Transcript Part 1

Today:
• Microbial Genetics
Wrap-up
• Mendelian Genetics
•Adding Chromosomes
to the Mix??
Tomorrow: UW Fieldtrip!
Back to Eukaryotes:
Bringing in Mendel…
If DNA replication
and cell division are
both so precise, and
so accurate, why
are we all so
unique??
Meiosis Creates Genetic Diversity:
1. Independent Assortment
Homologous
Chromosomes are
INDEPENDENTLY
(randomly)
parceled out during
Meiosis I
INDEPENDENT ASSORTMENT contributes to
GENETIC DIVERSITY
2. CROSS-OVER
produces
RECOMBINANT
CHROMOSOMES,
contributing to
GENETIC DIVERSITY
Cross-over occurs as
duplicated chromosomes
pair with their homologues
in SYNAPSIS. During this
process, nonsister
chromosomes cross at
CHIASMATA.
#3: Random Fertilization
8 million possible
chromosome
combinations in
each egg, and
each sperm…
= >70 trillion
possibilities!
How are we able to predict ANYTHING
about inheritance??
Looking forward to Genetics: The Paradox
Gregor Mendel, 1822-1884
Charles Darwin, 1809-1882
Setting the Stage
for Mendel
Leading theory at the
time is Blended
Inheritance
Mendel will need a
good model organism!
What
makes a
good
model??
Mendel’s
Technique:
Studies peas:
•Typically SelfFertilizing
•Multiple distinct
CHARACTERS, with
easy to identify TRAITS
•Several TRUEBREEDING varieties
available
What Mendel Observes, Part 1:
What does
this data
suggest
about
“blended
inheritance”?
What Mendel Observes, Part 2:
What does
this data
suggest
about
“blended
inheritance”?
How would you explain
Mendel’s results? (Can
you reconcile what he
observed with what we
know about
chromosomes and
meiosis??) Create a
hypothesis to explain his
new results!
Mendel’s Hypothesis- Part 1
Different genes
account for
the variation in
inherited
characters
Mendel’s Hypothesis- Part 2
For each
character, an
organism
inherits two
alleles, one
from each
parent.
Mendel’s Hypothesis- Part 3
If the alleles are different,
than one will control the
organism’s appearance
(the dominant allele) while
the other will have no
noticeable effect (the
recessive allele)
Mendel’s Hypothesis- Part 4
The two alleles are
separated during
gamete production
(At what stage??)
Testing the Law of Segregation:
The Punnett Square
The Punnett Square for Mendel’s
Experiments:
What will the F1 Generation look
like? The F2 Generation?
The Punnett Square for Mendel’s
Experiments:
vs
Understanding the predicted results
of a PUNNETT SQUARE, allows for a
TESTCROSS
What’s my
phenotype?
My
genotype?
Try a Test Cross!
Part 1: In dogs, there is an hereditary deafness caused by
a recessive gene, “d.” A kennel owner has a male dog
that she wants to use for breeding purposes if possible.
The dog can hear, so the owner knows his genotype
is either DD or Dd. If the dog’s genotype is Dd, the owner
does not wish to use him for breeding so that the deafness
gene will not be passed on. This can be tested by
breeding the dog to a deaf female (dd).
Draw the Punnett squares to illustrate these two
possible crosses. In each case, what percentage/how
many of the offspring would be expected to be hearing?
deaf? How could you tell the genotype of this male dog?
Using Simple Mendelian Genetics
Sickle Cell Disease
Sickle Cell Disease Questions:
Part 2A: Two individuals who are heterozygous
at the Sickle Cell locus have four children
together. One of the children is affected with
the disorder. Based on this information, is the
sickle cell trait dominant or recessive?
Sickle Cell Disease Questions:
2B. If the affected offspring has a child with an
unaffected individual (who does not carry the
sickle allele), what is the probability that any
given child will be unaffected? Be a carrier?
Be affected?
An Aside: Unusual Gene Frequencies!?
What do you
notice?
What does
this suggest?
Mendelian GeneticsExample 3:
Cystic Fibrosis is also an
Autosomal Recessive Trait
with Unusual Gene
Frequencies
A. If two carriers of the cystic fibrosis trait have
children, what is the probability that their first
child will be affected?
B. If they eventually have three children, what
is the probability that all three will be
affected?
Calculating
Probabilities
Huntington’s Disease
Figure 1. Samples of coronal and sagittal magnetic
resonance imaging from a patient with Huntington's
disease (top row) and a normal control (bottom row)
showing the outlines of caudate and putamen (left),
cerebral (center) and cerebellar volumes (right).
H.H. Ruocco, I. Lopes-Cendes, L.M. Li, M. Santos-Silva and F. Cendes. 1129 Striatal and extrastriatal
atrophy in Huntington’s disease and its relationship with length of the CAG repeat. Braz J Med Biol Res
2006; 39: 1129-1136
Mendel’s Next Question: What
happens in a dihybrid cross?
Dependent Assortment?
