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 first life science experiments in ISS: reports of "Rad Gene"-space radiation effects on human cultured cells-

To clarify the biological effects of space environment, especially space radiations, a proposal of "Rad Gene" was performed as the first life science experiment with two human lymphoblastoid cell lines bearing wild-type p53 gene (wtp53) and mutated p53 gene (mp53) in an International Space Station (ISS)for 133 days. We scheduled four projects: (1) DNA damage induced by space radiations including the high linear energy transfer (LET) particles was detected as a track of gamma H2AX foci in the nuclei of these frozen cells. (2) To examine the biological effects of microgravity and space radiations on gene and protein expression of p53-dependent regulated genes, these cells were grown under microgravity and 1 gravity in ISS, and on ground for 8 days and analyzed by DNA and protein arrays. (3) p53-Dependent regulated genes were analyzed in the cultured cells after spaceflight at frozen state exposed to space radiations. (4) To clarify the effects of space radiations on the radio-adaptive response, the space flown cells at frozen state were cultured, and then exposed to challenging X-ray-irradiation. All of the radio-adaptive responses of cell killing, apoptosis, chromosomal aberrations and mutations were found only in wtp53 cells, but not in the mp53 cells

Interstitial chromosomal deletion of the Tsc2 locus is a signature for radiation-associated renal tumors in Eker rats.

Ionizing radiation can damage DNA and thus is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor-suppressor gene Tsc2, are susceptible to radiation-induced renal carcinogenesis. However, the molecular mechanisms involved in Tsc2 inactivation are unclear. We subjected Fischer 344 × Eker (Long Evans Tsc2 ) F1 hybrid rats to gamma-irradiation (2 Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the Tsc2 allele of renal tumors that developed at 1 year after irradiation (N = 24 tumors for GD19, N = 10 for PND5), in comparison with spontaneously developed tumors (N = 8 tumors). Gamma-irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the Tsc2 locus, was 38%, 29%, and 60% in renal carcinomas developed from the nonirradiated, GD19, and PND5 groups, respectively. Array CGH analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation-associated carcinomas. Sequence analysis for the wild-type Tsc2 allele in the LOH-negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base-substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH-negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation-induced cancer risk