Patterns of Inheritance

Question 1

What is Pleiotrophy?

Answer 1

A mutation that can produce multiple distinct phenotypes that may or may not appear in a particular individual

Question 2

What is a kindred?

Answer 2

A group of human beings each of which is related, genetically or by marriage to ever other member of the group

Question 3

What is the proband?

Answer 3

Family member who draws attention to a pedirgree

Question 4

What is an index case?

Answer 4

the clinically affected family member through whom attention is first drawn to a pedigree of particular interest to human genetics

Question 5

What is penetrance?

Answer 5

The probability that a gene will have any phenotypic expression at all

Question 6

What is expressivity?

Answer 6

The severity of expression of the phenotype

Question 7

What are the characteristics of Autosomal dominant inheritance?

Answer 7

• Multiple generations affected
• Males and females are affected in equal proportion
• Male to male is possible
• Each offspring of an affected parent has a 50% of being affected

Question 8

Describe Polycystic Kidney disease.

Answer 8

• Autosomal dominant
• Renal cysts, progressive renal failure, extrarenal problems
• Late onset

Question 9

What are the characteristics of Autosomal recessive inheritance?

Answer 9

• Males and females are equally likely to be affected
• Both parents must be carriers to have an affected child
• Recurrence risk is 25% for each offspring of carrier parents
• Certain diseases are more common to certain ehtnicities
• Inquire about consanguinity

Question 10

Describe Tay-Sachs disease.

Answer 10

Autosomal recessive

Severe mental and physical deterioration and death by 2 or 3

Higher incidence in Ashkenazi Jews

Question 11

Describe Phenylketonuria (PKU)

Answer 11

Autosomal recessive

Mental retardation, fair skin, eczema, epilepsy

Preventable if prompt dietary treatment

Question 12

What is Consanguinity?

Answer 12

A genetic relationship where individuals have at least one common ancestor in the preceding few generations

Question 13

What is an isonymous marriage?

Answer 13

Marriage between persons with the same surname

Not necessarily indicative of consanguinity

Question 14

What are the characteristics of X-linked recessive inheritance?

Answer 14

• Incidence much higher in males
• All daughters of affected males will be carriers
• Sons of females have a 50/50 chance

Question 15

Lyonization may make symptoms milder in X-linked recessive disorders. What are some exceptions to this?

Answer 15

• Turner Syndrome (XO)
• Extreme lyonization
• Patients carrying X:autosome translocations

Question 16

Describe Hemophilia A.

Answer 16

• X-linked recessive

- Coagulation disorder leading to hemorrhaging

Question 17

Describe Duchenne muscular dystrophy

Answer 17

• X-linked recessive

- Progressive muscle weakness, pseudohypertrophy of calf muscles

Question 18

What are the characteristics of X-linked dominant inheritance?

Answer 18

Twice as many affected females as males in large population

Affected heterozygous females should transmit to half of offspring

All daughters of affected males will be affected

Question 19

Describe Rett syndrome

Answer 19

Rare mental retardation syndrome in females, lethal in males

Ataxia, dementa, seizures

X-linked dominant

Question 20

Describe Hypophosphatemic rickets (Vit D resistant rickets).

Answer 20

X-linked dominant

Ability of kidney to reabsorb phosphate is reduced leading to hypophosphatemia

Question 21

What are the characteristics of mitochondrial inheritance?

Answer 21

Maternal origin

All offspring of an affected or carrier female are at risk of becoming affected themselves

All daughters of an affected or carrier female are at risk of transmitting the disease

Question 22

Describe Lever’s hereditary optic neuropathy (LHON)

Answer 22

Rapid, bilateral loss of central vision do to optic nerve death

Affects males and females

Mitochondrial inheritance

Question 23

Describe Kearns-Sayre Syndrome

Answer 23

External ophthalmoplegia

Pigmentary degeneration of the retina and cardiomyopathy

Mitochondrial inheritance

Question 24

What are the characteristics of Y-linked (holandric) inheritance?

Answer 24

Only males are affected

Only father to son transmission

Question 25

What are is pseudoautosomal inheritance?

Answer 25

Pertains to set of genes carried by both the X and Y chromosome, involved with a disorder known as sex reversal

Question 26

What are the clues to a translocation in a pedigree?

Answer 26

Recurrent miscarriages Unexplained infertility Mental handicap associated with unusual or dysmorphic appearance in more tha one individual related through phenotypically normal parents Child or stillbirth with multiple malformation

Question 27

What are the 5 drivers for variation from Hardy-Weinberg equilibrium?

Answer 27

Mutation Gene flow Selective mating Genetic drift Selection