Lecture 39

Question 1

In XR inheritance, A is (blank) and a is (blank)

Xa/Y = blank
XA/Xa = blank
Xa/Xa = affected female

Answer 1

A = WT
a = mutant

Xa/Y = affected male
XA/Xa = carrier female
Xa/Xa = affected female

Question 2

What are pedigree features of XR?

Answer 2

Condition skips generations

more common in males

affected father = no affected sons, but all daughters are carriers

carrier mothers = sons may be affects, daughters may be carriers

Question 3

Hemophilia A is a type of (blank) inheritance

Answer 3

XR

Question 4

What is the gene, where is this active, and what is the mutation involved in hemophilia A?

Answer 4

F8 gene

active in liver cells, produces factor VIII-C (blood clotting protein)

mutation = loss of factor VIII-C = internal/external bleeding cannot be stopped

Question 5

Why is hemophilia A XR?

Answer 5

F8 is in the unique region of the X chromosome

Males with F8-/Y have the disease

Female F8+/F8- have normal coagulation = recessive

Question 6

How did life expectancy improve with recombinant Factor VIII-C treatment?

Answer 6

1.4 years (1900) to 65 years (2000)

Question 7

In XD inheritance, A is blank and a is blank

XA/Y is blank
XA/XA and XA/Xa is blank

Answer 7

A is mutant
a is WT

XA/Y is affected male

XA/XA and XA/Xa is affected female

Question 8

What are the pedigree features of XD?

Answer 8

Condition appears in every generation

seen in both sexes

affected mother = sons and daughters may be affected

affected father = all daughters affected, no sons affected

Question 9

What type of inheritance is fragile X syndrome?

Answer 9

XD

Question 10

What is the gene involved in fragile X syndrome? What is the mutation involved?

Answer 10

FMR1 at Xq27

encodes FMRP, needed in brain neurons

mutation: (CGG)n repeat in 5’UTR

too many repeats = gene is silenced = no FMRP

very long repeat arrays form fragile constrictions on metaphase X chromosomes

Question 11

Why is fragile X XD?

Answer 11

male FMR1-/Y = 0% of neurons make FMRP = IQ is less than 50

female FMR1+/FMR1- = 50% of neurons make FMRP = still abnormal = dominant = IQ 50-70 depending on which neurons lack FMRP

Question 12

Do nonsense mutations create fragile sites is fragile X?

Answer 12

NO

Question 13

When is the child affected by mitochondrial (M) inheritance?

Answer 13

if most/all mitochondria in the oocyte have the mutant allele

Question 14

What are the pedigree features of M inheritance?

Answer 14

affected mother = ALL children affected

affected father = no children affected

Question 15

What type of inheritance is leber hereditary optical neuropathy (LHON)?

Answer 15

M

Question 16

What is leber hereditary optical neuropathy (LHON)?

Answer 16

Mutation in mitochondrial genome, often in Complex I genes

blindness in early adulthood due to retinal cells failing (high ATP demand)

Question 17

Chloroplast mutations in plants are similar to what inheritance?

Answer 17

mitochondrial