KTS Syndrome is a genetic disorder clinically characterized by the appearance of
ID: 7899 • Letter: K
Question
KTS Syndrome is a genetic disorder clinically characterized by the appearance of numerous non-cancerous tumors in many organs but particularly in the brain, skin, heart and skeletal muscle. The syndrome is rare affecting only 1 in 6000 individuals and is generally diagnosed after the age of 40 when the tumors become large and obvious. Concurrent with the appearance of the tumors, individuals with this disorder generally display epilepsy, dementia or a combination of both. Patients with KTS syndrome show a range in severity of symptoms. Some have many tumors as well as epilepsy and dementia while others display very few tumors and lead a fairly normal life. The normal protein that is absent or defective in patients is called KTS protein and the gene coding for KTS protein is called the KTS gene.The first complete cDNA clone coding for normal human KTS protein was isolated from a human cDNA library. Since some amino acid sequence data of the KTS protein was available, a degenerate probe was used to screen the library. (Please note - antibodies were not and are now not available for the KTS protein). Following that feat, a genomic clone that codes for the normal KTS gene was isolated. Quite a number of different mutations in the KTS gene of patients with the disorder have been characterized and include base substitutions that result in missence and nonsense codons as well as deletions and insertions that result in frame shifts. Complete nucleotide sequence information of both the human cDNA and human genomic clone has been obtained. The KTS protein is a single polypeptide chain composed of 1164 amino acids.
This is the main question:
In light of the information provided in the text above, how might the scientists have isolated the KTS human genomic clone? Give a brief experimental design.
I simply have no idea
Explanation / Answer
Klippel Trenaunay syndrome (KTS) is a combination on different vascular malformations. It is a syndrome comprised of a lymphatic malformation, port wine stain birthmark, and bony overgrowth.
Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. usage of human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel–Trenaunay syndrome (KTS). One mutation is chromosomal translocation t(5;11), which increases VG5Q transcription. The second is mutation E133K identified in five KTS patients, but not in 200 matched controls. VG5Q protein acts as a potent angiogenic factor in promoting angiogenesis, and suppression of VG5Q expression inhibits vessel formation. E133K is a functional mutation that substantially enhances the angiogenic effect of VG5Q. VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. We also demonstrate a direct interaction of VG5Q with another secreted angiogenic factor, TWEAK (also known as TNFSF12). These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.
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