Chapter 5

Question 1

What is a nonconservative missense mutation?

Answer 1

Normal AA is replaced with a biochemically AA.

Question 2

What is an prototypical disease that represents a nonconservative missense mutation?

Answer 2

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.

Question 3

What is altered in mutations within noncoding sequences?

Answer 3

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.

Question 4

What is a prototypical example of a trinucleotide-repeat mutation?

Answer 4

Fragile X-syndrome. There are 250-4000 tandem repeats of the sequence CGG with the FMR1 gene.

Question 5

What is a distinguishing feature of trinucleotide-repeat mutations?

Answer 5

They are dynamic, meaning that the number of TNR increases during gametogenesis.

Question 6

Virtually all Mendelian disorders are the result of mutations in what?

Answer 6

Single genes that have large effects.

Question 7

What is the name of a single mutant gene that may lead to many end effects?

Answer 7

Pleotropism.

Question 8

What is incomplete penetrance?

Answer 8

Individuals inherit the mutant gene but are phenotypically normal.

Question 9

What is the name of an allele in which one mutant gene affects the formation of other non-mutant genes?

Answer 9

Dominant Negative

Question 10

What are some features that distinguish autosomal recessive disorders from sutosomal dominat disorders?

Answer 10

• Expression of defect in more uniform.
• Complete penetrance is common.
• Early onset in life.

Question 11

What is mainly affected in Autosomal Dominant Disorders?

Answer 11

Enzyme proteins are NOT affected in ADD; instead, receptors and structural proteins are involved.

Question 12

What is mainly affected in Autosomal Recessive Disorders?

Answer 12

Enzyme proteins are frequently involved.

Question 13

What are the principal changes seen in Marfan Syndrome?

Answer 13

Changes in the skeleton, eyes, and cardiovascular system.

Question 14

What is the major way in which Marfan Syndrome is inherited?

Answer 14

Autosomal Dominant.

Question 15

What is the pathogenesis of Marfan Syndrome?

Answer 15

Inherited defect in an extracellular glycoproteins called Fibrillin-1.

Question 16

What are the two fundamental mechanisms by which loss of fibrillin leads to leads to the clinical symptoms of Marfan syndrome?

Answer 16

1) Loss of structural support in microfibril rich connective tissue.
2) Excessive activation of TGF-beta signaling.

Question 17

What is the major mechanism of by which fibrillin protein production is altered in Marfan Syndrome?

Answer 17

Missense mutation in the FBN1 gene that give rise to abnormal fibrillin-1.

Question 18

What leads to the excessive signaling of TGF-beta in Marfan syndrome?

Answer 18

Loss of microfibrils gives rise to excessive activation of the TGF-beta.

Question 19

Physically, how do patients with Marfans syndrome present?

Answer 19

Skeletal abnormalities, ocular changes, cardiovascular changes, tall, long exremities, tapering fingers and toes, lax joints, kyphosis, scoliosis, slipping of lumbar vertebral vertebrae, deformed chest.

Question 20

What cardiovascular changes are seen in Marfans Syndrome?

Answer 20

Mitral valve lesions. Aortic lesions that can lead to aortic dissections that can rupture (majority of deaths due to this).

Question 21

What is the mainstay treatment for individuals with Marfan syndrome?

Answer 21

Treatment with Beta blockers to reduce the HR and aortic wall stress.

Question 22

What is the mode of inheritance of Ehlers-Danlos Syndrome?

Answer 22

All three types of Mendelian patterns.

Question 23

What types of tissues are affected in EDS?

Answer 23

Tissues rich on collagen-> skin, ligaments, and joints.

Question 24

What is the most common autosomal recessive form of EDS and what is it due to?

Answer 24

Kyphoscoliosis type. Results from mutation in gene coding lysyl hydroxylase, enzyme required for hydroxylatiton of lysine resides in collagen assembly.

Question 25

What is the cause of the vascular type of EDS?

Answer 25

Abnormality of type 3 collagen due to a mutation affecting the COL3A1 gene.

Question 26

What is the cause of the arthrochalasia type and dermatosparaxis type of EDS?

Answer 26

Due to defect in the conversion of type 1 procollagen–> collagen.

Question 27

What is the gene defects in the Vascualr form of EDS?

Answer 27

COL3A1

Question 28

What is the gene defects the Arthrochalasia type of EDS?

Answer 28

COL1A1 and COL1A2

Question 29

What is the gene defect in the Dermatosparaxis type of EDS?

Answer 29

Procollagen N-peptidase.

Question 30

What is a conservative missense mutation?

Answer 30

Point mutation in which the substituted AA is biochemically similar.