Mechanisms for Nonrecurrent Genomic Rearrangements Associated with CMT1A or HNPP: Rare CNVs as a Cause for Missing Heritability Feng Zhang, Pavel Seeman,

Slides:

Advertisements

Similar presentations

Recurrent Reciprocal Genomic Rearrangements of 17q12 Are Associated with Renal Disease, Diabetes, and Epilepsy Heather C. Mefford, Séverine Clauin, Andrew.

Advertisements

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,

Integrated Cytogenetic and High-Resolution Array CGH Analysis of Genomic Alterations Associated with MYCN Amplification Cytogenet Genome Res 2011;134:27–39.

Human Meiotic Recombination Products Revealed by Sequencing a Hotspot for Homologous Strand Exchange in Multiple HNPP Deletion Patients Lawrence T. Reiter,

The array comparative genomic hybridization (aCGH/CMA) technology

Whole-Genome Scanning by Array Comparative Genomic Hybridization as a Clinical Tool for Risk Assessment in Chronic Lymphocytic Leukemia Shelly R. Gunn,

Recurrent Distal 7q11.23 Deletion Including HIP1 and YWHAG Identified in Patients with Intellectual Disabilities, Epilepsy, and Neurobehavioral Problems

Frequency of Nonallelic Homologous Recombination Is Correlated with Length of Homology: Evidence that Ectopic Synapsis Precedes Ectopic Crossing-Over

Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome Bo.

Tracy I. George, Joanna E. Wrede, Charles D. Bangs, Athena M

Microarray-Based Comparative Genomic Hybridization Using Sex-Matched Reference DNA Provides Greater Sensitivity for Detection of Sex Chromosome Imbalances.

Characterization of Potocki-Lupski Syndrome (dup(17)(p11. 2p11

Resolving the Breakpoints of the 17q21

Zoran Brkanac, Jannine D. Cody, Robin J. Leach, Barbara R. DuPont

Diagnostic Genome Profiling in Mental Retardation

Comparative Genomic Hybridization Analysis of Astrocytomas

Whole-Genome Scanning by Array Comparative Genomic Hybridization as a Clinical Tool for Risk Assessment in Chronic Lymphocytic Leukemia Shelly R. Gunn,

Reciprocal Crossovers and a Positional Preference for Strand Exchange in Recombination Events Resulting in Deletion or Duplication of Chromosome 17p11.2

High-Resolution Mapping of Genotype-Phenotype Relationships in Cri du Chat Syndrome Using Array Comparative Genomic Hybridization Xiaoxiao Zhang, Antoine.

Recombination between Palindromes P5 and P1 on the Human Y Chromosome Causes Massive Deletions and Spermatogenic Failure Sjoerd Repping, Helen Skaletsky,

Genomic Rearrangements Resulting in PLP1 Deletion Occur by Nonhomologous End Joining and Cause Different Dysmyelinating Phenotypes in Males and Females

The Fine-Scale and Complex Architecture of Human Copy-Number Variation

Autosomal-Dominant Microtia Linked to Five Tandem Copies of a Copy-Number- Variable Region at Chromosome 4p16 Irina Balikova, Kevin Martens, Cindy Melotte,

Molecular Characterization and Gene Content of Breakpoint Boundaries in Patients with Neurofibromatosis Type 1 with 17q11.2 Microdeletions Dieter E.

Molecular Cytogenetic Evidence for a Common Breakpoint in the Largest Inverted Duplications of Chromosome 15 A.E. Wandstrat, J. Leana-Cox, L. Jenkins,

Volume 168, Issue 5, Pages e7 (February 2017)

A Multicolor FISH Assay Does Not Detect DUP25 in Control Individuals or in Reported Positive Control Cells Yanina Weiland, Jürgen Kraus, Michael R. Speicher

Genome-wide Transcriptome Profiling Reveals the Functional Impact of Rare De Novo and Recurrent CNVs in Autism Spectrum Disorders Rui Luo, Stephan J.

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,

Claudia M. B. Carvalho, Rolph Pfundt, Daniel A. King, Sarah J

Characterization of Potocki-Lupski Syndrome (dup(17)(p11. 2p11

Kristina Allen-Brady, Peggy A. Norton, James M

Recurrent 10q22-q23 Deletions: A Genomic Disorder on 10q Associated with Cognitive and Behavioral Abnormalities Jorune Balciuniene, Ningping Feng, Kelly.

Mechanism, Prevalence, and More Severe Neuropathy Phenotype of the Charcot- Marie-Tooth Type 1A Triplication Pengfei Liu, Violet Gelowani, Feng Zhang,

Linkage Disequilibrium and Heritability of Copy-Number Polymorphisms within Duplicated Regions of the Human Genome Devin P. Locke, Andrew J. Sharp, Steven.

Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome Bo.

Recurrent Reciprocal Genomic Rearrangements of 17q12 Are Associated with Renal Disease, Diabetes, and Epilepsy Heather C. Mefford, Séverine Clauin, Andrew.

Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion Zhengrui Xi, Lorne Zinman, Danielle Moreno, Jennifer Schymick,

X-Linked Congenital Hypertrichosis Syndrome Is Associated with Interchromosomal Insertions Mediated by a Human-Specific Palindrome near SOX3 Hongwen.

Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation Janine Wagenstaller, Stephanie.

Disruption of Contactin 4 (CNTN4) Results in Developmental Delay and Other Features of 3p Deletion Syndrome Thomas Fernandez, Thomas Morgan, Nicole Davis,

High-Resolution Molecular Characterization of 15q11-q13 Rearrangements by Array Comparative Genomic Hybridization (Array CGH) with Detection of Gene Dosage

A DNA Replication Mechanism for Generating Nonrecurrent Rearrangements Associated with Genomic Disorders Jennifer A. Lee, Claudia M.B. Carvalho, James.

Describing Sequencing Results of Structural Chromosome Rearrangements with a Suggested Next-Generation Cytogenetic Nomenclature Zehra Ordulu, Kristen E.

Copy-Number Gains of HUWE1 Due to Replication- and Recombination-Based Rearrangements Guy Froyen, Stefanie Belet, Francisco Martinez, Cíntia Barros Santos-Rebouças,

Reciprocal Crossovers and a Positional Preference for Strand Exchange in Recombination Events Resulting in Deletion or Duplication of Chromosome 17p11.2

Contribution of SHANK3 Mutations to Autism Spectrum Disorder

The Alu-Rich Genomic Architecture of SPAST Predisposes to Diverse and Functionally Distinct Disease-Associated CNV Alleles Philip M. Boone, Bo Yuan,

Volume 64, Issue 5, Pages (November 2003)

Janet M. Young, RaeLynn M. Endicott, Sean S

Complete Haplotype Sequence of the Human Immunoglobulin Heavy-Chain Variable, Diversity, and Joining Genes and Characterization of Allelic and Copy-Number.

Large Clinically Consequential Imbalances Detected at the Breakpoints of Apparently Balanced and Inherited Chromosome Rearrangements Sarah T. South,

Jennifer A. Lee, James R. Lupski Neuron

DVL3 Alleles Resulting in a −1 Frameshift of the Last Exon Mediate Autosomal- Dominant Robinow Syndrome Janson J. White, Juliana F. Mazzeu, Alexander.

Molecular Analysis of a Deletion Hotspot in the NRXN1 Region Reveals the Involvement of Short Inverted Repeats in Deletion CNVs Xiaoli Chen, Yiping Shen,

The Variant inv(2)(p11.2q13) Is a Genuinely Recurrent Rearrangement but Displays Some Breakpoint Heterogeneity Ina Fickelscher, Thomas Liehr, Kathryn.

Dosage-Dependent Severity of the Phenotype in Patients with Mental Retardation Due to a Recurrent Copy-Number Gain at Xq28 Mediated by an Unusual Recombination

DNA Rearrangements on Both Homologues of Chromosome 17 in a Mildly Delayed Individual with a Family History of Autosomal Dominant Carpal Tunnel Syndrome

2012 William Allan Award: Adventures in Cytogenetics1

Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci Eilis Hannon, Mike Weedon, Nicholas Bray,

Chromothripsis in Healthy Individuals Affects Multiple Protein-Coding Genes and Can Result in Severe Congenital Abnormalities in Offspring Mirjam S.

Exon Array CGH: Detection of Copy-Number Changes at the Resolution of Individual Exons in the Human Genome Pawandeep Dhami, Alison J. Coffey, Stephen.

Annabel C. Whibley, Vincent Plagnol, Patrick S

Harrison Brand, Ryan L. Collins, Carrie Hanscom, Jill A

C. E. Browne, N. R. Dennis, E. Maher, F. L. Long, J. C. Nicholson, J

Anupama Srinivasan, Diana W. Bianchi, Hui Huang, Amy J

Dosage Changes of a Segment at 17p13

Next-Generation Sequencing of Duplication CNVs Reveals that Most Are Tandem and Some Create Fusion Genes at Breakpoints Scott Newman, Karen E. Hermetz,

High-Resolution Identification of Chromosomal Abnormalities Using Oligonucleotide Arrays Containing 116,204 SNPs Howard R. Slater, Dione K. Bailey, Hua.

