Transmission Genetics I 10/23/2013 9:23:00 PM

Crosses
Involves taking two parents, mating them, observing the phenotype
of their progeny, and comparing it to that of the parents.
Gives an idea of how traits are passed.

True-Breeding Varieties (Stock) Individuals who are homozygous for a

trait and will only produce progeny with the parental phenotype.

Reciprocal Crosses
Involves crossing two individuals, each true-breeding for a
different trait then doing another round of crossing but this time,
with two the male being true-breeding for the phenotype of the
female last time and vice versa.

Phenotypes
Controlled by genes/genotype.

Diploid
Two copies of a gene. One from each parent.

Test Cross
Designed to observe the genotype of an individual.
Mate individual with unknown genotype with a homozygous
recessive individual for a trait and observe the phenotype to make a
conclusion about the genotype.

Back-Cross
Crossing a filial generation back with the parent to produce a
progeny that is more genetically identical to the parent. Often used
in horticulture.

What did Mendel Do?

Found that each phenotype was controlled by a single gene.
There are two alleles per gene.
Alleles can be dominant or recessive.
Law of Segregation
States that alleles, for the same gene will segregate themselves
into individual gametes.

Law of Independent Assortment

States that genes, as long as they are not on the same
chromosome, will assort themselves independently of one another.
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Mendel Found:
The F1 progeny of a cross between two true-breeding
lines establishes the dominance of the phenotype.
The F2 progeny established the Law of Segregation

Dihybrid Cross Type of cross that involves two genes.

When crossing two pure-breeding individuals (Round,
Yellow x Wrinkled, Green) you get a heterozygote F1 for
both traits.
If you self-fertilize F1, you get a phenotypic ratio of
9:3:3:1

Law of Independent Assortment

Different traits are controlled by different genes.
As long as those genes are located on separate
chromosomes, they will assort themselves independently
into gametes.

Pedigrees Autosomal Recessive

Tends to skip generations.
Two unaffected parents can have an affected child.
o Parents are carriers of the recessive disease in this
case.
Two homozygous parents will have all affected children.

Pedigrees Autosomal Dominance

Shows up in every generation.
Affected parent x unaffected parent can result in affected
children.

Problems with pedigrees

Human families are small.
Doesnt give you the whole picture.
If you are looking at a supposed Autosomally
Dominant pedigree, it is possible for Rr x rr to have all
unaffected children.
 Humans dont have enough kids to give you the big
picture.
How do you reconcile observation with expectation?
o CHI-SQUARED TEST

CHISQUARE TEST
(Observed Expected)^2 = x^2
Expected
Degree of Freedom (df) = # of categories 1
Compare to P value
If P > 0.05, then you fail to reject the null.
P < 0.05, you can reject the null.
Chromosomal Basis Of Heredity 10/23/2013 9:23:00 PM

Ploidy
Ploidy tells us how many copies of each chromosome we
have.
Haploid Just one copy of a chromosome.
Diploid Two copies of a chromosome (one from mom
and one form dad in humans
o Human have 23 pairs of chromosomes total in each
somatic cell.

Cell Division
Two types: Mitosis & Meiosis

Mitosis
Why?
o Growth & Repair
What type of Cell
o Somatic Cell
Every cell besides sex cells
Goal
o To create a daughter cell that is exactly identical to
the parent cell.
In humans
o Start with a diploid cell, end with two diploid cells

Cell Cycle
G1 Active gene expression and cell activity. Prepares
for DNA replication.
S phase DNA replication occurs here.
o 2n 4n
G2 Preparation for cell division
M Phase Mitosis or Meiosis

Mitosis in Detail (2n -> 4n -> 2n)

Interphase Chromosomes duplicated, microtubule
growth started
 Prophase Centrosomes begin moving to opposite
poles, chromosomes condensed.
Prometaphase Nucleus breaks down, kinetochore
microtubules attach to chromosomes and non-
kinetechore microtubules grab onto each other.
Metaphase Chromosomes line up on metaphase plate.
Anaphase Homologous Chromosomes are separated
Telophase and Cytokinesis Cells divide, and nucleus
starts to reform in each.

Regulation of Mitosis
Mitosis is regulated at many different stages by different
genes.
The cell cycle has checkpoints. Cells that reach a certain
checkpoint just meet some requirements before it can go
on to the next stage in the cell cycle.

How is Mitosis related to cancer?

Cancer is unregulated cell division.
There are genes related to cancer.
o Tumor Suppression Gene A gene whose wild-
type function is to prevent progression to the next
cell cycle if the gene does not meet some
requirements.
o Proto-Oncogene Wild type function is to
stimulate cell division.

Meiosis (2n -> 4n -> 2n -> n)

Meiosis I - Exactly the same as Mitosis.
Meiosis II No DNA replication. During Anaphase II,
sister chromatids are split.

Reciprocal Crossing D. melanogaster

Revealed that different sexes have different
chromosomes.
Show that there were X-linked Genes
X-Linked Disorders in Humans (recessive unless otherwise
stated)
Colorblindness
Hemophilia A
Male Pattern Baldness
Duchene Muscular Dystrophy
Rett Syndrome (Dominant)

X-linked disorders may skip generations

Chromosomal Basis Of Heredity II 10/23/2013 9:23:00 PM

X-Linked Dominant
Trait appears equally in males and females.

