Gene Discovery for Disease Models

by Gu, Weikuan; Wang, Yongjun

• ISBN13: 9780470499467
• ISBN10: 047049946X
• Edition: 1st
• Format: Hardcover
• Copyright: 2011-05-03
• Publisher: Wiley

Summary

This book provides readers with new paradigms on the mutation discovery in the post-genome era. The completion of human and other genome sequencing, along with other new technologies, such as mutation analysis and microarray, has dramatically accelerated the progress in positional cloning of genes from mutated models. In 2002, the Mouse Genome Sequencing Consortium stated that "The availability of an annotated mouse genome sequence now provides the most efficient tool yet in the gene hunter's toolkit. One can move directly from genetic mapping to identification of candidate genes, and the experimental process is reduced to PCR amplification and sequencing of exons and other conserved elements in the candidate interval. With this streamlined protocol, it is anticipated that many decades-old mouse mutants will be understood precisely at the DNA level in the near future." The implication of such a statement should be similar to the identification of mutated genes from human diseases and animal models, when genome sequencing is completed for them. More than five years have passed, but genes in many human diseases and animal models have not yet been identified. In some cases, the identification of the mutated genes has been a bottleneck, because the genetic mechanism holds the key to understand the basis of the diseases. However, an integrative strategy, which is a combination of genetic mapping, genome resources, bioinformatics tools, and high throughput technologies, has been developed and tested. The classic paradigm of positional cloning has evolved with completely new concepts of genomic cloning and protocols. This book describes new concepts of gene discovery in the post-genome era and the use of streamlined protocols to identify genes of interest. This book helps identify not only large insertions/deletions but also single nucleotide mutations or polymorphisms that regulate quantitative trait loci (QTL).

Author Biography

Weikuan Gu received his PhD from Cornell University in 1994 and joined the University of Tennessee Health Science Center as an assistant professor in 2002. Dr. Gu's lab has developed an integrated strategy for the positional cloning of genes, a strategy which has been successfully applied to clone several genes from spontaneous mouse mutations. Yongjun Wang received his MD from Hebei Medical College in 1982 and his MBA from Peking University in 2004. Dr. Wang joined Beijing Tiantan Hospital in 2000 and now serves as the vice president of the hospital.

Table of Contents

Preface	p. vii
Acknowledgments	p. ix
Contributors	p. xi
Gene Discovery: From Positional Cloning to Genomic Cloning	p. 1
High-Throughput Gene Expression Analysis and the Identification of Expression QTLs	p. 11
DNA Methylation in the Pathogenesis of Autoimmunity	p. 31
Cell-Based Analysis with Microfluidic Chip	p. 59
Missing Dimension: Protein Turnover Rate Measurement in Gene Discovery	p. 83
Bioinformatics Tools for Gene Function Prediction	p. 93
Determination of Genomic Locations of Target Genetic Loci	p. 111
Mutation Discovery Using High-Throughput Mutation Screening Technology	p. 139
Candidate Screening through Gene Expression Profile	p. 165
Candidate Screening through High-Density SNP Array	p. 195
Gene Discovery by Direct Genome Sequencing	p. 215
Candidate Screening through Bioinformatics Tools	p. 235
Using an Integrative Strategy to Identify Mutations	p. 261
Determination of the Function of a Mutation	p. 279
Confirmation of a Mutation by Multiple Molecular Approaches	p. 303
Confirmation of a Mutation by MicroRNA	p. 343
Confirmation of Gene Function Using Translational Approaches	p. 371
Confirmation of Single Nucleotide Mutations	p. 391
Initial Identification and Confirmation of a QTL Gene	p. 403
Gene Discovery of Crop Disease in the Postgenome Era	p. 425
Impact of Genomewide Structural Variation on Gene Discovery	p. 443
Impact of Whole Genome Protein Analysis on Gene Discovery of Disease Models	p. 471
Index	p. 531
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