DNA According to Watson & Crick (1953)

Information is in the sequence of steps
T
A
C
G
T
G
G
A
A
A
T
C
G
C

DNA
Gene
Chromosome
Protein

Chromosomes, cells, and people
Meiosis
Meiosis

Problems with cell division: Down Syndrome
Chromosome 21

Problems with cell division: Cancer
Normal Cell
Obeys strict rules
Divides only when told to
Dies rather than misbehaving
Stays close to home
Careful with chromosomes
At least 5 mutations
Cancer Cell
Disobeys rules
Divides at will
Bad behavior doesn’t kill
Wanders through body
Careless with chromosomes

Cancer cells are careless with their chromosomes
Normal cell
46 chromosomes
Cancer cell
80 chromosomes

The cell division cycle

Segregating your chromosomes wrong

Chromosome loss causes retinoblastoma

Segregating your chromosomes right
NEEDED :Chromosome segregator and cell divider
Chromosome attacher
Sister chromosomes face back-to-back
Checking mechanism (the spindle checkpoint)

Sisters bound to oppose

The spindle: locomotive tracks for chromosomes

Microtubules fish for chromosomes

Everything ready to go

A snip sets sister chromosomes free

The spindle checkpoint controls the scissors
Spindle
Checkpoint

Waiting fixes some defects…..
Time

…..but not others
X
Time

Linking chromosomes in meiosis

Reorienting errant chromosomes (B. Nicklas)

Brewer’s yeast: A geneticist’s best friend

Using jellyfish to see in the dark

Marion Shonn

The spindle checkpoint prevents errors in meiosis I
Wild Type
Checkpoint mutant
98 % 81 %
2 % 19 %

Does the checkpoint help align chromosomes?

Down Syndrome births rise sharply with age
1/33
1/40
1/50
1/67
1/100
1/200
0
25 30 35 40
Mother's Age
45 50

Chromosome linkage is different in Down Syndrome
Rarer in Down syndrome More common in Down syndrome
BUT, all linkage has occurred by mother’s birth

Rate increases with maternal age
No overall change in recombination
Less recombination near centromere
More recombination near telomere

Chromosome Alignment by Trial, Error Correction, and Delay

Meiosis I Homolog Alignment

Chromosome Reorientation in Meiosis I

Chromosome Reorientation in Meiosis I