Exome sequencing found a novel homozygous deletion in ADCK3 gene involved in autosomal recessive spinocerebellar ataxia.

Autosomal recessive cerebellar ataxia is heterogeneous inherited neurodegenerative disorders with more than 70 involved genes. The development of next generation sequencing opens a new window in rapid diagnosis of such heterogeneous condition in medical genetics laboratories. Here, we present ADCK3; del.CD (229-230) mutation in an Iranian consanguineous family with three cerebellar ataxic boys using whole exome sequencing. The mutation was predicted pathogenic and all the affected individuals were homozygous for the variant. Although, the ADCK3 was previously reported as one of the master genes of ARSC, our mutation was novel as has been not previously reported in dbSNP or literature.

Identification of a Novel Tumor-Binding Peptide for Lung Cancer Through in-vitro Panning.

Tumor-targeted therapies are playing growing roles in cancer research. The exploitation of these powerful therapeutic modalities largely depends on the discovery of tumor-targeting ligands. Phage display has proven a promising high throughput screening tool for the identification of novel specific peptides with high binding affinity to cancer cells. In the present study, we describe the use of phage display to isolate peptide ligands binding specifically to human lung cancer cells. Towards this goal, we screened a phage display library of 7-mer random peptides in-vitro on non-small cell lung carcinoma (A549) as the target cell. Following selection rounds, there was a highly considerable enrichment of lung cancer-binding phages and a significant increase - 170 fold - of the phage recovery efficiency. After three rounds of in-vitro panning, a group of peptides with different frequencies were obtained. The binding efficiency and selectivity of these peptides for target and control cells were studied. The results of cellular binding assay and cell ELISA (enzyme-linked immunosorbent assay) revealed that LCP1 (Lung Cancer Peptide1) with the displayed sequence AWRTHTP is the most effective peptide in binding to lung cancer cells compared with normal lung epithelial cells and different non-lung tumor cells. In conclusion, our findings suggest that LCP1 may represent a novel peptide that binds specifically to lung cancer cells and further studies can pave the way for its application as a potential targeting moiety in the targeted delivery of diagnostic and therapeutic agents into lung malignant cells.

Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage.

Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer.

Investigation of QF-PCR Application for Rapid Prenatal Diagnosis of Chromosomal Aneuploidies in Iranian Population.

OBJECTIVE: G-Banding followed by standard chromosome analysis is routinely used for prenatal detection of chromosomal abnormalities. In recent years, molecular cytogenetic techniques have been developed for rapid diagnosis of chromosomal abnormalities. Among these methods Quantitative Florescence Polymerase Chain Reaction (QF-PCR) has been widely used for this purpose. Heterozygosity of short tandem repeat (STR) markers which leads to informativity is the most critical requirement for feasibility of QF-PCR. METHODS: In this study we analyzed several short tandem repeats on chromosomes 13, 18, 21, X and Y on amniotic fluid samples obtained from PND candidates to diagnose conditions such as Down, Edward and Patau syndromes and also numerical sex chromosome abnormalities such as Klinefelter and Turner syndromes. FINDINGS: Most of the analyzed STRs had acceptable heterozygosity (66.3-94.7) to be used in QF-PCR based prenatal diagnosis. Moreover, results obtained from both methods (standard karyotype and QF-PCR) for all samples were in accordance with each other. CONCLUSION: In case of using appropriate STR markers, and in certain clinical indications, QF-PCR could be used as useful technique for prenatal diagnosis even in consanguine populations such as Iranians.