A grand summary and synthesis of the tremendous amount of data now available in the post genomic era on the structural features, architecture, and evolution of the human genome. The authors demonstrate how such architectural features may be important to both evolution and to explaining the susceptibility to those DNA rearrangements associated with disease. Technologies to assay for such structural variation of the human genome and to model genomic disorders in mice are also presented. Two appendices detail the genomic disorders, providing genomic features at the locus undergoing rearrangement, their clinical features, and frequency of detection.

A grand summary and synthesis of the tremendous amount of data now available in the post genomic era on the structural features, architecture, and evolution of the human genome. The authors demonstrate how such architectural features may be important to both evolution and to explaining the susceptibility to those DNA rearrangements associated with disease. Technologies to assay for such structural variation of the human genome and to model genomic disorders in mice are also presented. Two appendices detail the genomic disorders, providing genomic features at the locus undergoing rearrangement, their clinical features, and frequency of detection.

Part I. IntroductionThe CMT1A Duplication: A Historical Perspective Viewed From Two Sides of an OceanJames R. Lupski and Vincent TimmermanPart II. Genomic StructureAlu ElementsPrescott DeiningerThe Impact of LINE-1 Retrotransposition on the Human GenomeAmy E. Hulme, Deanna A. Kulpa, José Luis Garcia Perez, and John V. MoranAncient Transposable Elements, Processed Pseudogenes, and Endogenous RetrovirusesAdam Pavlicek and Jerzy JurkaSegmental DuplicationsAndrew J. Sharp and Evan E. EichlerNon-B DNA and Chromosomal RearrangementsAlbino Bacolla and Robert D. WellsGenetic Basis of Olfactory DeficitsIdan Menashe, Ester Feldmesser, and Doron LancetGenomic Organization and Function of Human CentromeresHuntington F. Willard and M. Katharine RuddPart III. Genome EvolutionPrimate Chromosome EvolutionStefan MüllerGenome Plasticity in Evolution: The Centromere RepositioningMariano Rocchi and Nicoletta ArchidiaconoPart IV. Genomic Rearrangements and Disease TraitsThe CMT1A Duplication and HNPP DeletionVincent Timmerman and James R. LupskiSmith-Magenis Syndrome Deletion, Reciprocal Duplication dup(17)(p11.2p11.2), and Other Proximal 17p RearrangementsPawel Stankiewicz, Weimin Bi, and James R. LupskiChromosome 22q11.2 Rearrangement DisordersBernice E. MorrowNeurofibromatosis 1Karen StephensWilliams-Beuren SyndromeStephen W. Scherer and Lucy R. OsborneSotos SyndromeNaohiro Kurotaki and Naomichi MatsumotoX Chromosome RearrangementsPauline H. YenPelizaeus-Merzbacher Disease and Spastic Paraplegia Type 2Ken InoueY-Chromosomal Rearrangements and AzoospermiaMatthew E. Hurles and ChrisTyler-SmithInversion ChromosomesOrsetta Zuffardi, Roberto Ciccone, Sabrina Giglio, and Tiziano PramparoMonosomy 1p36 As a Model for the Molecular Basis of Terminal DeletionsBlake C. Ballif and Lisa G. Shaffer.inv dup(15) and inv dup(22)Heather E. McDermid and Rachel WevrickMechanisms Underlying Neoplasia-Associated Genomic RearrangementsThoas FioretosPart. V. Functional Aspects of Genome StructureRecombination Hotspots in Nonallelic Homologous RecombinationMatthew E. Hurles and James R. LupskiPosition EffectsPawel StankiewiczPart. VI. Genomic Disorders: Modeling and AssaysChromosome-Engineered Mouse ModelsPentao LiuArray-CGH for the Analysis of Consitutional Genomic RearrangementsNigel P. Carter, Heike Fiegler, Susan Gribble, and Richard RedonPart. VII. AppendicesAppendix A: Well-Characterized Rearrangement-Based Diseases and Genome Structural Features at the LocusPawel Stankiewicz and James R. LupskiAppendix B: Diagnostic Potential for Chromosome Microarray AnalysisPawel Stankiewicz, Sau W. Cheung, and Arthur L. BeaudetIndex