China
Africa
Explore chapters and articles related to this topic
Basic principles in cancer genetics
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
As a result of very careful linkage studies in hereditary cancers, cytogenetic abnormalities in constitutional cells and tumor cells and LOH studies in sporadic tumors, the position of cancer genes was being defined to relatively small regions in the genome. Knowing the position of a gene meant that it was then feasible to isolate it based on this information alone and then to confirm it by demonstrating frequent mutation in patients and tumors with the particular disease. This concept led to the era of ‘positional cloning’ (Collins, 1992) which was the term used to differentiate from functional cloning where the availability of a protein made it possible to use the protein sequence (and hence the mRNA sequence) to identify a cDNA containing the coding sequence. Positional cloning, on the other hand was defined as the identification of a gene based on its chromosomal localization. In this approach, the location of a disease gene was known to within a small (< 1 Mbp) region of the genome. If no obvious candidate gene could be identified in this region, cloning in many cases followed the construction of a contiguous overlapping series of DNA clones which spanned the critical region. This contig then provided the substrate in which to use a variety of approaches such as exon trapping (Auch and Reth, 1990; Buckler et al., 1991) or hybrid cDNA capture (Chen-Liu et al., 1995) to identify potential candidate genes. The traditional cloning vectors used to make human genomic DNA libraries, however, were bacteriophage and cosmids where, although improving the size of the inserts considerably over plasmids, still only offered inserts which were 20–50 Kb. This made building up contigs of overlapping clones very time consuming. Clearly, what was needed was a means of generating large insert clones containing megabases of DNA so that chromosome regions could be spanned with as few clones as possible.
The discovery and development of transmembrane serine protease 2 (TMPRSS2) inhibitors as candidate drugs for the treatment of COVID-19
Published in Expert Opinion on Drug Discovery, 2022
Christiana Mantzourani, Sofia Vasilakaki, Velisaria-Eleni Gerogianni, George Kokotos
One important member of the TTSP subgroup is TMPRSS2, which was first discovered in 1997 by Paoloni-Giacobino et al. using exon-trapping [20]. The TMPRSS2 gene maps to human chromosome 21q22.3 (HC21) and is homologous to the human enteropeptidase gene [21], which also maps to HC21. The TMPRSS2 protein consists of 492 amino acids and it is mainly expressed in the epithelial cells of the prostate, breast, bile duct, kidney, colon, small intestine, pancreas, ovary, salivary gland, stomach, and lung [22]. The structure of this protein is characterized by a 70 amino acid N-terminal cytoplasmic domain, a 36 amino acid transmembrane domain, a class A LDL receptor (LDLRA) domain, a scavenger receptor cysteine-rich (SRCR) domain, and an activation domain linked to a serine protease domain via a disulfide bond (Figure 1(a)) [20].