Genetics: Mendelian Inheritance

Question 1

Compound heterozygote

Answer 1

Two different mutant alleles at the same locus

Question 2

Penetrance

Answer 2

Fraction of individuals with a genotype known to cause a disease who have any signs of symptoms of the disease

Question 2

Expressivity (2)

Answer 2

Extent to which a genetic defect is expressed

- Variable expressivity: tray may vary in expression, but it is never completely unexpressed

Question 3

Genetic anticipation + caused by

Answer 3

• The progressively earlier onset and increased severity of certain diseases in successive generations of a family
• Caused by expansion of the number of unstable repeats within the gene responsible for the disease

Question 4

Polygenic inheritance vs. multifactorial inheritance

Answer 4

In multifactorial, environmental as well as genetic factors are involved

Question 5

Polygenic inheritance (3)

Answer 5

• Inheritance determined by many genes at different loci, with small additive effects

Question 6

Proband

Answer 6

Affected family member through whom the family is ascertained

Question 7

Types of inheritance patterns

Answer 7

• Autosomal dominant or recessive
• X linked dominant or recessive
• Y linked

Question 8

Traits of Autosomal dominant inheritance

Answer 8

• Males and females affected
• Successive generations affected; unaffecteds do not transmit
• 1/2 of the offspring at risk are affected
• Male-to-male transmission seen, occurrence and transmission not influenced by gender

Question 9

Autosomal recessive inheritance traits

Answer 9

• Males and females affected
• Single generation affected
• 25% of offspring affected
• Often caused by enzyme deficiencies

Question 10

X-linked dominant inheritance traits

Answer 10

• Both genders are affected by and transmit the disease
• Successive generations are affected
• 50% of offspring of affected females are at risk, all sons of affected males are unaffected, and all daughters of affected males are affected
• No male-to-male transmission of disease

Question 11

Example of X-linked dominant disorder

Answer 11

• Rett syndrome- primarily affects females

Question 12

X-linked recessive inheritance traits

Answer 12

• Males affected, females carriers
• Non-successive generations affected
• 50% of males affected and 50% of females are carriers

Question 13

Y linked inheritance traits

Answer 13

• Males affected
• Males in successive generations affected
• All male offspring of affected males are affected

Question 14

Circumstances under which females can be affected by X-linked recessive disorders: (4)

Answer 14

• Women can be homozygous or compound heterozygous
• De novo mutation
• Skewed X inactivation: if a normal copy of the chromosome X is non-randomly inactivated,, the female carrier is affected

Question 15

Example of codominant inheritance

Answer 15

Blood type

Question 16

Why is inherited breast cancer dominant when one has a back-up normal copy of the BRCA 1 or BRCA 2 gene

Answer 16

• Somatic inactivation of the back up normal copy of hte BRCA 1 gene results in a cell with both BRCA 1 copies inactivated

Question 17

Breast Cancer (4)

Answer 17

• Autosomal dominant
• Incomplete penetrance (not all mutation carriers will develop the disease)
• Locus heterogeneity
• Allelic heterogeneity

Question 18

Hypomorphic allele

Answer 18

Allele with some residual activity

Question 20

Huntington’s disease (3)

Answer 20

• Autosomal dominant
• Triplet repeat expansion
• Genetic anticipation

Question 20

Penetrance vs. variable expressivity

Answer 20

Penetrance is all-or-none
Variable expressivity assumes the person has the symptoms and refers to the variability in the extent to which the person is affected

Question 21

Peroxisome Biogenesis Disorder (7)

Answer 21

• Autosomal recessive
• Missense mutation
• Demonstrates:
  
  • Variable expressivity
  • Pleiotrophy (multiple clinical phenotypes are observed)
  • Locus heterogeneity
  • Allelic heterogeneity
  • Founder Effect

Question 22

Hardy-Weinberg Principle definition

Answer 22

Principle in population genetics that states that genotype frequencies and gene frequencies of a large, randomly mating population remain constant provided immigration, mutation, and selection do not take place

Question 24

Applications of Hardy-Weinberg (2)

Answer 24

• Estimating carrier frequencies of recessive disorders

- Genetic counseling for Mendelian disorders

Question 25

Factors that disrupt Hardy-Weinberg (5)

Answer 25

• Nonrandom mating
• Nonrandom mutation rate
• Strong positive or negative selection
• Small population sizes
• Substantial migration that increases gene flow