Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The complete sequence of human chromosome 5

Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-encoding genes including the protocadherin and interleukin gene families and the first complete versions of each of the large chromosome 5 specific internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders including spinal muscular atrophy (SMA)

Excitation energy deposition and the fission process in the reactions 63Cu + 92,100Mo at 10,17,25 and 35 AMeV 35 and 20Ne + 144,148,154Sm at 20 AMeV

Vita.Excitation energy deposition and light particle emission for fissioning nuclei with excitation energies from 2 to 6 MeV/nucleon are studied for the reaction of 20 AMeV 20Ne with [144,148,154]Sm and 10, 17, 25 and 35 AMeV 63Cu with [92,100]Mo using the Texas A&M Neutron Ball detector. Linear momentum transfers (LMT) are determined from fission fragment folding angle measurements and used to estimate excitation energies. The associated multiplicities of neutrons, protons and a particles are obtained, together with their average energies. These data axe used to reconstruct the initial excitation energies of the compound nucleus. With increasing beam energy, an increasing discrepancy between the excitation energy derived from the LMT measurements and the reconstructed one is observed and attributed to intermediate mass fragment (IMF) emission. The measured neutron multiplicities show a strong increase with increasing neutron to proton ratio of the composite system, as well as increasing beam energy. The experimental data for light particle multiplicities are compared with calculations using the statistical model GEMINI. The effect of the dynamic fission delay on the light particle multiplicities is explored. The neutron multiplicities are relatively insensitive to the dynamic fission delay. The calculated charged particle multiplicities are more sensitive, but the comparisons between the calculation and experiment indicate that the light charged particle multiplicity data are not a good measure of dynamic fission delay

Production workflow tracking and QC analysis

The Joint Genome Institute Production Genomics Facility (PGF) has produced over 2.75 billion bases of draft paired-end sequencing since January 1, 2001. Our sequencing methodologies incorporate two types of DNA template generation: inoculation/SPRI purification and Rolling Circle Amplification (RCA). In order to manage the flow of samples through these processes, a robust database tracking system was developed using ORACLE. Data input and reporting for the workflow has been produced using a combination of commercial database development software and in-house programs. These include ORACLE s WebDB and CGI Perl programming. By leveraging the rapid report and form development cycle using WebDB and augmenting this with the flexibility of in-house programming, we have efficiently deployed a critical laboratory information management system for our data tracking

Production workflow tracking and QC analysis

The Joint Genome Institute Production Genomics Facility (PGF) has produced over 2.75 billion bases of draft paired-end sequencing since January 1, 2001. Our sequencing methodologies incorporate two types of DNA template generation: inoculation/SPRI purification and Rolling Circle Amplification (RCA). In order to manage the flow of samples through these processes, a robust database tracking system was developed using ORACLE. Data input and reporting for the workflow has been produced using a combination of commercial database development software and in-house programs. These include ORACLE s WebDB and CGI Perl programming. By leveraging the rapid report and form development cycle using WebDB and augmenting this with the flexibility of in-house programming, we have efficiently deployed a critical laboratory information management system for our data tracking

Studies in optimal configuration of the LTP

Brightness preservation requirements for ever brighter synchrotron radiation and free electron laser beamlines require surface slope tolerances of x-ray optics on the order of 0.2 mu rad, or better. Hence, the accuracy of dedicated surface slope metrology must be 0.1 mu rad, or even less. Achieving this level of measurement accuracy with the flagship instrument at synchrotron radiation metrology laboratories, the Long Trace Profiler (LTP), requires all significant sources of systematic, random, and instrumental drift errors to be identified, and reduced or eliminated. In this respect, the performance of certain components of the Advanced Light Source LTP-II design [Kirschman, et al., Proc. SPIE, 7077, 70770A-12 (2008)] is analyzed, considering the principal justification for inclusion of each component, possible systematic error due to the quality of its optical material, and drift effects due to generated heat, etc. We investigate the effects of replacement of the existing diode laser with a fiber-coupled laser light source, and demonstrate that reducing the number of components by using a single beam on the surface under test (SUT), rather than an original double beam maintains, or even improves the accuracy of measurement with our LTP. Based on the performance of the upgraded LTP, we trace the further steps for improving of the LTP optical system

Studies in Optimal Configuration of the LTP

Brightness preservation requirements for ever brighter synchrotron radiation and free electron laser beamlines require surface slope tolerances of x-ray optics on the order of 0.2 mu rad, or better. Hence, the accuracy of dedicated surface slope metrology must be 0.1 mu rad, or even less. Achieving this level of measurement accuracy with the flagship instrument at synchrotron radiation metrology laboratories, the Long Trace Profiler (LTP), requires all significant sources of systematic, random, and instrumental drift errors to be identified, and reduced or eliminated. In this respect, the performance of certain components of the Advanced Light Source LTP-II design [Kirschman, et al., Proc. SPIE, 7077, 70770A-12 (2008)] is analyzed, considering the principal justification for inclusion of each component, possible systematic error due to the quality of its optical material, and drift effects due to generated heat, etc. We investigate the effects of replacement of the existing diode laser with a fiber-coupled laser light source, and demonstrate that reducing the number of components by using a single beam on the surface under test (SUT), rather than an original double beam maintains, or even improves the accuracy of measurement with our LTP. Based on the performance of the upgraded LTP, we trace the further steps for improving of the LTP optical system