Diagnosis of two cases from one family with Joubert syndrome caused by novel mutations of TCTN1 gene by whole exome sequencing / 中华医学遗传学杂志

OBJECTIVE@#To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS).@*METHODS@#Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis.@*RESULTS@#Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins.@*CONCLUSION@#The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.

Gene expression analysis of neoadjuvant chemotherapy efficacy in human breast cancers / 军事医学

Objective To analyze gene expression profiles of biopsy specimens from breast cancer patients who were treated with neoadjuvant chemotherapy(NAC) after biopsies, and to identify the genes which are closely associated with the efficacy of neoadjuvant chemotherapy with T/FAC [docetaxel(Taxotere), 5-fluorouracil, doxorubicin and cyclophosphamide] or T/FEC (Taxotere, 5-fluorouracil, epirubicin and cyclophosphamide) regimen.Methods We retrieved and collected gene expression profiles from publicly available databases.Four datasets, a total of 844 samples, were finally retained because all the patients had received a uniform neoadjuvant chemotherapy regimen.Response to neoadjuvant chemotherapy was categorized as a pathological complete response (pCR) or residual invasive cancer (RD).The differentially expressed genes (adjusted P-value<0.05) and therapeutic efficacy were analyzed and explored.Results After differential analysis, genes whose expressions were higher or lower in pCR group than in RD group were identified in each of the four datasets, respectively.There were 34 and 42 genes which were simultaneously more highly expressed or more lowly expressed in pCR group than in RD group in the four datasets.The unsupervised clustering, based on the 76 intersection genes, showed that the pCR specimens tended to form one cluster and the RD tended to form the other.Conclusion The seventy-six differentially expressed genes are associated with the efficacy of neoadjuvant chemotherapy and are likely to be novel predictive biomarkers for the efficacy of neoadjuvant chemotherapy.

Protein-RNA interactions in Escherichia coli:a genome-wide study / 军事医学

Objective To conduct a pilot study on genome-wide in vivo protein-RNA interactions in E.coli.Methods Bacterial lysate was treated with RNase before the RNA fragments protected by proteins were extracted from treated lysate and used to construct cDNA library that was applied to high-throughput sequencing .Finally, the transcripts bound by proteins were obtained by bioinformatics analysis .Results A total of 3193 transcripts were obtained , including 2234 mRNAs, 47 sRNAs, 39 tRNAs, 11 rRNAs, and 862 intergenic regions .Conclusion Some information of transcripts interacting with proteins in E.coli is acquired , which will facilitate further studies of protein-RNA interactions .