Lecture 30 and 31

Question 1

Dominant trait

Answer 1

effects of a variant allele are observed in the presence of a normal allele (heterozygous)

Question 2

Recessive trait

Answer 2

effects of a variant allele are observed only in the absence of a normal allele (homozygous)

Question 3

Autosomal

Answer 3

chromosomes 1-22

Question 4

Sex-linked

Answer 4

X and Y chromosomes

Question 5

Inheritance of autosomal dominant trait

Answer 5

results in a 50% chance of passing trait to each child

only one parent has mutated gene
Unaffected siblings do not transmit the disorder

Age of onset is delayed for some autosomal dominant diseases don’t see the full effect until later in life

Huntington disease

Question 6

Inheritance of autosomal recessive trait

Answer 6

only sees the trait if both parents have the mutant gene

25% chance of having an affected child
50 % chance carrier child
25% chance non carrier

All child of affected parents are carriers

Age onset is early in life for many conditions because the gene can be passed on through carriers

Symptoms tend to be more uniform

Question 7

Penetrance

Answer 7

some show mutated genes and others do not

Any trait associated with the variant

Complete= 100%
Incomplete= < 100%

Question 8

Expressivity

Answer 8

how a gene expresses itself in an individual person

Number, identity, extent of severity

Ranges from complete to minimal

Affected by other genes, exposure to harmful conditions, environment, age

Question 9

Genetic variant

Answer 9

permanent change in the sequence of the gene

Question 10

Pathogenic variant

Answer 10

change in the sequence of gene responsible for causing the disease

well supported by scientific research

often referred to as mutations

Question 11

Silent mutations

Answer 11

do not have any impact on protein function of the gene

Question 12

Missense mutations

Answer 12

change identity of a single nucleotide, can have more impact on protein function.

Does not have any impact on the nucleotide that is encoded

malfunctioning protein

Question 13

Nonsense mutations

Answer 13

single nucleotide change and changes to a stop codon

causes a shortened or nonfunctional protein to be expressed

Question 14

Likely pathogenic

Answer 14

probably responsible for causing disease

not enough scientific research

Question 15

Uncertain significance

Answer 15

not conformed to cause disease

not enough scientific research

Question 16

Likely benign

Answer 16

probably responsible for causing disease

not enough research to be sure

Question 17

Benign

Answer 17

not responsible for causing disease

strong scientific research to rule out link to disease

Question 18

Insertions

Answer 18

change the number of nucleotides present in the gene

encounter a stop codon

insert 1 or 2 nucleotides can cause a frameshift

Question 19

Deletions

Answer 19

delete a single nucleotide

results in a malfunctioning protein

Question 20

What are the three types of mutations that cause autosomal dominant disorders?

Answer 20

1. Loss of function
2. Gain of function (PCSK9)
3. Dominant negatives: inhibits activity of unmuted copy

Question 21

Which types of mutation cause recessive disorders

Answer 21

Caused by loss of function
- Cystic fibrosis caused by loss-of-function mutations in cystic fibrosis transmembrane conductance regulator
- Unmuted copy is sufficient for functioning
- Most common genetic disease that affects Caucasian populations
- Affects fluid secretions: thickened mucous, pulmonary infections, pancreatic function, bile duct blockage, affects sweat glands

Question 22

X-linked recessive

Answer 22

circle with blue dot= carrier female

daughters are unaffected

affected males pass mutant gene to all daughters

do not pass trait to sons

usually only males are affected

Examples: Hemophilia A and B, G6PD deficiency

Question 23

Karyotype analysis

Answer 23

collect blood cells and halt subdivision in metaphase and they isolate the chromosomes from the cells and stain them (G banding) this is how you diagnose a genetic disease

Question 24

Down syndrome

Answer 24

Trisomy 21: 3 copies instead of 2

• Excessive skin on back of neck
• Transverse palmer crease
• Folded or dysplastic ear
• Mental retardation

Question 25

Triplet repeats mutations

Answer 25

• Some genes repeat 3 nucleotides
• Longer repeats are associated with disruption of gene function
• 40 diseases associated with triplet repeats
• Neurodegeneration diseases
  Passed on from generation, grandchildren are mostly affected

Question 26

Mitochondrial mutations

Answer 26

• Have separate genome that encodes several enzymes involved in oxidative phosphorylation
• Diseases caused by mutations in mitochondrial genes are rare
• Only mother are able to transmit mitochondria
• Daughters, but not sons may transmit mutations

Question 27

Imprinting defects

Answer 27

Parent of origin

Some regions of DNA are turned off in the copy received from the mother or father

occurs in ovum or sperm and is stable

Question 28

Fragile X syndrome

Answer 28

triplet repeat mutation

expands and lengthens over time

elongated face
protruding ears
low muscle tone