
• Marker chromosomes
• Cryptic translocations
• Cryptic deletions
• Suspected Microdeletions with non-
specific clinical abnormalities
The Need for New TechnologiesThe Need for New TechnologiesThe Need for New TechnologiesThe Need for New Technologies
![Page 14: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/14.jpg)
COMPARATIVE GENOMIC HYBRIDIZATION
C G H
• Identifies chromosomal gains and losses in a
single hybridization procedure
• Effectively reveals any DNA sequence copy number changes (i.e., gains, amplifications, lossesand deletions) in a particular specimen and maps
these changes on normal chromosomes
![Page 15: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/15.jpg)
![Page 16: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/16.jpg)
![Page 17: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/17.jpg)
q21q22
Initial Karyotypic Designation46,XY,t(1;2)(p22;q14.1)
CGH in a patient with an “Apparently Balanced Translocation” and Clinical Abnormalities
2P Telomere
2q Telomere
BAC RPCI-11 91A11
2P Telomere
2q Telomere
BAC RPCI-11 91A11
![Page 18: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/18.jpg)
Interpreting a Normal CGH Result in a Karyotypically Normal Individual with Clinical
Abnormalities
• A normal CGH result has to be interpreted within
the boundaries of the test’s limitations
• A normal CGH result does NOT rule out balanced
cryptic rearrangements
• A normal CGH result does NOT rule out sub-
microscopic imbalances such as microdeletions
![Page 19: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/19.jpg)
Case #: D8 Del 2 M4 M6 D6 D9
Approx. 6-7Mb 14-15Mb 14-16Mb 18-20Mb 9-11Mb 3-4Mb
size of
imbalance
2q+ 2 4 4q- 6 mar 15 mar 22q+ 22 19 mar
![Page 20: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/20.jpg)
CGH IN CLINICAL CYTOGENETICS
• Precise identification of extra or missing material– Important for diagnostic and prognostic value– Important for identifying those genes causative of the
clinical phenotype
• Single step global genome scan preventsFISHing expedition
• DNA based analysis– Quality of patient metaphase spreads is not a consideration
– Non-viable tissues are amenable to analysis
![Page 21: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/21.jpg)
Arrayed clonesArrayed clones
Cloned humanCloned humanDNA (BAC/PAC) DNA (BAC/PAC)
CGH Microarray MethodologyCGH Microarray Methodology
Control genomic Control genomic DNADNA
Test genomic Test genomic DNADNA
Automated Automated analysisanalysis
![Page 22: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/22.jpg)
CGH Microarray MethodologyTrisomy 21 (47,XY,+21)
![Page 23: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/23.jpg)
CGH Microarray Methodology
![Page 24: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/24.jpg)
SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical Cytogenetics – Preliminary Results
• SNP Oligonucleotide microarray for clinical cytogenetic analysis (SOMA)
• With over half a million SNPs and a mean spacing of 5.8 kb, the 500K SNP array offers a comprehensive whole genome scan and has the potential to provide the highest resolution of copy number detection currently available.
• Since deletions and duplications can be precisely defined by using the SNP positions on the genome browser, SOMA will useful for the clinical interpretation of both visible and submicroscopic cytogenetic imbalances.
• Another advantage of using a SNP-based array lies in the concurrent availability of genotype information that would allow simultaneous DNA-based studies such as uniparental disomy (UPD), zygosity and maternal cell contamination.
• Cases were chosen to contain a variety of known cytogenetic aberrations, including whole chromosome aneuploidy, unbalanced rearrangements, marker chromosomes and microdeletions.
• Copy number gains & losses were determined by means of the Circular Binary Segmentation method.
![Page 25: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/25.jpg)
The Use of High Resolution OligonucleotideMicroarray Methodology in Clinical Cytogenetics
Four Important Diagnostic Categories
1. Aneuploidy� Trisomies & Monosomies
2. Partial Aneuploidy at or just below the threshold of the maximum resolution of G-banding (>1-5Mb)
� Unbalanced translocations (of unknown origin)
� Intrachromosomal deletions/duplications
� Marker chromosomes
� Unbalanced “balanced rearrangements”
� Chromosomal rearrangements of indiscernible nature
3. Known Microdeletions/Microduplications (Dynamic list) and Subtelomericimbalances
� Prader-Willi
� DiGeorge
� Cryptic unbalanced translocations
� Terminal Deletions/Duplications
4. Partial Aneuploidies below the resolution of G-banding (<1Mb)� New clinically significant microdeletions/microduplications
![Page 26: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/26.jpg)
Category 1 Cases- Aneuploidy
NormalNoneNone46,XXNormal Reference
Trisomy 21NoneNone47,XX,+21r/o Down Syndrome
NormalNoneNone46,XXNormal Reference
NormalNoneNone46,XYNormal Reference
SOMAAdditional
Study
Results
Workup Additional
KaryotypeIndication
![Page 27: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/27.jpg)
![Page 28: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/28.jpg)
![Page 29: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/29.jpg)
Category 2 Cases - Partial Aneuploidies (>1-5Mb)
![Page 30: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/30.jpg)
47,XX,+r
![Page 31: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/31.jpg)
47,XX,+r
![Page 32: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/32.jpg)
47,XX,+r
![Page 33: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/33.jpg)
![Page 34: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/34.jpg)
Category 2 Cases
8.5
1.8
dim(13)(q14.3q21.2)
dim(13)(q22.1)
dim(13)(q14.3q21.2)
dim(13)(q22.1)ROMA & FISH
46,XY,t(3;10)(q23;q11.2),del(13)
(q14.3q21.2)
Mild Phen
9.4
6.8
2
6.8
11.3
17.3
17.1
15.2
SOMA
Imbalance
(Mb)
enh(15)(q26.1q26.3)enh(15)(q24q26.2)CGH & FISH47,XY,+marSGS
dim(8)(p23.1p23.3)
dim(13)(q11.1q12.11)
enh(8)(p21.2p23.1)
dim(8)(p23.3pter)
dim(13)(q12)
enh(8)(p21p23)
CGH & FISH46,XX,t(8;13)MCA/MR
dim(18)(q12.1q12.3)dim(18)(q12q21)der(18)del(18)(q12q21)t(3;18)(p26;q21.3)
CGH46,XX,t(3;18)MCA/MR
enh(15)(q25.2q26.3)
enh(15)(q25.3q26.3)enh(15)(q24qter)CGH & FISH47,XX,+marSGS (x2)
enh(4)(p12q13.1)enh(4)(p11q13.1)CGH & FISH47,XX,+rMCA/MR
SOMAAdditional
Study Results
Additional
WorkupKaryotypeIndication
![Page 35: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/35.jpg)
Shprintzen-Goldberg Like Phenotype
Patient at age 4½
![Page 36: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/36.jpg)
Cytogenetic Findings
Amniocentesis:
• Revealed mosaicsm for a small marker
chromosome
![Page 37: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/37.jpg)
47,XX,+mar
![Page 38: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/38.jpg)
Molecular Cytogenetic Findings
Postnatal:
• Painting with multiple whole chromosome paints (wcp) revealed the marker to be derived from chr. 15
• PW/AS probe negative� Marker lacks 15 centromeric alpha satellite� Marker does not contain 15q11-q13 region (PW/AS)� Marker does not contain 15q22 region (PML)
• Molecular cytogenetic analysis using Comparative Genomic Hybridization (CGH) showed an overrepresentation of 15q24-qter, consistent with tetrasomy of this region
• Tetrasomy confirmed using a subtelomeric probe for 15q
• The marker was positive for CENP-C indicating the presence of a functional centromere and thus confirming the presence of a neocentromere
![Page 39: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/39.jpg)
wcp 3
wcp 15
![Page 40: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/40.jpg)
![Page 41: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/41.jpg)
Neo 15q – CENP C & Alpha Satellite
![Page 42: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/42.jpg)
