Project description:SUMOylation involves the attachment of Small Ubiquitin-like Modifier (SUMO) proteins to specific lysine residues on thousands of substrates with various effects on protein function. Sentrin-specific proteases (SENPs) are proteins involved in the maturation and de-conjugation of SUMO. Specifically, SENP7 is responsible for processing polySUMO chains on targeted substrates including the heterochromatin protein HP1α. Here, we describe a large family with four affected subjects presenting with a spectrum of findings including congenital arthrogryposis, profound developmental delay, and neutropenia with recurrent infections. Exome sequencing identified a homozygous stop gain variant in SENP7 c.1474C>T; p.(Gln492*) as the probable etiology. Protein expression studies in patient fibroblasts showed significant protein dysregulation in total cell lysates and in the chromatin fraction.
Project description:Purpose: There are three goals of this study: 1. To compare the genomic, exome and chromatin accessiblity profiles of the specific engineered fallopian tube cells of high-grade serous tubo-ovarian cancer (HGSC) models (this study) using whole-exome, whole-genome and ATAC-seq sequencing. Methods: For whole-exome analysis, genomic DNA was extracted from the cell lines mentioned below. Conclusions: We conclude that whole-exome, whole-genome and ATAC-seq characterization would expedite genetic network analyses and permit the dissection of complex biological functions.
Project description:SMARCB1 encodes a core subunit of the SWI/SNF chromatin remodeling complex, which plays a crucial role in the regulation of gene expression. Germline mutations in the SMARCB1 gene have been linked to early childhood Coffin-Siris syndrome type 3 (CSS3), a rare congenital malformation syndrome characterized by severe developmental delay and intellectual disability. In this study, we report two adult CSS3 patients with novel missense SMARCB1 mutation (c.1091A>C, p.Lys364Thr) identified through whole exome sequencing (WES). Both two patients exhibited selective difficulties in verbal learning and language delay. Additionally, the development of meningioma was confirmed in one of the patients. Mechanistic studies indicate that this missense mutation may abnormally activates the expression of MAPK14, a gene implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in SMARCB1 gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related neurodevelopmental disorders.
Project description:Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.
