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Comparative Genomic Hybridization: Current State and Future Directions

Published by: CHI Insight Pharma Reports

Published: Sep. 1, 2006 - 84 Pages


Table of Contents



SECTION 1 CGH Highlights Copy Number Differences

Eclectic Applications

An Overview of the Methodology

The Evolution of CGH




SECTION 2 The Scope of CGH Technology

Methods

Steps

DNA Isolation and Preparation

Amplification

Labeling

Hybridization on a Microarray

Scanning and Analysis

Limitations and Challenges

Underlying Assumptions

Copy Number Polymorphisms (CNPs)

Distinguishing Loss of Heterozygosity

Alternatives to CGH




SECTION 3 Applications of CGH

Reproduction

Assisted Reproduction Technologies

Inherited Developmental Disorders

Mental Retardation

Multifactorial Disorders

Cancer

Evolution




SECTION 4 Expert Interviews

Daniel Pinkel, PhD, University of California, San Francisco,

Comprehensive Cancer Center

Wendy Price, PhD, Invitrogen Corp.

Peggy Eis, NimbleGen Systems Inc.




SECTION 5 Selected Company Profiles

Affymetrix

Agilent

Invitrogen Corp.

Molecular Devices Corp.

NimbleGen Systems Inc.

Signature Genomic Labs, LLC




APPENDIX

CHA Advances: Comparative Genomic Hybridization Survey, August 2006




References




List of Tables and Figures

Figure 1. Outlook for Copy Number Variations in Clinical Testing

Figure 2. Whole-Genome Analysis of a Human Tumor Cell Line

Figure 3. Fine-Tiling Array CGH Analysis

Figure 4. Steps in the CGH Process

Figure 5. Selection of Products and Devices for CGH

Figure 6. GeneChip Human Mapping 500K Array by Affymetrix

Figure 7. SNP vs. CNP, Simplified

Figure 8. Showing LOH Using BeadStudio

Figure 9. Showing a Duplication Using Genome Viewer

Figure 10. Types of Cancer Analyzed Using CGH

Table 1. Selected Acquisitions

Table 2. Selected Amplification Protocols Used in CGH Techniques

Table 3. Selected Genomic Regions Interrogated with CGH

Table 4. Selected Duplication/Deletion Disorders Detected with CGH at Baylor

Abstract

If you’ve not yet heard of Comparative Genomic Hybridization (CGH), you will soon. This fast growing technique for analyzing genomic information by focusing on the differences in the number of sequence copies is firmly established in basic research and is making swift inroads into the clinic. Peggy Eis, PhD, director of the array CGH business at NimbleGen contends that “Information from SNPs is not the only way to look at the genome.” Copy Number Polymorphisms (CNPs) will become a valuable tool for defining relative phenotypes in a population. CGH will eventually play a significant role in the $10 billion molecular diagnostics market, not least in tracking the pathogenesis of, and detecting and monitoring cancer.

Comparative Genomic Hybridization: Current State and Future Directions explains the technology, assesses its limitations and challenges, compares it to prevailing analytical approaches, and examines CGH’s current and impending applications in human health care. Among the findings in this report:

CGH is well positioned, particularly in view of some recent acquisitions, to dominate the $1.5 billion cytogenetics market, including conventional chromosome banding and FISH.
  • CGH’s first health care applications are in assisted reproductive technologies, prenatal diagnosis, and diagnosing inherited developmental disorders. Combimatrix will offer molecular diagnostic tests for mental retardation that incorporate CGH and gene expression profiling.
  • As its precision and reliability are proven, CGH will make further inroads into the clinic. For instance, it will provide clinicians with a way to stratify cancers, revealing distinct subgroups based on CGH pattern ¯ a first step toward personalized medicine.
  • There has been considerable recent growth in model organism CGH ¯ identifying knockouts, mapping the deletion mutants, and using CGH to home in.
A survey (N=66) conducted by CHA in August 2006 of individuals involved with CGH at biopharmaceutical and diagnostic firms, vendors of equipment and services, and academic research departments sheds light on current practices and future directions in the use of CGH in pharmaceutical R&D. Among the highlights:
  • Cancer leads all other CGH applications in both basic research and in the clinic
  • 94% of respondents believe that CGH will become a routine part of clinical testing within the next 5 years, with 42% predicting a 2-year time frame.
A surge in the use of CGH will not only benefit life science researchers - it will also provide tool vendors with an opportunity to sell specialized arrays and other technologies for whole genome profiling. Comparative Genomic Hybridization: Current State and Future Directions profiles the major vendors and their CGH product offerings. The report concludes with in-depth interviews with experts in industry and academia, providing authoritative insight into the scientific, medical, and commercial aspects of CGH.

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