Identification of Somatic Chromosomal Abnormalities in Hypothalamic Hamartoma Tissue at the GLI3 Locus  David W. Craig, Abraham Itty, Corrie Panganiban,

Slides:



Advertisements
Similar presentations
Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.
Advertisements

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.
Clinical Laboratory Analysis of Immunoglobulin Heavy Chain Variable Region Genes for Chronic Lymphocytic Leukemia Prognosis  Philippe Szankasi, David.
Paul J. Norman, Jill A. Hollenbach, Neda Nemat-Gorgani, Wesley M
A Haplotype at STAT2 Introgressed from Neanderthals and Serves as a Candidate of Positive Selection in Papua New Guinea  Fernando L. Mendez, Joseph C.
A Genome-Wide High-Resolution Array-CGH Analysis of Cutaneous Melanoma and Comparison of Array-CGH to FISH in Diagnostic Evaluation  Lu Wang, Mamta Rao,
High-Resolution Genomic Profiling of Disseminated Tumor Cells in Prostate Cancer  Yu Wu, Jamie R. Schoenborn, Colm Morrissey, Jing Xia, Sandy Larson, Lisha.
Hendrikus J. Dubbink, Peggy N. Atmodimedjo, Ronald van Marion, Niels M
Resolving the Breakpoints of the 17q21
Strong Evidence That KIAA0319 on Chromosome 6p Is a Susceptibility Gene for Developmental Dyslexia  Natalie Cope, Denise Harold, Gary Hill, Valentina.
Application of Single-Molecule Amplification and Resequencing Technology for Broad Surveillance of Plasma Mutations in Patients with Advanced Lung Adenocarcinoma 
Application of Single-Molecule Amplification and Resequencing Technology for Broad Surveillance of Plasma Mutations in Patients with Advanced Lung Adenocarcinoma 
Utilization of Whole-Exome Next-Generation Sequencing Variant Read Frequency for Detection of Lesion-Specific, Somatic Loss of Heterozygosity in a Neurofibromatosis.
Genome-wide Profiling in AML Patients Relapsing after Allogeneic Hematopoietic Cell Transplantation  Miguel Waterhouse, Dietmar Pfeifer, Milena Pantic,
Multiplex Pyrosequencing of Two Polymorphisms in DNA Repair Gene XRCC1
Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss  Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,
A Tumor Sorting Protocol that Enables Enrichment of Pancreatic Adenocarcinoma Cells and Facilitation of Genetic Analyses  Zachary S. Boyd, Rajiv Raja,
Reliable Identification of Genomic Variants from RNA-Seq Data
Comparing Algorithms for Genotype Imputation
Newfoundland Rod-Cone Dystrophy, an Early-Onset Retinal Dystrophy, Is Caused by Splice-Junction Mutations in RLBP1  Erica R. Eichers, Jane S. Green, David.
Rapid Molecular Profiling of Myeloproliferative Neoplasms Using Targeted Exon Resequencing of 86 Genes Involved in JAK-STAT Signaling and Epigenetic Regulation 
Microarray Techniques to Analyze Copy-Number Alterations in Genomic DNA: Array Comparative Genomic Hybridization and Single-Nucleotide Polymorphism Array 
A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation  Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.
A Multicolor FISH Assay Does Not Detect DUP25 in Control Individuals or in Reported Positive Control Cells  Yanina Weiland, Jürgen Kraus, Michael R. Speicher 
A Genome-Wide High-Resolution Array-CGH Analysis of Cutaneous Melanoma and Comparison of Array-CGH to FISH in Diagnostic Evaluation  Lu Wang, Mamta Rao,
Clinical Laboratory Analysis of Immunoglobulin Heavy Chain Variable Region Genes for Chronic Lymphocytic Leukemia Prognosis  Philippe Szankasi, David.