15 qtelLSI PML
![Page 43: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/43.jpg)
![Page 44: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/44.jpg)
Category 2 Cases
8.5
1.8
dim(13)(q14.3q21.2)
dim(13)(q22.1)
dim(13)(q14.3q21.2)
dim(13)(q22.1)ROMA & FISH
46,XY,t(3;10)(q23;q11.2),del(13)
(q14.3q21.2)
Mild Phen
9.4
6.8
2
6.8
11.3
17.3
17.1
15.2
SOMA
Imbalance
(Mb)
enh(15)(q26.1q26.3)enh(15)(q24q26.2)CGH & FISH47,XY,+marSGS
dim(8)(p23.1p23.3)
dim(13)(q11.1q12.11)
enh(8)(p21.2p23.1)
dim(8)(p23.3pter)
dim(13)(q12)
enh(8)(p21p23)
CGH & FISH46,XX,t(8;13)MCA/MR
dim(18)(q12.1q12.3)dim(18)(q12q21)der(18)del(18)(q12q21)t(3;18)(p26;q21.3)
CGH46,XX,t(3;18)MCA/MR
enh(15)(q25.2q26.3)
enh(15)(q25.3q26.3)enh(15)(q24qter)CGH & FISH47,XX,+marSGS (x2)
enh(4)(p12q13.1)enh(4)(p11q13.1)CGH & FISH47,XX,+rMCA/MR
SOMAAdditional
Study Results
Additional
WorkupKaryotypeIndication
![Page 45: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/45.jpg)
Neocentric Chr 15FISH the Breakpoints
![Page 46: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/46.jpg)
Balanced t(8;13) ???
![Page 47: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/47.jpg)
![Page 48: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/48.jpg)
![Page 49: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/49.jpg)
8p
8q
CEP 13/21
![Page 50: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/50.jpg)
![Page 51: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/51.jpg)
13 8derivative 8
Proposed Sequence of Events
![Page 52: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/52.jpg)
![Page 53: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/53.jpg)
![Page 54: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/54.jpg)
Category 2 Cases
8.5
1.8
dim(13)(q14.3q21.2)
dim(13)(q22.1)
dim(13)(q14.3q21.2)
dim(13)(q22.1)ROMA & FISH
46,XY,t(3;10)(q23;q11.2),del(13)
(q14.3q21.2)
Mild Phen
9.4
6.8
2
6.8
11.3
17.3
17.1
15.2
SOMA
Imbalance
(Mb)
enh(15)(q26.1q26.3)enh(15)(q24q26.2)CGH & FISH47,XY,+marSGS
dim(8)(p23.1p23.3)
dim(13)(q11.1q12.11)
enh(8)(p21.2p23.1)
dim(8)(p23.3pter)
dim(13)(q12)
enh(8)(p21p23)
CGH & FISH46,XX,t(8;13)MCA/MR
dim(18)(q12.1q12.3)dim(18)(q12q21)der(18)del(18)(q12q21)t(3;18)(p26;q21.3)
CGH46,XX,t(3;18)MCA/MR
enh(15)(q25.2q26.3)
enh(15)(q25.3q26.3)enh(15)(q24qter)CGH & FISH47,XX,+marSGS (x2)
enh(4)(p12q13.1)enh(4)(p11q13.1)CGH & FISH47,XX,+rMCA/MR
SOMAAdditional
Study Results
Additional
WorkupKaryotypeIndication
![Page 55: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/55.jpg)
![Page 56: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/56.jpg)
![Page 57: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/57.jpg)
![Page 58: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/58.jpg)
Category 2 Cases
8.5
1.8
dim(13)(q14.3q21.2)
dim(13)(q22.1)
dim(13)(q14.3q21.2)
dim(13)(q22.1)ROMA & FISH
46,XY,t(3;10)(q23;q11.2),del(13)
(q14.3q21.2)
Mild Phen
9.4
6.8
2
6.8
11.3
17.3
17.1
15.2
SOMA
Imbalance
(Mb)
enh(15)(q26.1q26.3)enh(15)(q24q26.2)CGH & FISH47,XY,+marSGS
dim(8)(p23.1p23.3)
dim(13)(q11.1q12.11)
enh(8)(p21.2p23.1)
dim(8)(p23.3pter)
dim(13)(q12)
enh(8)(p21p23)
CGH & FISH46,XX,t(8;13)MCA/MR
dim(18)(q12.1q12.3)
dim(18)(q12q21)
der(18)del(18)(q12q21)t(3;18)(p26;q21.3)
CGH46,XX,t(3;18)MCA/MR
enh(15)(q25.2q26.3)
enh(15)(q25.3q26.3)enh(15)(q24qter)CGH & FISH47,XX,+marSGS (x2)
enh(4)(p12q13.1)enh(4)(p11q13.1)CGH & FISH47,XX,+rMCA/MR
SOMAAdditional
Study Results
Additional
WorkupKaryotypeIndication
![Page 59: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/59.jpg)
Patient Clinical Info
Delayed major motor milestones, including rolling over at 4 months, sitting without support at 8 months, and walking at 22 months. He had been receiving regular physical therapy for delay in gross motor skills. He spoke in short sentences and understood complex commands. There were no facial dysmorphisms besides slightly cupped ears and no medical problems except for severe eczema.
Normal development status at 3 yrs, except for mild delay in gross motor skills and coordination.
46,XY,t(3;10)(q23;q11.2),del(13)(q14.3q21.2)
![Page 60: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/60.jpg)
N_AB
0
1
2
3
4
5
6
7
0 20000000 40000000 60000000 80000000 100000000 120000000
CNAG 2.0
MSSM
Data AnalysisROMA
![Page 61: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/61.jpg)
Category 2 Cases
8.5
1.8
dim(13)(q14.3q21.2)
dim(13)(q22.1)
dim(13)(q14.3q21.2)
dim(13)(q22.1)ROMA & FISH
46,XY,t(3;10)(q23;q11.2),del(13)
(q14.3q21.2)
Mild Phen
9.4
6.8
2
6.8
11.3
17.3
17.1
15.2
SOMA
Imbalance
(Mb)
enh(15)(q26.1q26.3)enh(15)(q24q26.2)CGH & FISH47,XY,+marSGS
dim(8)(p23.1p23.3)
dim(13)(q11.1q12.11)
enh(8)(p21.2p23.1)
dim(8)(p23.3pter)
dim(13)(q12)
enh(8)(p21p23)
CGH & FISH46,XX,t(8;13)MCA/MR
dim(18)(q12.1q12.3)
dim(18)(q12q21)
der(18)del(18)(q12q21)t(3;18)(
p26;q21.3)CGH46,XX,t(3;18)MCA/MR
enh(15)(q25.2q26.3)
enh(15)(q25.3q26.3)enh(15)(q24qter)CGH & FISH47,XX,+marSGS (x2)
enh(4)(p12q13.1)enh(4)(p11q13.1)CGH & FISH47,XX,+rMCA/MR
SOMAAdditional
Study Results
Additiona
l WorkupKaryotypeIndication
![Page 62: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/62.jpg)
Detailed Examination of Deleted Regions
![Page 63: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/63.jpg)
Category 2 Cases - Cont
0.7dim(15)(q11.2)SNRPN-FISH47,XY,+marSpeech delay
Mild Developmental
delay
7.5
8.4
7.4
19.1
SOMA
Imbalance
(Mb)
dim(2)(q23.1q24.1)dim(2)(q23?q24)CGH & FISHNormalMCA/MR
dim(2)(q23.1q23.3)--46,XX,del(2q37)MCA/MR
dim(11)(p12p14.1)BAC deletionFISH46,XX,del(11p13)Aniridia, MR & ambiguous genetalia
dim(18)(q21.32-18q23)
--del(18q21.32)MCA/MR
SOMA
Additional
Study
Results
Additional
WorkupKaryotypeIndication
![Page 64: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/64.jpg)
Category 2 Cases - Cont
0.7dim(15)(q11.2)SNRPN-FISH47,XY,+marSpeech delay
Mild Developmental
delay
7.5
8.4
7.4
19.1
SOMA
Imbalance
(Mb)
dim(2)(q23.1q24.1)dim(2)(q23?q24)CGH & FISHNormalMCA/MR
dim(2)(q23.1q23.3)--46,XX,del(2q37)MCA/MR
dim(11)(p12p14.1)BAC deletionFISH46,XX,del(11p13)Aniridia, MR & ambiguous genetalia
dim(18)(q21.32-18q23)
--del(18q21.32)MCA/MR
SOMA
Additional
Study
Results
Additional
WorkupKaryotypeIndication
![Page 65: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/65.jpg)
Category 3 Cases
![Page 66: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/66.jpg)
46,XX – Developmental Delay/CHD
46,XX – Developmental Delay/CHD
![Page 67: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/67.jpg)
FISH Using DG Probe
![Page 68: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/68.jpg)
![Page 69: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/69.jpg)
Category 3 Cases
1.0
4.6
2.5
2.5
SOMA
Imbalance
(Mb)
dim(22)(q11.21)dim(22)(q11.2)FISHNormalDiGeorge
dim(4)(p16.2p16.3)WHS x1FISHNormalWHS
dim(9)(q34.3)9qter x 1FISHNormalMCA/MR
dim(22)(q11.21)dim(22)(q11.2)CGH & FISHNormalDiGeorge
SOMAAdditional
Study Results
Additional
WorkupKaryotypeIndication
![Page 70: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/70.jpg)
