Genome-wide association analysis reveals novel loci for hypoxia adaptability in Tibetan chicken.

The Tibetan chicken (TBC), an indigenous chicken breed of the Tibetan Plateau, has adapted to its hypoxic, high-altitude environment over hundreds of years. The objective of this study was to identify the polymorphisms and genes associated with adaptation to hypoxia in this chicken breed. In the present study, samples were collected during days 18-21 of the incubation period from both surviving chicks and dead embryos, all of which were hatched under hypoxic conditions. A genome-wide association study was conducted using the Illumina iSelect 60K SNP array with a case-control design, in which the case group consisted of the dead chicken embryos (n = 54) and controls were the surviving chicks (n = 82). Four significant SNPs were detected at the genome-wide level (P < 0.05), and the results indicated that fork head box G1 (FOXG1) was the main candidate gene. The lead SNP NC_006092.4:g.33368893T>C was confirmed with a polymerase chain reaction-restriction fragment length polymorphism analysis of 122 cases and 212 controls. A chi-square test showed a significant association between NC_006092.4:g.33368893T>C and hatchability under hypoxic conditions (P < 0.01). Our results revealed novel polymorphisms and a candidate gene associated with hypoxic adaptation, facilitating further study in this field.

Chondrosarcoma and peroxisome proliferator-activated receptor.

Induction of differentiation and apoptosis in cancer cells by ligands of PPARgamma is a novel therapeutic approach to malignant tumors. Chondrosarcoma (malignant cartilage tumor) and OUMS-27 cells (cell line established from grade III human chondrosarcoma) express PPARgamma. PPARgamma ligands inhibited cell proliferation in a dose-dependent manner, and induced apoptosis of OUMS-27. The higher-grade chondrosarcoma expressed a higher amount of antiapoptotic Bcl-xL in vivo. The treatment of OUMS-27 by 15d-PGJ(2), the most potent endogenous ligand for PPARgamma, downregulated expression of Bcl-xL and induced transient upregulation of proapoptotic Bax, which could accelerate cytochrome c release from mitochondria to the cytosol, followed by induction of caspase-dependent apoptosis. 15d-PGJ(2) induced the expression of CDK inhibitor p21 protein in human chondrosarcoma cells, which appears to be involved in the mechanism of inhibition of cell proliferation. These findings suggest that targeted therapy with PPARgamma ligands could be a novel strategy against chondrosarcoma.