Discovery of rare ancestry-specific variants in the fetal genome that confer risk of preterm premature rupture of membranes (PPROM) and preterm birth.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth, a complication that is more common in African Americans. Attempts to identify genetic loci associated with preterm birth using genome-wide association studies (GWAS) have only been successful with large numbers of cases and controls, and there has yet to be a convincing genetic association to explain racial/ethnic disparities. Indeed, the search for ancestry-specific variants associated with preterm birth has led to the conclusion that spontaneous preterm birth could be the consequence of multiple rare variants. The hypothesis that preterm birth is due to rare genetic variants that would go undetected in standard GWAS has been explored in the present study. The detection and validation of these rare variants present challenges because of the low allele frequency. However, some success in the identification of fetal loci/genes associated with preterm birth using whole genome sequencing and whole exome sequencing (WES) has recently been reported. While encouraging, this is currently an expensive technology, and methods to leverage the sequencing data to quickly identify and cost-effectively validate variants are needed. METHODS: We developed a WES data analysis strategy based on neonatal genomic DNA from PPROM cases and term controls that was unencumbered by preselection of candidate genes, and capable of identifying variants in African Americans worthy of focused evaluation to establish statistically significant associations. RESULTS: We describe this approach and the identification of damaging nonsense variants of African ancestry in the DEFB1 and MBL2 genes that encode anti-microbial proteins that presumably defend the fetal membranes from infectious agents. Our approach also enabled us to rule out a likely contribution of a predicted damaging nonsense variant in the METTL7B gene. CONCLUSIONS: Our findings support the notion that multiple rare population-specific variants in the fetal genome contribute to preterm birth associated with PPROM.

The significance of cancer stem cells in the diagnosis and treatment of malignant tumor / 国际外科学杂志

Malignant tumors still threatens the human's health seriously. Metastasis and recurrence lead to the failure of treatment, and multidrug resistance adds the difficulty of therapy of to malignant tumors. But the mechanism is yet unclear. Nowadays, it is found that there's a small group of cells with selfrenewal and indefinite potency in the tumors, and they are the sources of metastasis and recurrence. This small group of cells is called cancer stem cells. Subsequently, the cancer stem ceils were separated and determined from hematological system tumor and solid tumor respectively. The cognitions for metastasis and recurrence and muhidrug resistance of malignant tumor have changed with proposal and verification of the cancer stem cell theory, which provides a new clue to the treatment of tumor and prevention for the metastasis and recurrence.

The relationship between the expression of P16 and the prognosis of oesophagus cancer / 中国基层医药

Objective Previons studies showed that,the gene of P16 is a kind of gene suppressing the cancer.its function once lose,the cell may change to cancer.Methods The expression of P16 has a closely relation with the malignant latent and evolve of the oesophagus cancer.ResulIs This research explored the relation between the P16 expression and the prognosis of oesophagus cancer,the results showed the positive rate of the expression of P16 is more low the rate ofexistence is more low,it in dicates the expression rate of P16 can reflect the prognosis of oesophagus cancer cell.Conclusion The expression of P16 missing or descending is closely rehted with the aggravate and evolve of oesophagus cancer,therefore the expression of P16 had a relation with the prognosis of oesophagus cancer.