What would the
outcome look
like if it’s
dependent
assortment??
What
Mendel
Sees:
So is it
dependent
assortment??
Try a Messy Dihybrid
Cross!
5A. What fraction (or number) of the
offspring of the couple described
would be homozygous tongue-rollers
who are non-tasters (RRtt)??
Mendel’s Contributions
Law #1: Segregation
Law #2: Independent
Assortment
Complication #1: (Mendel was lucky!)
INCOMPLETE
DOMINANCE
Heterozygotes have a
unique phenotype,
between that of the
homozygous dominant
or recessive parents.
Note: This is not
blended inheritance!
Why?
Complication #1: (Mendel was lucky!)
INCOMPLETE DOMINANCE
Another Exception:
Codominance
In codominance, both alleles affect
the phenotype in separate,
distinguishable ways.
Example:
•Human blood groups M, N, and MN
Group MN produce both
antigens on the surface of blood cells
Another Exception:
Codominance
Example:
Tay-Sachs diseaseHeterozygous individuals
produce both functional,
and dysfunctional enzymes.
organismal level = recessive
biological level = codominant
A section of the brain of a Tay
Sachs child. The empty vacuoles
are lysosomes that had been filled
with glycolipid until extracted with
alcohol in preparing the tissue.
Three Important Points about
Dominant/Recessive Traits:
1. They range from complete dominance 
incomplete dominance  codominance.
(can be a subtle distinction!)
2. They reflect mechanisms through which
specific alleles are expressed in the
phenotype (i.e. this is not one allele subduing
another at the DNA level)
3. They’re not related to the abundance of an
allele within a population!
Further Complications:
Multiple Alleles
Further Complications: Multiple Alleles
Practice Question 6:
Paternity Testing
Scenario : Suppose mother is
Type A, baby is
Type B.
Consider these three putative fathers: can any
be the biological father?
#1 (Type A): Yes or No?
#2 (Type B): Yes or No?
#3 (Type O): Yes or No?
Further Complications: Pleiotropy
Most genes have multiple phenotypic
effects!
Further Complications: Pleiotropy
No production of melanocytes
during development causes:
1. White fur color and
2. Inability to transmit electrical signals
to brain from hair cells in the ear.
More Complications:
EPISTASIS
Example:
The “color gene”, C,
allows pigment to be
deposited in hair.
When lacking, a
mouse is albino,
regardless of its
genotype at the
other locus.
Epistasis and Lab
Pups
Coat color in labradors is
determined by 2 genes, a
pigment gene (B), and a
pigment delivery gene (E).
Black is dominant to Brown, so Heterozygotes
(Bb) are black. The delivery gene is also
dominant, so EE or Ee individuals both
express their pigments. Only ee individuals
are yellow.
Epistasis and Lab
Pups
Your Question (7):
If I cross a Brown Lab (bbEe)
with a Black Lab (BbEe),
can I expect any yellow
puppies?
If so, what proportion of the pups
would I expect to be yellow?
There’s
more…
Polygenic
Inheritance
This results in a
broad norm of
reaction
Other Issues: Environmental Effects on
Phenotype
Many factors,
both genetic
and
environmental,
influence the
phenotype.
Similarities between the behavior of
chromosomes and Mendel’s
“factors”:
Similarities between the behavior of
chromosomes and Mendel’s
“factors”:
•Chromosomes and genes are both present in
paired in diploid cells
•Homologous chromosomes separate and
alleles segregate during meiosis
•Fertilization restores the paired conditions for
both chromosomes and genes
Similarities between the behavior of
chromosomes and Mendel’s “factors”:
In 1902 the Chromosome
Theory of Inheritance was
proposed. In states that
Mendelian genes have specific
loci on chromosomes, and
these chromosomes undergo
segregation and independent
assortment.
Correlating
the results of
Mendel’s
dihybrid
crosses with
the behavior
of
chromosomes
during meiosis
Thomas Hunt Morgan’s
contributions: Fruit Fly
Genetics
• Single mating produces
100+ offspring
• A new generation can be
bred every two weeks
• Only four pairs of
chromosomes- 3 pairs of
autosomes, 1 pair sex
chromosomes (XX and XY)
Unlike Mendel,
Morgan does not
have access to truebreeding strains.
He breeds flies for a
year, looking for
distinct varieties.
He discovers a male
fly with white eyes,
instead of red.
In Drosophila,
red eyes = Wild type (the
most common phenotype in
a natural population)
white eyes = a Mutant
Phenotype.
Morgan’s Results:
First Experiment:
Morgan crosses a redeyed female with a
white-eyed male. ALL
the offspring have red
eyes.
How would Mendel
explain these results??
What would Mendel do
next??
Morgan’s Results:
Next Experiment:
Morgan crosses two
of the red-eyed F1
flies with each other.
What should he see
if Mendel is
correct??
Morgan’s Results:
He DOES find a
3:1 ratio, but
ALL the whiteeyed flies are
male!!
Was Mendel
wrong?? What
happened?!?