Today: Today:

• Microbial Genetics Wrap-up

• Mendelian Genetics

•Adding Chromosomes to the Mix??

Tomorrow: UW Fieldtrip!

Back to Eukaryotes:Back to Eukaryotes:Bringing in Mendel…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 Meiosis Creates Genetic Diversity:Diversity: 1. Independent 1. Independent

AssortmentAssortment

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 Fertilization8 million possible

chromosome combinations in each egg, and each sperm…

= >70 trillion possibilities!

How are we able to predict ANYTHING about inheritance??

Gregor Mendel, 1822-1884

Charles Darwin, 1809-1882

Looking forward to Genetics: The Paradox

Setting the Stage Setting the Stage for Mendelfor 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 Self- Fertilizing

•Multiple distinct CHARACTERS, with easy to identify TRAITS

•Several TRUE-BREEDING varieties available

What Mendel Observes, Part 1:

What does this data suggest about

“blended inheritance”

?

What does this data suggest about

“blended inheritance”?

What Mendel Observes, Part 2:

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

For each character, an

organism inherits two alleles, one from each parent.

Mendel’s Hypothesis- Part 2

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 3

The two alleles are separated during

gamete production

(At what stage??)

Mendel’s Hypothesis- Part 4

Testing the Law of Testing the Law of Segregation: Segregation:

The Punnett SquareThe 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 GeneticsUsing 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 An Aside: Unusual Gene Frequencies!?Frequencies!?

What do you

notice? What does

this suggest?

Mendelian Genetics- Example 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 Calculating ProbabilitieProbabilitie

ss

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 

Dependent Assortment?Dependent Assortment?

Mendel’s Next Question: What happens in a dihybrid cross?

What would the outcome

look like if it’s dependent

assortment??

What What Mendel Mendel Sees:Sees:

So is it dependent assortment

??

Try a Messy Try a Messy Dihybrid Cross!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 ContributionsMendel’s Contributions

Law #1: SegregationLaw #1: Segregation

Law #2: Independent Law #2: Independent AssortmentAssortment

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 disease-

Heterozygous individuals produce both functional,

and dysfunctional enzymes. 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. organismal level = recessive

biological level = codominant

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

       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?

Practice Question 6: Paternity Testing

Further Complications: PleiotropyFurther Complications: Pleiotropy

Most genes have multiple phenotypic effects!

Further Complications: PleiotropyFurther Complications: Pleiotropy

No production of melanocytes No production of melanocytes during development causes:during development causes:

1. White fur color 1. White fur color andand

2. Inability to transmit electrical 2. Inability to transmit electrical signals to brain from hair cells in signals to brain from hair cells in the ear.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 Epistasis and Lab PupsPups

Black is dominant to Brown, so Heterozygotes Black is dominant to Brown, so Heterozygotes (Bb) are black. The delivery gene is also (Bb) are black. The delivery gene is also dominant, so EE or Ee individuals both dominant, so EE or Ee individuals both express their pigments. Only ee individuals express their pigments. Only ee individuals are yellow.are yellow.

Coat color in labradors is Coat color in labradors is determined by 2 genes, a determined by 2 genes, a pigment gene (B), and a pigment gene (B), and a pigment delivery gene (E).pigment delivery gene (E).

Your Question (7):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?

Epistasis and Lab Epistasis and Lab PupsPups

There’s There’s more… more…

Polygenic Polygenic InheritanceInheritance

This results in a broad norm of reaction

Many factors, both genetic

and environmental, influence the phenotype.

Other Issues: Environmental Effects on Phenotype

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.

Similarities between the behavior of chromosomes and Mendel’s “factors”:

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 true-breeding 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:Morgan’s Results:

First Experiment: First Experiment:

Morgan crosses a red-Morgan crosses a red-eyed female with a eyed female with a white-eyed male. ALL white-eyed male. ALL the offspring have red the offspring have red eyes.eyes.

How would Mendel explain these results??

What would Mendel do next??

Next Experiment: Next Experiment:

Morgan crosses two Morgan crosses two of the red-eyed F1 of the red-eyed F1 flies with each flies with each other.other.

What should he see if Mendel is correct??

Morgan’s Results:Morgan’s Results:

He DOES find a He DOES find a 3:1 ratio, but 3:1 ratio, but

ALL the ALL the white-eyed white-eyed

flies are flies are male!!male!!

Was Mendel wrong?? What happened?!?

Morgan’s Results:Morgan’s Results: