X-Linked Inheritance and Disease

Question 1

Aneuploidy

Answer 1

More or less than 2 of each chromosome present

Question 2

Only autosomal aneuploidy that doesn’t cause death

Answer 2

Down syndrome (trisomy 21)

Question 3

Why X aneuploidies don’t cause death

Answer 3

Extra X chromosomes are randomly inactivated in order to prevent over dosage of genes

Question 4

Examples of X aneuploidies

Answer 4

Turner syndrome: X0
Trisomy and Tetrasomy X
Klinefelter’s Syndrome: XXY

Question 5

Mosaicism

Answer 5

Different cells express different X chromosomes (some express mom’s, some express dad’s)
Only present in females and males with more than 1 X chromosome

Question 6

Barr body

Answer 6

One X chromosome is compacted and inactivated in cells of females and males with more X chromosomes than normal

Question 7

Steps in inactivation of X chromosome

Answer 7

Count number of X chromosomes
Choose at random one X chromosome to inactivate 
Assemble inactivation factors
Spread along X chromosome
Establish inactive state

Question 8

How inactivation of X chromosome is carried out

Answer 8

Underacetylated histones (enabling histones to bind DNA tightly)
Methylated CpG islands (methylation shuts down transcription of DNA)
Delayed DNA replication

Question 9

X inactivation center (XIC)

Answer 9

Area of X chromosome where inactivation is initiated and spreads from
Contains X inactive specific transcript gene (XIST)

Question 10

How XIST gene inactivates X chromosome

Answer 10

XIST codes only for RNA (not translated to make protein)
Instead of leaving nucleus, XIST RNA coats the X chromosome expressing it
XIST RNA recruits repressive complexes to maintain inactive strand and repels activating factors to prevent it from being transcribed

Question 11

Are all genes on the inactive X chromosome also inactivated?

Answer 11

No- about 15% of the genes remain activated

Question 12

P and Q arms of chromosome

Answer 12

P arm: short arm

Q arm: long arm

Question 13

Ectodermal Dysplasia

Answer 13

X-linked disease
Hypotrichosis (sparse, light-colored, brittle, slow-growing hair)
Absent eyebrows
Prominent forehead, broad nose, thick lips
Hypohydrosis (fewer sweat glands, leading to difficulty cooling body)
Hypodontia (few, small, pointed teeth)

Question 14

Cause of ectodermal dysplasia

Answer 14

Mutation in ectodermal dysplasia A (EDA) gene on X chromosome
Less ectodysplasin (protein) produced

Question 15

Red-green colorblindness

Answer 15

X-linked disease

Inability to distinguish red and green, or seeing red and green differently from most people

Question 16

Cause of red-green colorblindness

Answer 16

Mutations in OPN1LW, OPN1MW, and LOC728458

Causes defects in cone pigments (opsin proteins)

Question 17

Duchenne muscular dystrophy symptoms

Answer 17

X-linked recessive
Initial symptoms develop by age 5
Bent back (lordosis), waddling gait, pseudohypertrophy of calf muscles
Progressive involvement of muscles, scoliosis
Respiratory insufficiency, pneumonia, immobilization, and death by third decade

Question 18

Cause of Duchenne muscular dystrophy

Answer 18

Mutation in dystrophin gene
Dystrophin ties actin into muscle cell membrane
Muscle fiber destruction due to loss of normal protein

Question 19

Characteristics of X linked disease shown in pedigree

Answer 19

Females are carriers

Usually males are affected (only have 1 X chromosome)

Question 20

Can X linked disease carriers show disease phenotype?

Answer 20

Yes, but often not as severe