The Breakpoint Region of the Most Common Isochromosome, i(17q), in Human Neoplasia Is Characterized by a Complex Genomic Architecture with Large, Palindromic,

Presentation transcript:

Mechanisms for Nonrecurrent Genomic Rearrangements Associated with CMT1A or HNPP: Rare CNVs as a Cause for Missing Heritability Feng Zhang, Pavel Seeman, Pengfei Liu, Marian A.J. Weterman, Claudia Gonzaga-Jauregui, Charles F. Towne, Sat Dev Batish, Els De Vriendt, Peter De Jonghe, Bernd Rautenstrauss, Klaus-Henning Krause, Mehrdad Khajavi, Jan Posadka, Antoon Vandenberghe, Francesc Palau, Lionel Van Maldergem, Frank Baas, Vincent Timmerman, James R. Lupski The American Journal of Human Genetics Volume 86, Issue 6, Pages 892-903 (June 2010) DOI: 10.1016/j.ajhg.2010.05.001 Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 1 Oligonucleotide aCGH Analysis of Simple Nonrecurrent Genomic Rearrangements of 17p12 Associated with CMT1A or HNPP Above, for reference, is a horizontal line showing the 1.4 Mb common CMT1A- or HNPP-associated rearrangement region and its flanking sequences on human chromosome 17 with cytogenetic bands depicted above and Megabase (Mb) genomic coordinates (NCBI build 36) below. Locations of the PMP22 gene, the distal and proximal CMT1A-REPs, and LCR17pA are shown. The black horizontal bar shows the location and size of common recurrent 17p12 rearrangements (both deletion and duplication) associated with CMT1A or HNPP. To the left are laboratory identification numbers of the subjects with nonrecurrent 17p12 rearrangements. The green (loss), black (no change), and red (gain) dots show the relative intensities (deviation from the horizontal line of log2Ratio = zero) and genomic locations of the oligonucleotide probes employed in our aCGH assay. The regions that lack unique probes correspond to the LCRs. The regions with copy number gains are indicated in red horizontal bars, and the losses are shown in green. Related subjects: deletions B273.1 and B273.2; duplications C3159 and C4316. The blue vertical lines indicate the location of the PMP22 gene. The arrow indicates the copy number change caused by known polymorphism in the control DNA (NA15510). The American Journal of Human Genetics 2010 86, 892-903DOI: (10.1016/j.ajhg.2010.05.001) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 2 CMT1A-Associated 17p12 Duplications Exclusive of the PMP22 Coding Region but Involving the Potential Upstream Regulatory Sequence (A) Two duplications (red bars) of the upstream region of PMP22 were identified in subject SPR1 and related subjects SD11 and SD14. The SRO involves the TEKT3 and CDRT4 genes, whereas PMP22 is intact and has normal copy number. Both the noncoding exons (1A and 1B) and coding exons (2 to 5) are shown. Three ultra CNSs associated with conserved human transcription factor binding sites were present in SRO. (B) The information of CNS size, lod score, and transcription factor binding site was provided. Details are provided in Figures S2 and S3. The American Journal of Human Genetics 2010 86, 892-903DOI: (10.1016/j.ajhg.2010.05.001) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 3 Oligonucleotide aCGH Analysis Revealed Complex Genomic Rearrangements in 17p12 (A) Subjects C1292 and C2405 are related (C2405 is the sister of C1292's maternal grandfather). Two proposed FoSTeS events (FoSTeS × 2) consistent with this complex rearrangement were shown. (B) In C3011, the 17p CGH array (4 × 44k format) revealed additional duplications in 17p11.2 that is not covered by the CMT1A array (8 × 15k format). Rearrangement abbreviations: nml, normal; dup, duplication. This complex rearrangement can be alternatively interpreted as duplication-normal-duplication-normal-duplication or duplication-normal-duplication that is accompanied by an inversion polymorphism mediated by NAHR between two inverted LCRs (distal and proximal SMS-REPs). The American Journal of Human Genetics 2010 86, 892-903DOI: (10.1016/j.ajhg.2010.05.001) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 4 Oligonucleotide aCGH Analysis of Exonic Rearrangements of PMP22 The deleted regions are shadowed. Below, the locations of the PMP22 gene and its coding exons (2 to 5) are shown. Exon 4 is deleted in subject SPR2. Both subjects A23 and A29 have deletions of exons 1–3. The American Journal of Human Genetics 2010 86, 892-903DOI: (10.1016/j.ajhg.2010.05.001) Copyright © 2010 The American Society of Human Genetics Terms and Conditions