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Day 1
General information
Lecture powerpoints under resources
Pop quizzes are possible
Quizzes during discussion sessions are not for a grade but are a valuable resource
Traits and behaviors that are transmitted through generations, and understanding the biological
transmission of these traits and behaviors
We see a lot of diversity in nature
Controlled by genetics
Gregor Mendel: late 1800s for 10 years; published in 1860s
Looked into pea plants; 9 traits
CONTRIBUTIONS
Quantitative approach to research
Concepts of units of heredity
Concept of dominant and recessive traits
Had no idea about the mechanism of the transmission of traits
DNA: made of deoxyribose sugar, nucleotide, phosphate
AT and CG are complementary base pairs
“Central Dogma”: DNA, transcription, mRNA, translation with ribosome, proteins (gene product)
Genes do not necessarily code for proteins: can make tRNA, etc.
Genes may change in a cell through mutation or genetic recombination
Genes are NOT turned on all the time
Hormonal, developmental, environmental regulation, etc.
Ex. Change from gamma-globin (produced in fetal liver) to beta-globin gene expression
(produced in bone marrow) in fetus right before birth
o Change occurs because gamma-globin will become toxic, and if there is too much oxygen
in the blood, it won’t release to the cells
Sickle-cell: hemoglobin aggregates in the red-blood cells, which results in crescent-shaped red
blood cells (controlled by a single gene)
Model organisms in genetics: why use them?
Monkeys, flies, rats, bacteria
Each species is used for different purposes
Much faster reproduction
May be similar to humans, but not always
Green fluorescent protein (GFP) fused to any gene a scientist wants, and that shows when the gene is
expressed
In 1900, chromosome movements during cell division discovered
Shown that chromosomes drive genetics
DNA is packaged by wrapping around histones to form nucleosomes, which fold to make chromatin,
which condense to become chromosomes
Solves space problem, but presents difficulty in having to express the DNA (the tightly packed
DNA is hard to read)
DNA + protein in a chromosome = chromatin
Tightly packed chromatin = heterochromatin
Loosely packed chromatin = euchromatin (looks like beads on a string)
Day 2: Mitosis and Meiosis
Mitosis: somatic cells that divide in sexually reproducing organisms
Sexual reproduction produces much more genetic variation than asexual reproduction
Germ cells undergo meiosis (important for sexual reproduction)
Meiotic recombination
Centromeres are the part of DNA that connect sister chromatids (don’t have genes, but ARE made of
DNA)
Attached together by the protein cohesin
Telomere is DNA that has genes that don’t code for anything and are at the top of the chromatids; stable
ends of the chromosome
When sister chromatids are alone, they are called chromosomes, not chromatids
Chromosome 1 from mom and chromosome 1 from dad are homologous
Are alike in size and structure and carry information for the same traits
May have different alleles at different, and so are not identical
Spindle microtubules form at the kinetochore
Chromatin: DNA and protein in a chromosome
The Cell Cycle and Mitosis
Interphase: an extended period between cell divisions, DNA synthesis, and chromosome replication
phase; normal function, growth
Phase check points: key transition points that determine whether or not the cell will continue on to the
next stage of mitosis
G1 (initial growth; checkpoint at end), S (DNA synthesis), G2 (after this phase, there is a checkpoint)
phases
At the G0 stage, there is no replication or preparation for it
Occurs in most cells, means that cells are not dividing
M phase (mitotic phase)
Prophase (chromosomes condense with 2 chromatids each, spindle forms)
Prometaphase (nuclear membrane disintegrates, spindle microtubules attach to chromosomes)
Metaphase (chromosomes line up in the middle of the cell at the metaphase plate)
Anaphase (sister chromatids separate and move towards opposite poles)
Telophase (chromosomes arrive at spindle poles, nuclear membrane reforms, chromosome start to
unravel)
Cytokinesis is NOT part of mitosis: must produce new cell membrane
Cyclin-dependent kinase (CDKs): family of protein kinases that play a well-established role in the
regulation of the eukaryotic cell division cycle and have also been implicated in the control of gene
transcription and other processes
P54 RNA helicase: transcription factor, protein that binds to a specific DNA sequence to control the
transcription of DNA to mRNA
If the cell aborts the replication process after the S phase, it will have double the amount of DNA, making
it polyploidy
Can be controlled with drugs
In nature, many species are polyploidy, especially plants
All species were polyploids at one time, but some evolved later to be diploid
Mitosis produces 2 cells that are genetically identical to each other and their parent cell
Newly formed cells have a full complement of chromosomes, about half (but not necessarily identical)
cytoplasm and organelle content of parent cell
In our body, the majority of cells don’t divide, and thus do not undergo mitosis
Meiosis: the basis of sexual reproduction and genetic variation; the production of haploid gametes
Fertilization: the fusion of haploid gametes
Before meiosis is interphase: DNA is synthesizes and chromosomes are replicated
Two parts: in meiosis 1, homologous chromosomes are separated
AKA reduction division because the chromosome number is reduced in half
In meiosis 2, sister chromatids are separated
AKA equational division; chromosome number is unchanged
Methods for increasing genetic variation
Crossing over happens in prophase 1, and the intersection of the sister chromatids is called the
chiasmata
o Occurs at random places along the chromosomes, making new combinations of maternal
and paternal DNA
Random distribution of chromosomes in meiosis: when homologous chromosomes line up at the
metaphase plate in metaphase 1, and when sister chromosomes line up in metaphase 2
Meiosis 1 is very similar to mitosis except that it involves separating the homologous chromosomes
Meiosis 2 is mitosis with sister chromatids (very similar method and processes)
Cohesion: a protein that holds chromatids together; is the key to chromosome behavior
Broken down in anaphase by separase, which allows sister chromatids to separate
Holds homologs together at chiasmata along chromosome arms in meiosis
Shugoshin: only in meiosis NOT mitosis
Shugoshin protects the cohesion at the centromere during anaphase 1, which keeps the sister
chromatids together while the homologous chromosomes are being separated
Broken down during anaphase 2, which allows the cohesion to degrade, which allows the sister
chromatids to separate
Independent assortment: different way that chromosomes line up at the metaphase plate
Colchicine: hormone that inhibits microtubule polymerization during spindle formation (prophase),
preventing chromosome movement
When removed in late prophase, the cell re-enters interphase
Results in a tetraploid cell
Consequences of meiosis
Four haploid cells (1/2 original chromosomes), each genetically different from both one another
and from the parent cell
Kinetochore: the protein structure on chromatids where the spindle fibers attach during cell division to
pull the sister chromatids apart
Form in eukaryotes, assemble on the centromere and link the chromosome to microtubule
polymers from the mitotic spindle during mitosis AND meiosis
Sister chromatids start out with identical genetic material in both mitosis and meiosis
How would each of the following events affect the outcome of mitosis or meiosis?
1. Mitotic cohesin fails to form early in mitosis
a. Because cohesin is the protein that attaches sister chromatids together at the centromere
until anaphase, failure to form in mitosis would lead to the ability of the chromosomes to
separate prior to anaphase, which could result in the improper segregation of the
chromosomes.
2. Shugoshin is absent during meiosis
a. Shugoshin is the protein that protects cohesin from being degraded in the anaphase stage
of meiosis 1 and allows the sister chromatids of each chromosome to stay together until
anaphase 2. If it is absent, the sister chromatids will separate at anaphase 1 along with the
homologous chromosomes, which will lead to gametes with an incorrect number of
chromosomes.
3. Shugoshin does not break down after anaphase 1 of meiosis
a. If shugoshin does not break down after anaphase 1 of meiosis, cohesin will not be
degraded in anaphase 2. This will make the sister chromatids unable to separate and
result in improper segregation of chromosomes in the produced gametes.
4. Separase is defective
a. Separase is the enzyme that breaks down cohesin, which allows sister chromatids and
homologous chromosomes to separate in both mitosis and meiosis. If it does not work,
the chromosomes and chromatids will not separate, and the result will be gametes with an
improper number of chromosomes.
SAMPLE QUESTIONS FOR TESTS
Design a genetic screen to identify mutants affected only in meiosis but not in mitosis.
Genetic screen: test for a phenotype
Find a way to identify the presence of shugoshin
What model system would you use to perform this screen?
Would need species that reproduces with meiosis, so not bacteria
What difficulty might you face in identifying these mutants?
How would you get around these problems?
Day 3: Mendelian Genetics
Sources of genetic variation
Random fertilization
Nature of 23 chromosomes: produces 223 different combinations
We predict offspring genotypes and phenotypes with Punnett squares!
Reduction division
Gamete has ½ the alleles of the diploid genotype
Mendel: father of genetics: important postulates
1. Genetic factors occur in pairs
2. When 2 different factors are present in an individual, one unit is dominant to the other, which is
RECESSIVE (principle of dominance)
3. During gamete formation, the 2 units present in an individual separate randomly, so each gamete
receives only 1 (segregation)
a. Anaphase 2 separates sister chromatids so that each gamete ends up with only 1 copy of
each chromosome
4. Independent assortment. Genetic factors for different traits sort independently into the gametes.
a. Happens mostly in meiosis 1 during metaphase
b. Metaphase 2 produces some variation because of the results of crossing over
Meiosis 1 is when the homologous chromosomes are separated: the main place for segregation
Even though we can say with confidence that someone is homozygous, the results could be due to chance
and therefore we cannot be 100% SURE (think of example of father with 8 children who all have his
dominant trait and the mother has the recessive. While it is most probable that he is homozygous
dominant for this trait, you cannot be 100% SURE).
Probability
Recombinant frequency:
Unit: centimorgan (cM)
1 cM = 1% recombination; is a distance that they are apart
Exception: if the genes are close to the centromere. If this is the case, the recombination
frequency is extremely low regardless of where the genes are located
Summary
Gene interactions between two/more genes result in novel phenotypes
Recessive epistasis shows homozygous recessive at one locus affect the pathway
Duplicate recessive epistasis (homozygous recessive at either gene locus), because both gene
products are needed for the pathway
Dominant epistasis where one genotype produces the same dominant phenotype, regardless of
genotype at the other locus
Complementation test shows whether the two genes mutated are at the same locus or different
locus
Linked genes indicate 2 or more genes segregate with one another - basis for making linkage
group
Day 6
In some species, gender is determined by environmental or social cues rather than genotype (species like
turtles and wrasses)
In this case, they don’t have obvious sex chromosomes
Chromosomal sex determination: gender is determined by the complement of chromosomes and can be
predicted usually at the time of fertilization
A subset of genes are located on sex chromosomes that differ in number between genders
Mammals and flies use X-Y system
X-0 system in grasshoppers and nematodes (XX are female, X are make)
Z-W system in birds, snakes, butterflies (ZW are female, ZZ are male)
Haplo-diploid system in bees, wasps, ants (diploid are female, haploid are male)
Plants are grouped into monoecious and dieocious
Monoecious: one organism has both male and female reproductive parts
Dieocious: one organism has only male OR female reproductive parts
Haplodiploidy: sex determination system in which males (being haploid) produce their gametes by
mitosis rather than meiosis
When you make a Punnett square with the sex chromosomes, you must add the allele to the X or Y
chromosome
Ex. XC or Xa for an X chromosome that has the colorblindness trait
X+ or XA for a regular X chromosome
We only have the cone cells for 3 colors, red, blue, and green in our eyes
Most colorblind people have a mutation in the red and green chromosomes
Alleles for 2 blood-clotting factor (usually blood factor 8) proteins are on the X chromosome, so
hemophilia is a sex-linked condition
If a female is a carrier but her husband is unaffected, ½ of their daughters will be carriers and ¼ of their
children overall will be affected by a recessive sex-linked trait.
Pedigrees sometimes reveal whether a trait is dominant or recessive or autosomal or sex-linked
Transgene: foreign DNA that is successfully integrated into the genome of a host organism
Secondary sexual differentiation: the development of sexually dimorphic characteristics, typically as a
result of hormones
Sexual dimorphism: differences between the secondary sexual characteristics in a species
Size
Coloration
Organs of sexual display (the antlers of moose and deer)
Androgen insensitivity syndrome (AIS): genetic condition in which a person with an XY genotype is
unable to synthesize or respond to testosterone
X chromosome inactivation: occurs randomly in female mammals at a time when the embryo is
composed of 10-20 cells
Females develop as a genetic mosaic in which some tissues express the maternal X chromosome
while some express the paternal X chromosome
Occurs when RNAi (inhibitory) interacts with specific X loci, forming a Barr body with the
inactive chromosome
Is evolutionary in its basis because it ensures the X chromosome is the only one activated and
passed to the next generation
Summary
The mechanism by which sex is established is sex determination
Sex determination can be chromosomal, genetic, or environmentally regulated
Sex-linked characteristics are determined by genes on the sex chromosomes
The male-determining gene SRY is on the Y chromosome
Dosage compensation is achieved by random X-chromosome inactivation
Day 7
Parental genotypes will always have the most progeny
The reduction of chromosomes from diploid to haploid occurs in meiosis 1
Non-recombinant progeny will outnumber recombinant progeny, so whether alleles are in coupling or
repulsion configurations determines the number of offspring that have different combinations of trait
Coupling configuration: when one parent has two dominant alleles on the same chromosome, and
the other chromosome has recessive alleles at both loci in question
o When crossed in a test cross, the progeny are 4 times more likely to have both dominant
or both recessive phenotypes than one dominant and one recessive
Repulsion configuration: when the dominant alleles are located on different chromosomes in an
organism
o When crossed in a test cross, the progeny are four times more likely to have one
dominant and one recessive trait than both recessive or both dominant
χ2 test helps determine whether or not the genes are linked (observed – expected)2/expected
Df = (number of rows – 1) x (number of columns – 1)
Recombination frequencies can be used to help determine the proportion of predicted progeny
Frequency of each of the recombined gametes can be determined by dividing the recombination
frequency by 2
Even if crossing over does occur, if DOUBLE crossover occurs between the two loci being studied, the
resulting chromosomes will still be non-recombinant
The results of a three-point test cross can be used to map linked genes
Steps to determine order of 3 gene loci, using recombinant frequencies
1. Identify the non-recombinant progeny
2. Identify the double-crossover progeny
3. Compare phenotype of double-crossover progeny with phenotype of parents (they should differ in
one trait, which is the trait encoded by the middle gene)
Type of Maps
Genetic map
o Visible markers
o Molecular markers
o RFLP (restriction fragment length polymorphism)
o SSLP (simple sequence length polymorphism)
o CAPS (cleaved amplified polymorphic sequence)
Loss-of-function allele is when the heterozygote makes enough protein to still work (recessive to wildtype)
Haploinsufficiency: when having only one wild-type allele is NOT sufficient to produce the wildtype phenotype (the wild-type allele is recessive because the threshold for wild phenotype is high
for the amount of protein)
o Ex. Muscular dystrophy, loss of function of the protein dystrophin (dystrophin connects
the actin cytoskeleton to the extracellular matrix of muscle fiber
Null allele – when the allele produces no functional gene product
Gain-of-function allele: produces increased activity of the gene product
Mutations in promoters can increase the level of gene expression or express the genes in tissues
where it is not normally expressed
These mutations are rare because there are so many ways to produce harmful mutations
Dominant negative: alleles that are dominant to the wild-type allele because they encode a mutant gene
product that interferes with the functioning of the wild-type gene product
The heterozygote’s wild-type proteins are insufficient to produce the wild-type phenotype
Pleiotropy – one gene locus affects many different aspects of the phenotypes of different tissues
Ex. Sickle-cell disease and Marfan syndrome in humans
Huntington’s Disease (CAG repeats) and Fragile-X (CGG repeats) are triple-repeat disorders
(ELABORATE)
o Repeats may increase due to the formation of hairpins
Genetic anticipation – genetic disease that increases in severity in successive generations, because of
increase in number of repeats of segments on a chromosome
Sex-influenced traits – sex influences the expression of the genotype (of the heterozygote)
Ex. Male pattern baldness; the expression of the allele depends on the level of testosterone in the
hair follicles
Sex-limited traits – autosomal genotypes, but expressed ONLY in one sex
Ex. Cock-feathered tail appears in only make chickens. Female chickens never display cockfeathering, regardless of genotype
Maternal effect – pattern of inheritance in which gene products are transmitted from the mother to the
offspring via the egg
For a maternal effect gene, it is the genotype of the mother which determines the phenotype of
her offspring