Inheritance Patterns

Question 1

Autosomal Dominant

Answer 1

Affected offspring typically have one affected parent and one non-affected parent
Vertical transmission
Equal number males and females affected
Expected recurrence of 50%
Autosomal dominant de novo mutations increase with advanced paternal age

Question 2

Autosomal Recessive

Answer 2

Parents of an affected offspring are carriers
Horizontal transmission
Equal number of males and females affected
Expected recurrence of 25%

Question 3

X-Linked Recessive

Answer 3

Vertical transmission with “skipped generations”
Much more frequent in males than females
If carrier mom: 50% sons will be affected; 50% daughters will be carriers
If affected dad: 100% daughters will be carriers; all sons will not be carriers or affected

Question 4

X-Linked Dominant

Answer 4

Vertical transmission
Can be lethal in males
About 2:1 females to males affected
Carrier mom: 50% of sons affected; 50% of daughters affected
Affected dad: all daughters affected; no sons affected

Question 5

Y-Linked

Answer 5

Holandric
Vertical transmission
100% males only
Only passed from father to all of sons

Question 6

Mitochondrial

Answer 6

Inherited exclusively from mother
All children of an affected mother are affected if penetrance is complete
Heteroplasmy may cause variable expressivity and incomplete penetrance within families

Question 7

Imprinting

Answer 7

Phenotype depends on which parent passed on gene or is considered active

Question 8

Mutifactorial

Answer 8

Caused by a combination of genetic and environmental factors
May be considered polygenic
No characteristic pattern of inheritance
RR typically based on empiric risks
RR may be higher based on degree of relationship to affected individual, more than one individual affected, more severe phenotype, and/or if phenotype is more common in one sex but occurs in other sex (threshold)

Question 9

Reduced penetrance

Answer 9

Limitation
Individual with disease genotype does not seem to be affected
Offspring still at risk

Question 10

Age-dependent penetrance

Answer 10

Limitation

Symptoms of disease may not occur until older age after individuals have already started families

Question 11

Variable expressivity

Answer 11

Limitation
Severity of phenotype varies within family
Factors than may influence expressivity: environmental exposures, modifier genes

Question 12

Anticipation

Answer 12

More severe phenotype and/or earlier risk of onset in more recent generations
If expansion of repeats: expansion may be more likely depending on which parent passes on the condition

Question 13

De novo mutation

Answer 13

New mutation in one individual with no history of disease in family
Typically causes an autosomal dominant condition
Cannot rule out germline mosaicism (RR is not 0!)

Question 14

Skewed X-linked inheritance

Answer 14

X-linked recessive disorders

Causes manifesting heterozygotes (females)

Question 15

Phenocopy

Answer 15

Individual with similar phenotype does not have disease-causing gene and was likely caused by other factors

Question 16

Consanguinity

Answer 16

More likely to have autosomal recessive disorder

The rarer the recessive disorder, the more likely consanguinity is a factor

Question 17

Small family size

Answer 17

Limitation in assessing family history as pattern of inheritance may not be evident

Question 18

Sex-limited or sex-influenced

Answer 18

Phenotype may be more likely to occur or may vary in severity in one sex over the other