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The ability to metabolize xenobiotics in organisms has a wide degree of variation among organisms. This is caused by differences in the pattern of xenobiotic bioaccumulation among organisms, which affects their tolerance. It has been reported in the veterinary field that glucuronidation (UGT) activity in cats, acetylation activity in dogs and sulfation (SULT) activity in pigs are sub-vital in these species, respectively, and require close attention when prescribing the medicine. On the other hand, information about species differences in xenobiotics metabolism remains insufficient, especially in non-experimental animals. In the present study, we tried to elucidate xenobiotic metabolism ability, especially in phase II UGT conjugation of various non-experimental animals, by using newly constructed in vivo, in vitro and genomic techniques. The results indicated that marine mammals (Steller sea lion, northern fur seal, and Caspian seal) showed UGT activity as low as that in cats, which was significantly lower than in rats and dogs. Furthermore, UGT1A6 pseudogenes were found in the Steller sea lion and Northern fur seal; all Otariidae species are thought to have the UGT1A6 pseudogene as well. Environmental pollutants and drugs conjugated by UGT are increasing dramatically in the modern world, and their dispersal into the environment can be of great consequence to Carnivora species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds.

Osteoarthritis (OA) is a polygenic disease. Genetic factors are involved in its onset and progression. Identification of its genetic factor, i.e., the susceptibility genes for OA is rapidly in progress by using genomic approaches including genome-wide association study. Recent advance in the study of OA susceptibility genes is reviewed.

Osteoarthritis (OA) is a degenerative disease of articular cartilage. Etiologically, it is classified as primary (idiopathic) and secondary forms. Primary OA is a polygenic disease based on genetic and environmental factors. Identification of its genetic factor, i.e., the susceptibility genes is rapidly in progress. Skeletal dysplasia, inherent failure of formation and/or development of the skeleton, is the frequent cause of secondary OA. Many diseases that belong to skeletal dysplasia, in particular, those which have epiphyseal dysplasia frequently associate OA. Recently, identification of disease genes for skeletal dysplasias is also rapidly in progress. In this paper, I review recent advance in the study of OA susceptibility genes with focus on the relation to disease genes for skeletal dysplasia.

Osteoarthritis (OA) is a polygenic disease based on genetic and environmental factors. Identification of its genetic factor, i.e., the susceptibility genes for OA is rapidly in progress. Recent advance in the study of OA susceptibility genes is reviewed with focus on the genome-wide association study and the large-scale replication study.

Common bone and joint diseases like osteoarthritis and lumbar disc disease are polygenic diseases caused by genetic and environment factors. We are challenging susceptibility genes for common bone and joint diseases using association study as a tool. By a combination of candidate-gene approach and whole-genome screen, we have succeeded in identification of five genes for osteoarthritis and for lumbar disc diseases, respectively. In the present paper, I mention the main genes among them, ASPN, GDF5 and DVWA for osteoarthritis, and TBSP2 and MMP9 for lumbar disc disease. Identification of the new genes will open a new window for the clarification of pathomechanism of the diseases and their treatment.

Recent studies have revealed that the Mycobacterium leprae genome contains many pseudogenes. This short review summarizes the structural features of the M. leprae genome and genes.

Protein S is a plasma glycoprotein, which functions as a cofactor for activated protein C in the protein C pathway and also directly inhibits factors Va and Xa, independently of protein C. In plasma, protein S circulates as a free molecule (40%) or in a complex with C4b-binding protein (60%). Only a free protein S acts as an anticoagulant and its activity is lost by binding to C4b-binding protein. The physiological importance of protein S has been established by observations in patients with hereditary protein S deficiency who have an increased risk of developing thrombosis. Several previous studies reported that hereditary protein S deficiency was as common as protein C deficiency and that approximately 5% of hereditary thrombophilia was caused by protein S deficiency. But molecular biological analysis of protein S deficiency is not as advanced as protein C deficiency because the genetic characterization of protein S deficiency is limited by the presence of the inactive pseudogene that is highly homologous to the active true gene. Only a few previous studies have examined the genetic features of hereditary protein S deficiency. Further investigation is needed to characterize the pathophysiology and molecular basis of hereditary protein S deficiency.