Tuberous Sclerosis (TS) is an autosomal dominant genetic disease characterized by seizures, mental retardation, autism, and benign tumors of the brain, heart, skin, and kidneys. The kidney tumors can also be malignant. This disease exhibits a wide range of severity, and only about 1/3 of the cases are inherited. Two different genes have been tightly linked to the disease in families where it is inherited. The remaining 2/3 appear to be due to mutations in one of the 2 genes as well. Overall it appears that 1/2 are caused by mutations in TSC1 and the other half by mutations in TSC2. A rat model for hereditary renal carcinoma (kidney cancer) has been found. Southern and Northern blot analysis of the TSC1 and TSC2 gene revealed no differences between these rats and normal rats. Not all the rats in the strain would get cancer but a significant proportion did and those were selected for and used in experiments. 1. a) What was detected by the Southern blots? (look this up, make your answer short) b) What was detected by the Northern blots? (look this up, make your answer short) Linkage analysis localized the mutation in rats to the vicinity of a chromosomal region homologous to the human chromosomal region (16p13.3) that contains the TSC2 gene. Sequencing of the TSC2 gene showed a single based insertion in the gene. All of the rats that develop tumors were found to be heterozygous. When mated to each other about 1/3 of their offspring were normal, and 2/3 developed tumors. When the TSC2 gene was examined in the tumor tissue the other copy of the gene had also acquired mutations.
Tuberous Sclerosis (TS) is an autosomal dominant genetic disease characterized by seizures, mental retardation, autism, and benign tumors of the brain, heart, skin, and kidneys. The kidney tumors can also be malignant. This disease exhibits a wide range of severity, and only about 1/3 of the cases are inherited. Two different genes have been tightly linked to the disease in families where it is inherited. The remaining 2/3 appear to be due to mutations in one of the 2 genes as well. Overall it appears that 1/2 are caused by mutations in TSC1 and the other half by mutations in TSC2.
A rat model for hereditary renal carcinoma (kidney cancer) has been found. Southern and Northern blot analysis of the TSC1 and TSC2 gene revealed no differences between these rats and normal rats. Not all the rats in the strain would get cancer but a significant proportion did and those were selected for and used in experiments.
1. a) What was detected by the Southern blots? (look this up, make your answer short)
b) What was detected by the Northern blots? (look this up, make your answer short)
Linkage analysis localized the mutation in rats to the vicinity of a chromosomal region homologous to the human chromosomal region (16p13.3) that contains the TSC2 gene. Sequencing of the TSC2 gene showed a single based insertion in the gene.
All of the rats that develop tumors were found to be heterozygous. When mated to each other about 1/3 of their offspring were normal, and 2/3 developed tumors. When the TSC2 gene was examined in the tumor tissue the other copy of the gene had also acquired mutations.
c) List genetic terms that could be used accurately to describe this gene and the TS disease (other than autosomal dominant). You will lose points for writing anything other than a list here!
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