The finished DNA sequence of human chromosome 12

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.     

The effect of energy feedbacks on continental strength

The classical strength profile of continents is derived from a quasi-static view of their rheological response to stress--one that does not consider dynamic interactions between brittle and ductile layers. Such interactions result in complexities of failure in the brittle-ductile transition and the need to couple energy to understand strain localization. Here we investigate continental deformation by solving the fully coupled energy, momentum and continuum equations. We show that this approach produces unexpected feedback processes, leading to a significantly weaker dynamic strength evolution. In our model, stress localization focused on the brittle-ductile transition leads to the spontaneous development of mid-crustal detachment faults immediately above the strongest crustal layer. We also find that an additional decoupling layer forms between the lower crust and mantle. Our results explain the development of decoupling layers that are observed to accommodate hundreds of kilometres of horizontal motions during continental deformation.     

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.