1) X-linked mutations can affect males more severely than females because males only have one X chromosome, while females have two to compensate. 2) Some diseases like multiple sclerosis are more common in females potentially due to the influence of sex hormones. Experiments using mouse models of MS have provided evidence for this. 3) Studies injecting mice with myelin proteins can induce experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. This model also shows females being more severely affected, matching the sex difference seen in humans with MS.

1. Section 5

2. Announcements
• Next week
– Meet in Powell library (entrance)
– Have a specific idea for paper 2
– Download updated Sociology Study Guide and
complete Questions for Tuesday and Thursday
readings

3. VILLAIN LECTURE DISCUSSION

6. Review of Dr. Arold’s Lecture 8:
Sex differences in disease

7. Why are there sex differences in the
prevalence of some diseases?
• (Why do men get some diseases more often
than women? & vice versa)
– X-linked mutations
– Autoimmune diseases (& their potential
relationship with sex hormones)

8. X-linked mutations
• What is an X-linked mutation?
• Why does this kind of mutation affect males
more severely than females?
Dad Mom
It’s a (healthy) It’s a (healthy) It’s a (healthy) It’s a boy…without
girl! boy! girl! another X gene to
compensate 

9. X-linked mutations
• Why are some females strongly
affected by X-linked mutations, and
other females are hardly affected at
all?
– X-inactivation
– “Turn off” one X chromosome in each
cell
– Random process! Like a coin toss.
– Toss coin 100 times, will get close to 50
heads & 50 tails

10. X-linked mutations
• X-inactivation is like a coin toss experiment
– Toss coin 100 times
• Going to get heads ~50 times, and tails ~50 times
• Every once in awhile, going to get something like 75 heads &
25 tails!
• Females’ cells are the same way
– Most of the time, about 50% of cells will turn off X
from Mom, & other 50% of cells will turn off X from
Dad
– Sometimes, number of cells turning off Mom’s X will
be skewed (for example)
– This makes a mutation on the X more or less prevalent

11. X-linked mutations
Majority of cells express Majority of cells express
50:50
normal (un-mutated) X mutant X

12. X-linked mutations
• Most X-linked diseases have a male bias (more
males have them, males affected more
severely)
• Some X-linked diseases have female bias
– Why?
– We have no idea!
– Example: neural tube closure defects
• Exencephaly

13. Autoimmune diseases
• Generally, affect more females than males
• Immune response basics:
– 1) Specificity to antigens (what is an antigen?)
– 2) HUGE capacity for diversity
– 3) Can distinguish “self” (your own cells) from
“non-self” (cells from other organisms that should
not be in your body)
– 4) Immunological memory

14. Example autoimmune disease: MS
• Females more likely to get MS
• MS onset is earlier in life for females
• Evidence for environmental factors (such as?)
• What causes sex difference in MS?
– Evidence for influence of sex hormones (such as?
What kind of evidence is this?)
– How do you test this?

15. MS & EAE
• What is EAE?
– Experimental model for MS in mice
– Induce mice to produce antibodies against their own
myelin (specifically against myelin basic protein, MBP)
• Conveniently enough, EAE affects female mice more
severely than male mice! (just like MS in humans)
• Induce EAE by:
– Directly injecting mice with MBP
– Transfer lymph node cells from injected mouse to the
mouse that you want to have EAE
• Then, measure severity of symptoms in mouse (clinical
score)

16. Testing hormones of pregnancy