Section 5

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

VILLAIN LECTURE DISCUSSION

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

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)

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) boy!

It’s a (healthy) girl!

It’s a (healthy) girl!

It’s a boy…without another X gene to

compensate

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

• 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

X-linked mutations

X-linked mutations

50:50Majority of cells express normal (un-mutated) X

Majority of cells express mutant X

• 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

X-linked mutations

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

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?

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)

Testing hormones of pregnancy