"The last years have seen an extraordinary explosion of studies characterizing genome variation at different levels, and have opened new opportunities in deciphering the genetic basis of phenotypic characteristics and the evolutionary forces involved. One of the major breakthroughs has been the discovery of an unprecedented degree of structural variation in the human genome, including deletions, duplications and inversions. However, the main challenge is to understand the biological significance of these genomic changes. In particular, for many years inversions have been the paradigm of evolutionary biology. Thus, the identification of the whole set of human inversions gives us a unique opportunity to investigate the functional and evolutionary consequences of this type of changes at a large scale. The specific objectives of the project are: (1) Catalogue the precise location of all common polymorphic inversions in the human genome; (2) Determine the population distribution and the evolutionary history of these inversions; (3) Investigate the functional consequences and the effects on gene expression of human inversions; and (4) Assess the effect of inversions on nucleotide variation patterns and the role of natural selection in their maintenance. This project will follow a multidisciplinary approach that combines experimental and bioinformatic analyses and will benefit from the great amount of information on the human genome already available and that will be generated in the next months. The proposed research therefore represents a very appropriate and timely contribution to the study of human structural variation and its role in phenotypic variation and evolution. Furthermore, it will provide additional insights on genome function, gene-expression regulation mechanisms, and the association of genetic changes and particular traits, and promises to stir novel hypothesis for future studies."