Mutations

Question 2

Mutation

Answer 2

• any change in the DNA sequence of an organism
• source of the altered versions of genes that provide the raw material for evolution
  (only germline mutations are transmitted over generations)
• most cause no affect, are neutral

Question 3

Autosomal recessive inheritance

Answer 3

• associated with Loss of Function mutations
• remember that diploids have two alleles(this means that one allele can still carry the LOF mutation, while the other allele can produce a functional protein product)
• of both alleles are hit with a LOF mutation, this creates a autosomal recessive disease

Question 4

Autosomal dominant inheritance

Answer 4

• associated with Gain of Function mutations
• only ONE allele has to be hit with a GOF mutation in order to develop disease (typically for humans two GOF alleles are embryonically lethal)

Question 5

Autosomal dominant pattern: missense/nonsynonymous/replacement

Answer 5

• A missense/nonsynonymous/replacement mutation leads to a different animo acid in the protein product.

-If the different amino acid causes the protein to function abnormally (e.g. an enzyme with an increased rate), this leads to an autosomal dominant disease.

Question 6

Autosomal dominant inheritance pattern: what causes big increase in quantity of protein produced

Answer 6

• A mutation in a regulatory switch can lead to too much protein produced, protein made in the wrong cell or tissue type, and/or protein produced in the wrong time during ontogeny
• if one GOF allele mutation in regulatory switch, leads to auto. dom. disease

Question 7

Trans-sequence

Answer 7

• sequence change in protein coding DNA sequences

Question 8

Cis regulatory sequence

Answer 8

• sequence change in non-coding regulatory switch DNA sequences

Question 9

Silent mutation

Answer 9

• exon mutation
• base subsitution
• alters no amino acids
• has no effect on protein function

Question 10

Missense

Answer 10

• exon mutation
• base substitution
• alters a nucleotide, which leads to a change of one amino acid
• can be neutral or inhibitory (so a LOF or a GOF)

Question 11

Nonsense

Answer 11

• exon mutation
• base subsitution
• Uracil replaces Thymine for RNA
  -creates a stop codon
• creates short protein
• alters many amino acids, is an ihibitory LOF for proteins

Question 12

Frameshift

Answer 12

• changes multiple amino acids
• creates a addition/deletion mutation in DNA
• exon mutation
• alters many amino acids
• inhibitory LOF on proteins

(exception: insertions and deletions of three will not create a framshift, will be a GOF allele)

Question 13

Sickle Cell Anemia

Answer 13

• missense mutation that creates LOF
• leads to different protein with sickle-like blood cells

Question 14

Cystic Fibrosis

Answer 14

• missing amino acid or defect alters conformation of chloride channels in certain epithelial cell plasma membranes
• water enters cells, drying out secretions
• frequent lung infection, pancreatic insuffciency

Question 15

Duchenne muscular dystrophy

Answer 15

• deletion eliminates dystrophin, which normally binds to inner face of muscle cell plasma membranes, maintaining cellular integrity
• cells and muscles weaken
• gradual loss of muscle function

Question 16

Familial hypercholestolemia

Answer 16

• deficient LDL receptors cause cholesterol to accumulate in the blood
• high blood cholesterol

Question 17

Hemophilia A

Answer 17

• absent or deficient clotting factor causes hard-to-control bleeding
• slow or absent blood clotting

Question 18

Huntington disease

Answer 18

• extra bases in the gene add amino acids to the protein product, which impairs certain transcription factors and proteasomes
• uncontrollable movements

Question 19

Marfan Syndrome

Answer 19

• deficient connective tissue protein in lens and aorta
• long limbs, sunken chest, lens dislocation

Question 20

Neurofibromatosis

Answer 20

• defect in protein that normally suppresses activity of a gene that causes cell division
• benign tumors of nervous tissue beneath skin