Calvin Bridges
Discovered the non-disjunction event through mating
drosophila.
Expected only red-eyed females and white eyed males in
the F1
o However, found that 1/2000 of the progeny were
exceptional, meaning that they were white-eyed
females or red eyed males.
o This is due to Non-disjunction
Bridges proposed that exceptional females were XXY.
o Y came from Dad, XX came from mother due to
failure to separate homologous X chromosomes in
females during meiosis.
Gametes end up with XX and O
o Exceptional males were XO meaning they had no Y
chromosomes.
Ultimately fund that genes and chromosomes are co-
inherited
o Therefore, genes must be on chromosomes.

Sex Determination
Different across species
In humans, Y is required for male development.
In drosophila, a single X develops as male and two X as
female.

Dosage Compensation
In female mammals, there exists a mechanism to equalize
the amount of expression of genes on the X chromosome
with that of males.
This is called X-Inactivation.
 One of the X chromosomes are silenced in females and is
turned into a transcriptionally inactive structure known as
a barr body.

Aneuploidy
An abnormal number of chromosomes in a cell.
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Loss of Function Mutations

Null/Amorphic One allele loses function but the other
still works.
o If that one allele is enough to produce a normal
phenotype, individual is haplosufficient
o If that one allele is not enough to produce a normal
phenotype, individual is haploinsufficient.
Leaky/Hypomorphic One allele does not get
expressed as much as the wild-type.
Dominant Negative Mutation Allele produces an
abnormal gene product which goes on to abnormally
interact with other gene products.

Gain of Function Mutations

Hypermorphic Mutation One allele is overly
expressed.
o Homozygotes for this mutant allele may be lethal.
Neomorphic Mutation One allele gains a completely
new/different function.

Incomplete Dominance
One allele is not completely dominant over the other.
Results in phenotype that is different from the
homozygous recessive and dominant however it more
closely resembles the dominant.

Codominance
Type of dominance in which both alleles for the same
gene are expressed equally and are expressed in the
phenotype.

Allelic Series
Many alleles for one gene but there is an order of
dominance

Lethal Mutation
 Mutation that results in inviable progeny.

Sex-Limited Traits
Traits whose dominant characteristics depends on the
sex.
Beards for example are dominant in males but not
recessive in females.

In complete Penetrance Phenomena in which some

individuals with a certain genotype show the associated
phenotype but others dont.
For example, polydactyl.
o Some individuals with the genotype have the extra
finger.
o Some dont have the extra finger.

Variable Expressivity Phenomena in which there are varying

degrees of expressivity for a particular genotype.
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Gene x environment
Some genes arent shown in the phenotype unless youre
in a certain environment.
For example, Phenoketonuria (PKU), is a disease in
which an individual cannot metabolize Phenylalanine.
Can be solved simply by not eating things with Phe in it.

Pleiotropy
When one single gene mutation affects many different
phenotypes.
For example, Sickle Cell Anemia.

Genes in pathways
Many genes interact with one another via pathways.
Gene for Insulin for example interacts with other genes
involves in glycolysis for example.
Can also be seen in eye pigment for flies.
o Eye color is coded through a biosynthetic pathway
with multiple inputs whose output is combined at the
end to create the phenotype.

How to order genes in pathways?

Beadle & Tatum worked with Neurospora mutants
Irradiated Neurospora, then placed them on minimal
media (Media that contains enough nutrients to barely
survive) to separate the prototrophs from auxotrophs.
o Auxotrophs will die.
Then transfer the auxotrophs onto different minimal
media, each containing something different.
o They will grow on the supplement that they cannot
synthesize.
Beadle and Tatum found out that colonies grew on the
minimal media supplemented with amino acids.
Then placed auxotrophs on 20 different mediums, each
containing a different amino acids.
 o The one they grow on is the amino acid that they are
missing.
In Beadle and Tatums case, it was the Methionine.
Hypothesized that one gene coded for one enzyme.

Horowitz
Using Beadle and Tatums data, Horowitz asked, are
mutants for the same phenotype mutants for the same
genotype as well?
Tested this question by removing intermediates in the
biosynthetic pathway for methionine and observed which
compound accumulated.

For example, look at Met 2 mutant strain

This auxotroph does not have the enzyme to convert
Cystathionine to Homocysteine, so naturally, it would be
stuck at the cystothionine point in the biosynthetic
pathway.

Epistasis To stand on top of

Refers to the interaction between genes.
An allele of one gene affects the phenotype of another.
Complementation Test (Cis-Trans Test)
Background:
o You have two auxotrophs for Methionine
o One auxotroph is mutant for Gene A
o The other auxotroph is mutant for Gene B.
o Theoretically, each should have a normal copy of the
opposite Gene.
Involves getting two mutants for the same phenotype and
crossing them.
Two possible outcomes.
o Progeny will be mutant That means that the
mutation is in the same Gene. COMPLEMENTATION
FAIL
o Progeny will be wild-type Genes compliment,
the mutation is in different genes. Progeny got the
normal genes!
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