Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.

For gene therapy to be effective in cancers, it is necessary to deliver therapeutic genes into cells with high specificity and efficiency. In this study, we examined the in vitro and in vivo gene delivery efficiency of a new, growth receptor-mediated gene transfer system in hepatocellular carcinoma (HCC). The effects of transfection of wild-type p53 using this system were also studied. The system consisted of a ligand oligopeptide for epidermal growth factor receptor (EGFR) recognition, a polypeptide for DNA binding, and an endosome-releasing oligopeptide for endosomolysis. Two human HCC cell lines and a normal liver cell line were used, and pCMV-␤-galactosidase (␤-gal) was used as a reporter gene. Both HCC cell lines had strong expression of EGFR and the in vitro transfer efficiency peaked at day 5 at about 50%. This finding was in contrast to the normal liver cell line, which had weak EGFR expression and less than 1% transfer efficiency throughout. For in vivo gene transfer in tumors produced by inoculating HCC cells in nude mice and with the vector-␤-gal gene complex injected peritumorally, ␤-gal expression was detected within the tumors at 12 hr, peaked at day 5 involving about 50% of the tumor cells and persisted at 2 weeks. Using this vector system, transfection of wild-type p53 into Huh-7 cells that had mutated p53 resulted in significant growth inhibition of cancer cells accompanied by a decreased G2/M phase and increased p53 protein. In conclusion, this receptor-mediated gene transfer system appears to work specifically in HCC cells with high efficiency, and may be promising in delivering apoptotic and other genes into HCC cells.

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Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2--galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with the * The present receptor-mediated gene delivery system has been patented by Gu and Tian (Patent Registration number in China 96116557 X; PCT/CN 97/00106)