Jong-Min Lee, Kyung-Hee Kim, Aram Shin, Michael J
Comprehensive Diagnostic Testing for Stereocilin
Single nucleotide polymorphism array analysis in men with idiopathic azoospermia or oligoasthenozoospermia syndrome  Anne Frühmesser, Ph.D., Peter H.
A Novel Syndrome Combining Thyroid and Neurological Abnormalities Is Associated with Mutations in a Monocarboxylate Transporter Gene  Alexandra M. Dumitrescu,
SNPitty The Journal of Molecular Diagnostics
Weight Loss after Gastric Bypass Is Associated with a Variant at 15q26
Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p  Jaume Mora, Nai-Kong V. Cheung,
SAMS, a Syndrome of Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities Is a Unique Neurocristopathy Caused by Mutations.
AZFc Deletions and Spermatogenic Failure: A Population-Based Survey of 20,000 Y Chromosomes  Steven G. Rozen, Janet D. Marszalek, Kathryn Irenze, Helen.
Microdeletions of 3q29 Confer High Risk for Schizophrenia
Identification of a Novel Risk Locus for Progressive Supranuclear Palsy by a Pooled Genomewide Scan of 500,288 Single-Nucleotide Polymorphisms  Stacey.
High Frequency of Loss of Heterozygosity on Chromosome Region 9p21–p22 but Lack of p16INK4a/p19ARF Mutations in Greek Patients with Basal Cell Carcinoma.
SNP Arrays in Heterogeneous Tissue: Highly Accurate Collection of Both Germline and Somatic Genetic Information from Unpaired Single Tumor Samples  Guillaume.
Mutations in ABCA12 Underlie the Severe Congenital Skin Disease Harlequin Ichthyosis  P. David Kelsell, E. Elizabeth Norgett, Harriet Unsworth, Muy-Teck.
Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation  Janine Wagenstaller, Stephanie.
Haplotypes at ATM Identify Coding-Sequence Variation and Indicate a Region of Extensive Linkage Disequilibrium  Penelope E. Bonnen, Michael D. Story,
A Comprehensive Analysis of Recently Integrated Human Ta L1 Elements
DPY19L2 Deletion as a Major Cause of Globozoospermia
A Three–Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation  David L. Duffy, Grant W. Montgomery, Wei.
Germline Nonsense Mutation and Somatic Inactivation of SMARCA4/BRG1 in a Family with Rhabdoid Tumor Predisposition Syndrome  Reinhard Schneppenheim, Michael.
A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics  Michael Jarvis, Ramaswamy.
E. Wang, Y. -C. Ding, P. Flodman, J. R. Kidd, K. K. Kidd, D. L
Hal M. Hoffman, Fred A. Wright, David H. Broide, Alan A
Allelic Skewing of DNA Methylation Is Widespread across the Genome
Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome
Genotyping of Human Platelet Antigens 1 to 6 and 15 by High-Resolution Amplicon Melting and Conventional Hybridization Probes  Michael Liew, Lesa Nelson,
Using Somatic Mutations from Tumors to Classify Variants in Mismatch Repair Genes  Brian H. Shirts, Eric Q. Konnick, Sarah Upham, Tom Walsh, John Michael.
Jared R. Kohler, David J. Cutler 
A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation  Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.
L-GATOR: Genetic Association Testing for a Longitudinally Measured Quantitative Trait in Samples with Related Individuals  Xiaowei Wu, Mary Sara McPeek 
Trevor J. Pemberton, Chaolong Wang, Jun Z. Li, Noah A. Rosenberg 
Xiang Wan, Can Yang, Qiang Yang, Hong Xue, Xiaodan Fan, Nelson L. S
Xiangfeng Cui, Helen Feiner, Honghua Li 
Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth 
Mutations in HPSE2 Cause Urofacial Syndrome
A Definitive Haplotype Map as Determined by Genotyping Duplicated Haploid Genomes Finds a Predominant Haplotype Preference at Copy-Number Variation Events 
Volume 21, Issue 23, Pages (December 2011)
Evaluating the Effects of Imputation on the Power, Coverage, and Cost Efficiency of Genome-wide SNP Platforms  Carl A. Anderson, Fredrik H. Pettersson,
Kit-Sing Au, Adelaide A. Hebert, E. Steve Roach, Hope Northrup 
A Haplotype at STAT2 Introgressed from Neanderthals and Serves as a Candidate of Positive Selection in Papua New Guinea  Fernando L. Mendez, Joseph C.