![Page 71: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/71.jpg)
Category 4 Cases
![Page 72: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/72.jpg)
46,XX,t(11;22)(q23.3;p12)
![Page 73: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/73.jpg)
Molecular Cytogenetic Findings
• CGH analysis normal
• FISH with putative breakpoint gene – normal
• SOMA - dim(20)(q11.22q11.23) – 3.7MB
![Page 74: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/74.jpg)
Category 4 Cases
0.075-0.23
3.7
SOMA
Imbalance
(Mb)
Normal/CNVs/Gene dessertsTUPLE x2
10p probe x2FISHNormalDiGeorge
dim(20)(q11.22q11.23)NormalFISH46,XX,t(11;22)(q23.3;p12)
IUGR, dev delay,
and infantile
spasms
SOMAAdditional
Study
Results
Additional
WorkupKaryotypeIndication
![Page 75: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/75.jpg)
![Page 76: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/76.jpg)
![Page 77: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/77.jpg)
![Page 78: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/78.jpg)
![Page 79: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/79.jpg)
![Page 80: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/80.jpg)
Category 4 Cases
0.075-0.23
3.7
SOMA
Imbalance
(Mb)
Normal/CNVs/Gene desserts
TUPLE x2
10p probe x2FISHNormalDiGeorge
dim(20)(q11.22q11.23)NormalFISH46,XX,t(11;22)(q23.3;p12)
IUGR, dev delay,
and infantile
spasms
SOMAAdditional
Study Results
Additional
WorkupKaryotypeIndication
![Page 81: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/81.jpg)
Oligonucleotide Microarrays
• Oligo Microarrays offer the greatest resolution� Raises the issue of copy number polymorphisms
− Their incidence– De novo versus familial
− Their clinical significance– Pathogenic versus benign variant– Association with disease
• Do they have any influence on the severity of disease
� Future population studies are needed− Ethnic / Race specific
� Improved software for determination of Copy Number− Integration of ongoing data from CNV studies to improve coverage area
![Page 82: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/82.jpg)
Conclusion
• All previously characterized cytogenetic aberrations
could be identified using SOMA
• SOMA fine tunes the breakpoints
• SOMA gives a better assessment of the size of the
imbalance
• The genes involved in the imbalance can be determined
using the SNP positions on the genome browser thus
laying the foundation for more accurate genotype-
phenotype correlations
![Page 83: SNP Oligonucleotide Microarray Analysis (SOMA) in Clinical ...tools.thermofisher.com/content/sfs/brochures/snp_soma_levy.pdf · • Painting with multiple whole chromosome paints](https://reader033.fdocuments.us/reader033/viewer/2022050115/5f4c0503611f322f6853dffc/html5/thumbnails/83.jpg)
AcknowledgementsAcknowledgements
Columbia University Medical Center
• Vaidehi Jobanputra
• Odelia Nahum
• Wendy Chung
• Kwame Anyane-Yeboa
• Dorothy Warburton
Mount Sinai School of Medicine
• Y. Sun
• E. Bottinger
• W. Zhang Columbia UniversityMedical Center