Patterns of Inheritance, Pedigree Analysis, and Probabilities

Question 1

autosomal dominant

Answer 1

• recurrence risk in offspring of an affected individual if 50%

Question 2

autosomal dominant pedigree

Answer 2

• phenotype passed from generation to generation
• each affected individuals has a 50% chance of passing allele to child
• multiple generations
• male to male transmission
• males and females equally likely to be affected

Question 3

examples of autosomal dominant conditions

Answer 3

• neurofibromatosis types 1 and 2
• huntington’s disease
• familial breast cancer due to BRCA1 mutation

Question 4

neurofibromatosis type I

Answer 4

• 50% new mutations
• markedly variable expression
• age related penetrance

Question 5

incomplete penetrance

Answer 5

• not every individual is affected

Question 6

mosaicism

Answer 6

• first individual may be mosaic

- spotty

Question 7

exceptions to typical pattern

Answer 7

• de novo mutations

- often associated with advanced paternal age

Question 8

examples of exception to typical pattern

Answer 8

• marfan syndrome - 25% due to de novo mutations
• neurofibromatosis type I - 50% due to de novo mutations
• achondroplasia - 80% due to de novo mutations

Question 9

autosomal recessive

Answer 9

• both parents are carriers
• recurrence risk for siblings is 25%
• very rare disorders - increased risk of consanguinity
• unaffected siblings have 2/3 chance to be carrier

Question 10

autosomal recessive pedigree

Answer 10

• affected individuals usually in one generation

- males and females equally likely affected

Question 11

examples of autosomal recessive conditions

Answer 11

• sickle cell disease
• cystic fibrosis
• PKU
• other metabolic disorders

Question 12

x linked recessive inheritance carrier mother

Answer 12

• 25% that a child will be affected
• 50% chance that a son will be affected
• 50% chance a daughter will be a carrier

Question 13

x inactivation

Answer 13

• one X chromosome in each cell of female is inactivated
• lyon hypothesis
• random but not always 50:50

Question 14

barr body

Answer 14

• inactive X chromosome

Question 15

x linked recessive pedigree

Answer 15

• mother to son transmission
• affected brothers to carrier females
• no male to male transmission
• all daughters of affected males are carriers

Question 16

examples of x linked conditions

Answer 16

• Duchenne muscular dystrophy
• hemophilia A and B
• rickets
• incontinentia pigmenti

Question 17

mitochondrial inheritance

Answer 17

• mitochondrial genome is maternally inherited

Question 18

homoplasmy

Answer 18

• variant present in all mitochondria in an individual

Question 19

heteroplasmy

Answer 19

• variant present in some fraction of mitochondria

Question 20

mitochondrial disorders

Answer 20

• affect organs that require a lot of energy
• MELAS
• Leber’s hereditary optic neuropathy

Question 21

mitochondrial inheritance pedigree

Answer 21

• mother with mtDNA mutation will pass mutation to all of her offspring

Question 22

sum rule

Answer 22

• probably that any one of a number of events will occur
• mutually exclusive
• sum of probabilities

Question 23

product rule

Answer 23

• probability that multiple events will occur
• independent of each other
• product of probabilities