Chapter 5 Flashcards
What is a nonconservative missense mutation?
Normal AA is replaced with a biochemically AA.
What is an prototypical disease that represents a nonconservative missense mutation?
Sickle Cell Anemia in which the nucleotide repeat CTC is replaced with CAC (glutamic acid-> valine). Cause the RBS to take on a sickle shape.
What is altered in mutations within noncoding sequences?
Can interfere with binding of TFs and thus lead to a reduction in or total lack of transcription. Do not involve exons. Seen in Thalassemias.
What is a prototypical example of a trinucleotide-repeat mutation?
Fragile X-syndrome. There are 250-4000 tandem repeats of the sequence CGG with the FMR1 gene.
What is a distinguishing feature of trinucleotide-repeat mutations?
They are dynamic, meaning that the number of TNR increases during gametogenesis.
Virtually all Mendelian disorders are the result of mutations in what?
Single genes that have large effects.
What is the name of a single mutant gene that may lead to many end effects?
Pleotropism.
What is incomplete penetrance?
Individuals inherit the mutant gene but are phenotypically normal.
What is the name of an allele in which one mutant gene affects the formation of other non-mutant genes?
Dominant Negative
What are some features that distinguish autosomal recessive disorders from sutosomal dominat disorders?
- Expression of defect in more uniform.
- Complete penetrance is common.
- Early onset in life.
What is mainly affected in Autosomal Dominant Disorders?
Enzyme proteins are NOT affected in ADD; instead, receptors and structural proteins are involved.
What is mainly affected in Autosomal Recessive Disorders?
Enzyme proteins are frequently involved.
What are the principal changes seen in Marfan Syndrome?
Changes in the skeleton, eyes, and cardiovascular system.
What is the major way in which Marfan Syndrome is inherited?
Autosomal Dominant.
What is the pathogenesis of Marfan Syndrome?
Inherited defect in an extracellular glycoproteins called Fibrillin-1.
What are the two fundamental mechanisms by which loss of fibrillin leads to leads to the clinical symptoms of Marfan syndrome?
1) Loss of structural support in microfibril rich connective tissue.
2) Excessive activation of TGF-beta signaling.
What is the major mechanism of by which fibrillin protein production is altered in Marfan Syndrome?
Missense mutation in the FBN1 gene that give rise to abnormal fibrillin-1.
What leads to the excessive signaling of TGF-beta in Marfan syndrome?
Loss of microfibrils gives rise to excessive activation of the TGF-beta.
Physically, how do patients with Marfans syndrome present?
Skeletal abnormalities, ocular changes, cardiovascular changes, tall, long exremities, tapering fingers and toes, lax joints, kyphosis, scoliosis, slipping of lumbar vertebral vertebrae, deformed chest.
What cardiovascular changes are seen in Marfans Syndrome?
Mitral valve lesions. Aortic lesions that can lead to aortic dissections that can rupture (majority of deaths due to this).
What is the mainstay treatment for individuals with Marfan syndrome?
Treatment with Beta blockers to reduce the HR and aortic wall stress.
What is the mode of inheritance of Ehlers-Danlos Syndrome?
All three types of Mendelian patterns.
What types of tissues are affected in EDS?
Tissues rich on collagen-> skin, ligaments, and joints.
What is the most common autosomal recessive form of EDS and what is it due to?
Kyphoscoliosis type. Results from mutation in gene coding lysyl hydroxylase, enzyme required for hydroxylatiton of lysine resides in collagen assembly.
What is the cause of the vascular type of EDS?
Abnormality of type 3 collagen due to a mutation affecting the COL3A1 gene.
What is the cause of the arthrochalasia type and dermatosparaxis type of EDS?
Due to defect in the conversion of type 1 procollagen–> collagen.
What is the gene defects in the Vascualr form of EDS?
COL3A1
What is the gene defects the Arthrochalasia type of EDS?
COL1A1 and COL1A2
What is the gene defect in the Dermatosparaxis type of EDS?
Procollagen N-peptidase.
What is a conservative missense mutation?
Point mutation in which the substituted AA is biochemically similar.
