Mutational Mechanisms and Disease

Question 1

What are 4 causes of disease due to mutations?

Answer 1

1. loss of function
2. gain of function
3. novel property
4. ectopic or heterochromic expression

Question 2

what occurs to the protein with loss of function?

Answer 2

decreased amount of protein

Question 3

what occurs to the protein with gain of function?

Answer 3

increased amount of protein

Question 4

what occurs in heterochromic expression?

Answer 4

gene is expressed at the wrong time

Question 5

what is the most common genetic mechanism leading to human disease?

Answer 5

loss of function mutation

Question 6

what is the major loss of function mutation in Duchenne Muscular Dystrophy?

Answer 6

frameshift deletions

Question 7

What is the major reduction of function in Becker Muscular dystrophy?

Answer 7

in-frame deletions

Question 8

How does Hereditary neuropathy with liability to pressure palsies form and what type of mutation is it?

Answer 8

deletion of PmP22 gene

loss of function mutation

Question 9

what is the genetic linkage of HNPP (Hereditary neuropathy with liability to pressure palsies)?

Answer 9

autosomal dominant

Question 10

what are allelic disorders?

Answer 10

refer to conditions that are genetically related (due to the same gene most commonly)

Question 11

how are HNPP and CMT1A allelic disorders?

Answer 11

different mutations in the same gene lead to different phenotypes

Question 12

what occurs with ectopic expression?

Answer 12

gene is expressed in the wrong place

Question 13

what occurs in hemoglobin kempsey?

Answer 13

locks hemoglobin in high affinity state thus reducing oxygen delivery to tissues

Question 14

what is the most common way loss of function mutations are inherited to become abnormal phenotypes?

Answer 14

autosomal recessive because need 2 defective genes to display full phenotype

Question 15

what are the causes of duschenne muscular dystrophy?

Answer 15

stop codon, frameshift, or deletion of multiple exons

Question 16

what causes alpha-thalassemia or beta-thalassemia?

Answer 16

deletion of alpha globin or beta globin gene respectively thus reduction in protein causing disease

Question 17

what causes turner syndrome?

Answer 17

loss of entire chromosome (X)

Question 18

what causes hereditary retinoblastoma?

Answer 18

somatic mutation leading to loss of tumor suppressor protein (2nd hit)

Question 19

what is the novel phenotype of osteogenesis imperfecta I?

Answer 19

blue sclera

Question 20

what type of mutation causes osteogenesis imperfecta type I?

Answer 20

premature termination codons (nonsense or frameshift) in COL1A1

Question 21

what is a novel property mutation?

Answer 21

mutation that confer a novel property on a protein without necessarily altering normal functions

Question 22

what are the 2 diseases covered in class that have novel property mutations?

Answer 22

1. sickle cell anemia

2. Huntington disease

Question 23

what is the mechanism of ectopic or heterochronic expression mutations?

Answer 23

mutations that later regulatory regions of a gene and alter either the timing (heterochronic) or location (ectopic) of expression.

Question 24

what are 2 disease examples of ectopic or heterochronic mutations?

Answer 24

1. cancer

2. hereditary persistence of fetal hemoglobin

Question 25

what causes unstable repeat expansions?

Answer 25

slipped mispairing during DNA replication

replicating strand detatches inappropriately and then DNA pol replicates a region in the middle of the gene

Question 26

what is the relationship between repeats and severity of disease?

Answer 26

more repeats leads to more severe disease

Question 27

what process explains genetic anticipation?

Answer 27

tri/tetra nucleotide repeat number expansions occurring from parent to offspring