SNP in Differentially Methylated Region Upstream of H19 Gene in Guangdong Han Population.

OBJECTIVES: To investigate the single nucleotide polymorphism （SNP） and haplotypes in differentially methylated region （DMR） upstream of H19 gene in Guangdong Han population. METHODS: The PIA typing and restriction enzyme McrBC and HpaⅡ were used to digest the genomic DNA and obtain the individual uniparental DNA template strand. The data of uniparental SNP alleles, genotypes and haplotypes in DMR upstream of H19 gene were obtained by sequencing. RESULTS: A total of 13 SNPs （rs10840167, rs2525883, rs12417375, rs4930101, rs2525882, rs2735970, rs2735971, rs11042170, rs2735972, rs10732516, rs2071094, rs2107425, and rs4930098） and one mutation locus （g7351c） were found. All loci followed the Hardy-Weinberg equilibrium （P>0.05） by statistical analysis. Except for rs12417375 （DP=0.279） locus, the DP of remaining 12 SNPs were 0.446-0.614, and the g7351c mutation locus （DP=0.013） was the particular loci of the Southern Chinese Han population. Eight haplotypes （designated as haplotype 1-8） were detected, in which 3 haplotypes had not yet been reported and the DP, PIC, PE and H were 0.891, 0.714, 0.524 and 0.758, respectively. CONCLUSIONS: Obtained by PIA typing, the SNP in DMR upstream of H19 gene and its haplotypes genetic marker system have a high determination power and show a good practical value in forensic identification.

[Genetic Polymorphisms of SNP Located in the 5' Region of VEGF Gene in Han Population in Guangdong].

OBJECTIVES: To investigate the genetic polymorphism of SNP located in the 5' region of the vascular endothelial growth factor （VEGF） gene in Han population in Guangdong and provide basic data for forensic application and population genetics research. METHODS: The genetic polymorphisms of 4 SNP loci （rs699947, rs1570360, rs833061, rs2010963） within 5' region of VEGF gene of 184 unrelated individuals in Han population in Guangdong were analyzed by DNA micro sequencing technology SNaPshot. The statistical analysis was carried out by PowerMarker v3.25 software. RESULTS: The genotype distributions of the 4 SNP loci within 5' region of VEGF gene of 184 unrelated individuals in Han population in Guangdong were in accordance with Hardy-Weinberg equilibrium （P>0.05） and 3 kinds of genotypes were detected from each loci. There was high linkage disequilibrium between the rs833061 and rs699947 SNP loci. Six haplotypes were observed, while the frequency of C-G-T-C, C-G-T-G, A-A-C-G and A-G-C-G were more than 10%, which were the main haplotypes. The discrimination probabilities （DP） of rs699947, rs833061, and rs2010963 loci were between 0.583 and 0.634, with the power of exclusion （PE） between 0.133 and 0.144. The DP and PE of haplotypes of 4 SNP were 0.868 and 0.438, respectively. CONCLUSIONS: There are great polymorphisms in the 5' region of VEGF gene in Han population in Guangdong, which could be used as genetic indexes for individual identification and paternity testing, as well as association analysis of the related diseases.

Developmental changes in polyamines and autophagic marker levels in normal and growth-restricted fetal pigs.

Polyamines are essential for embryonic and fetal survival, growth, and development. Additionally, polyamines may induce autophagy in mammalian cells. However, little is known about the availability of polyamines or autophagy in the porcine conceptus with intrauterine growth restriction (IUGR). The present study was performed to evaluate the developmental changes of polyamine concentrations in IUGR and normal porcine fetuses as well as autophagic marker levels in the fetal intestinal mucosa during the second half of gestation when most fetal growth occurs. Allantoic fluid (ALF), amniotic fluid (AMF), umbilical vein, and the small-intestinal mucosa were obtained from both IUGR and normal fetal pigs at d 60, 90, and 110 of gestation. Concentrations of polyamines in fetal fluids as well as protein abundances of microtubule-associated protein light chain 3B (LC3B), an autophagic marker, in the fetal small-intestinal mucosa were determined. Concentrations of polyamines varied greatly in different fetal compartments and changed substantially with advancing gestation. Concentrations of polyamines in IUGR fetal fluids and the small-intestinal mucosa were markedly different from those in their normal counterparts at d 60 and 90 of gestation, whereas most of the differences were not detected by late (d 110) gestation. Specifically, polyamine levels were lower in the umbilical vein plasma but higher in ALF and AMF from IUGR fetuses. Furthermore, enhanced levels of an autophagic marker were observed in the small-intestinal mucosa of IUGR fetuses throughout mid and late gestation in association with abnormal spermidine levels in fetal plasma. These findings support the notion that enhanced autophagy may be an important survival mechanism in IUGR fetuses. Collectively, our findings provide a new framework for future studies to define the roles for polyamines in the prevention and treatment of IUGR in both human medicine and animal production.

PI3K pathway alterations in cancer: variations on a theme.

The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors. These recent developments call for a re-evaluation of the oncogenic mechanisms behind PI3K pathway alterations. This pathway is unique in that every major node is frequently mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of PI3K, the p110 alpha catalytic subunit of PI3K, the downstream kinase, AKT, and the negative regulator, PTEN, are all frequently altered in cancer. In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions.