Project description:The diversity of fin morphology within and across fish taxa offers great, but still largely unexplored, opportunities to investigate the proximate mechanisms underlying fin shape variation. Relying on available genetic knowledge brought forth mainly by the comprehensive study of the zebrafish caudal fin, we explored candidate molecular mechanisms for the maintenance and formation of the conspicuously elongated filaments adorning the unpaired fins of the East African "princess cichlid" Neolamprologus brichardi. Via qPCR assays, we detected expression differences of candidate genes between elongated and short regions of intact and regenerating fins. The identified genes include skeletogenic and growth factors (igf2b, fgf3, bmp2 and bmp4), components of the WNT pathway (lef1, wnt5b and wnt10) and a regulatory network determining fin ray segment size and junction (cx43, esco2 and sema3d), as well as other genes with different roles (mmp9, msxb and pea3). Interestingly, some of these genes showed fin specific expression differences which are often neglected in studies of model fish that focus on the caudal fin. Moreover, while the observed expression patterns were generally consistent with zebrafish results, we also detected deviating expression correlations and gene functions.
Project description:The DNA isolated from 44 either frozen or FFPE Neuroendocrine Neoplasm (NEN) was analysed by NGS, to identify genes more likely to be subject to sequence variations among 523 cancer-related ones.
Project description:Plasma DNA from 558 malignancies, 263 benign and borderline tumors and 367 healthy control samples were collected and subjected to random short-gun whole genome sequencing.
Project description:This study aims to investigate the DNA methylation patterns at transcription factor binding regions and their evolutionary conservation with respect to binding activity divergence. We combined newly generated bisulfite-sequencing experiments in livers of five mammals (human, macaque, mouse, rat and dog) and matched publicly available ChIP-sequencing data for five transcription factors (CEBPA, HNF4a, CTCF, ONECUT1 and FOXA1). To study the chromatin contexts of TF binding subjected to distinct evolutionary pressures, we integrated publicly available active promoter, active enhancer and primed enhancer calls determined by profiling genome wide patterns of H3K27ac, H3K4me3 and H3K4me1.
Project description:Chronic myeloid leukemia (CML) epitomizes successful targeted therapy, with 86% of patients in the chronic phase treated with tyrosine kinase inhibitors (TKIs) attaining remission. However, resistance to TKIs occurs during treatment, and patients with resistance to TKIs progress to the acute phase called Blast Crisis (BC), wherein the survival is restricted to 7-11 months. About 80 % of patients in BC are unresponsive to TKIs. This issue can be addressed by identifying a molecular signature which can predict resistance in CML-CP prior to treatment as well as by delineating the molecular mechanism underlying resistance. Herein, we report genomic analysis of CML patients and imatinib-resistant K562 cell line to achieve the same. WGS was performed on imatinib-sensitive and -resistant K562 cells. Library preparation was done by 30x WGS KAPA PCR-Free v2.1 kit, and Illumina HiSeq X sequencer was used for 2 x 150 bp paired-end sequencing. Our study identified accumulation of aberrations on chromosomes 1, 3, 7, 16 and 22 as predictive of occurrence of resistance. Further, recurrent amplification in chromosomal region 8q11.2-12.1 was detected in highly resistant K562 cells as well as CML patients. The genes present in this region were analyzed to understand molecular mechanism of imatinib resistance.