Zuoheng Wang, Mary Sara McPeek  The American Journal of Human Genetics 
Development of a Novel Next-Generation Sequencing Assay for Carrier Screening in Old Order Amish and Mennonite Populations of Pennsylvania  Erin L. Crowgey,
High-Resolution Identification of Chromosomal Abnormalities Using Oligonucleotide Arrays Containing 116,204 SNPs  Howard R. Slater, Dione K. Bailey, Hua.
Single nucleotide polymorphism array analysis can distinguish different genetic mechanisms that lead to loss of heterozygosity (LOH). Single nucleotide.
Presentation transcript:

Identification of Somatic Chromosomal Abnormalities in Hypothalamic Hamartoma Tissue at the GLI3 Locus  David W. Craig, Abraham Itty, Corrie Panganiban, Szabolcs Szelinger, Michael C. Kruer, Aswin Sekar, David Reiman, Vinodh Narayanan, Dietrich A. Stephan, John F. Kerrigan  The American Journal of Human Genetics  Volume 82, Issue 2, Pages 366-374 (February 2008) DOI: 10.1016/j.ajhg.2007.10.006 Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 1 Chromosomal Abnormalities on 2020 Blood and tissue pairs were assayed on the Affymetrix 10K platform. Copy-number changes were calculated with the analysis software DChipSNP.19 The amplification was later verified at the GLI3 locus by qPCR. (A) Copy-number analysis indicated that chromosome 7p had a copy number change to 2.5 copies for the tissue and not the blood, whereas all other samples showed no significant stretches of copy-number change. The assay was repeated for verification that the finding was not assay specific. (B) The percent of SNPs receiving a No Call across a 50 SNP window is shown for sample 2020. It would be expected that the No Call rate would increase in a region containing an amplification because SNPs would not easily bin into AA, AB, and BB, as would be the case if the copy number were two or one. Within the 7p region is the GLI3 gene, previously shown to harbor germline mutations causing Pallister Hall syndrome, which is highly associated with HH. The American Journal of Human Genetics 2008 82, 366-374DOI: (10.1016/j.ajhg.2007.10.006) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 2 Observed Loss of Heterozygosity within GLI3 Gene for HH Blood and Tissue Paired Samples LOH was detected either by resequencing, genotyping on the Affymetrix platform, or custom SNP-genotyping with Tm-Shift assays. LOH events were defined as pairs in which the blood sample contained a heterozygous polymorphism (e.g., a heterozygote SNP) and the tissue sample was homozygous. SNPs that were genotyped homozygous in blood were uninformative (shown as gray bars). Samples where a heterozygote was observed in both the tissue and blood samples indicate the absence of LOH. (A) A total of eight samples contained LOH events observed by either genotype data from the Affymetrix 10K GeneChip mapping array (yellow bar), sequencing of a heterozygous SNP within exons (green bar), or SNP genotyping (red bar). Blue bars indicate the nearest flanking SNP to an LOH even (green, yellow, and red bars) where LOH was definitively not observed. Uninformative SNPs that were not within a region of LOH or SNPs that were heterozygous in blood and tissue but did not neighbor an LOH event are not shown, for clarity. (B) Schematic of GLI3 gene aligned to above LOH graphs. (C) Mutations within the GLI3 gene have previously been found to lead to Pallister-Hall Syndrome (PHS). The American Journal of Human Genetics 2008 82, 366-374DOI: (10.1016/j.ajhg.2007.10.006) Copyright © 2008 The American Society of Human Genetics Terms and Conditions