Transcript Mendelian Genetics I: Ratios

• By 1924, approximately 3,000 people had been involuntarily
sterilized in America; the vast majority (2,500) in California.
“It is better for all the world, if instead of waiting to execute degenerate
offspring for crime or to let them starve for their imbecility, society can
prevent those who are manifestly unfit from continuing their kind…Three
generations of imbeciles are enough.”
Justice Oliver Wendell Holmes, Jr.
U.S. Supreme Court; Buck vs. Bell, 1927
• Buck v. Bell supplied a precedent for the eventual sterilization of
approximately 8,300 Virginians
• sterilization of people in institutions for the mentally ill and mentally
retarded continued through the mid-1970's. At one time or another, 33
states had statutes under which more than 60,000 Americans endured
involuntary sterilization.
Announcements
1. How is powerpoint slide printing going?
2. Bring FlyLab to Lab next week; meet in Brooks 101 (computer lab) for
the first part of lab
3. Homework this week: Ch.2, problems 2, 10, 13, 14, 19
(NOT turned in)
4. Answers to Ch.2 problems will be posted on Tuesday, Sept. 3 outside
my office
5. http://www.eugenicsarchive.org/html/eugenics/essay8text.html
6. Quiz today!
Review of last lecture
1. Basic concepts that underlie the study of genetics: DNA, genes,
chromosomes
2. Somatic cells have a diploid # of chromosomes (2n);
each chromosome type (except X and Y) exists as a homologous pair
3. Different forms of the same gene exist as alleles
ex. wt vs. mutant CFTR gene
4. How do scientists investigate genetics?
5. Genetics and society - eugenics, agriculture, medicine
6. Mitosis is one part of the cell cycle; important for many reasons
7. Four phases of mitosis: prophase, metaphase, anaphase, telophase
Outline of Lecture 3
I. Cell division is genetically regulated
II. Meiosis
III. Gregor Mendel - discovered basis for transmission of
hereditary traits
IV. Monohybrid cross
V. Mendel’s postulates
I. Cell division is genetically regulated
•Why are we interested in knowing how cell division is regulated?
* if regulation is disrupted, uncontrolled cell division may
result…..cancer
•Most recent Nobel Prize was awarded to 3 scientists who studied
genes that regulate the cell cycle, including Lee
Hartwell (director of the Fred Hutchinson Cancer Research
Center) who studied cell division regulation in yeast
http://www.fhcrc.org/visitor/nobel/hartwell/accomplishments.html
•There are 3 main checkpoints in the cell cycle
Three main checkpoints in the cell cycle
1.
3.
QuickTime™ and a
GIF decompressor
are needed to see this picture.
2.
1. Is cell the correct size?
Is DNA damaged?
2. Is DNA fully replicated?
Is DNA damage repaired?
3. Have spindle fibers formed?
Have they attached to
chromosomes correctly?
Why are cell cycle checkpoints important?
What might result if DNA repair has not finished?
Uncontrolled cell division could occur - cancerous cell
Example: p53 protein normally targets cells with severe
DNA damage to undergo programmed cell death.
(this removes them from the population)
If the p53 gene is mutated, damaged cells will not
be removed and may continue dividing in an
uncontrolled manner.
Many different types of cancers involve mutations of p53.
II. Meiosis
a special cell division
to make gametes (sperm and egg)
Why would a “regular” mitosis be a problem in making gametes?
If
2n
+
egg
2n
then
sperm,
4n
embryo
•Meiotic cell division generates cells (sperm and eggs) with onehalf the genetic material (2n to 1n) - a reduction in
chromosome number
•Source of genetic variation - see mechanics
Key points of meiosis
•Homologous chromosomes pair (synapse) to form
a bivalent; the four chromosomes form a tetrad.
•Recombination during meiosis is the basis for
genetic variation within species.
•Two divisions: reductional division and equational
division, each with four phases
Mitosis vs. Meiosis
• S phase: 2N  replication  duplicated 2N
• Mitosis: duplicated 2N  separation of sister chromatids 
each daughter cell is 2N
• Meiosis: duplicated 2N 
meiosis I (reduction division): separation of homologous
chromosomes  synapsis of homologous chromosomes
 recombination = duplicated N
• meiosis II (equational division): duplicated N  separation
of sister chromatids  N
• Is Meiosis I or II more like mitosis?
Meiotic Prophase I
(5 stages of prophase I)
• 1. Leptonema “slender-thread”
– Condensation: chromatin
starts to condense
• 2. Zygonema “paired-thread”
– Pairing: homologues pair
(synapsis) in synaptonemal
complex (not in mitosis)
– s.c. allows for crossing over;
if it doesn’t form, no
synapsis, no crossing over
Meiotic Prophase I (continued)
3. Pachynema “thick-thread”
Ea. tetrad has 2 pr. sister chromatids
Recombination: further condensation;
crossing over occurs
4. Diplonema “doubled-thread”
tetrads visible, chiasmata visible (where
sister chromatids contact)
5. Diakinesis “movement apart”
– Breakaway: sister chromatids pull
apart, chiasmata move to ends of
each tetrad
– NEBD, nucleolus disappears, spindle
fibers attach to centromeres
Completion of Meiosis I
• Metaphase I
– tetrads align randomly:
independent assortment
• Anaphase I
– one-half of each tetrad, a
dyad (homologue), moves to
each pole
– sister chromatids together
– separation of tetrads is
disjunction; when they do
not separate it is
nondisjunction - more ch. 10
• Telophase I
Met I
Ana I
Tel I
Meiosis II
• Mechanistically similar
to mitosis.
• Sister chromatids
separate, producing
monads.
• Four haploid gametes
can potentially form.
• If crossing over
occurred, ea. monad
has combined genetic
information
Gametogenesis:
Spermatogenesis
• Occurs after puberty,
continuously in human
males.
• Equally-sized haploid
products: sperm
• Crossing over can
occur to create genetic
recombination.
Gametogenesis: Oogenesis
• Begins during first months
of embryogenesis in
human females.
• Meiosis arrests at diplotene
of prophase I and resumes
after puberty at ovulation.
• Unequally-sized haploid
products: huge egg and
tiny polar bodies.
• Meiosis arrests again at
metaphase II and resumes
after fertilization.
Multiple Choice - self test
Which of the following is true about cell division:
a) Meiosis I is more like mitosis because it is a
reductional division (2n to 1n)
b) Meiosis I is more like mitosis because sister
chromatids separate
c) Meiosis II is more like mitosis because it is an
equational division (1n to 1n)
d) Meiosis is similar to mitosis because it generates
genetic variation
III. Gregor Mendel
• Monastery of St. Thomas,
Brno, Czech Republic.
• Taught physics and natural
science.
• Performed experiments 18561868, published in 1866.
• Why peas?
– Easy to grow
– Self-fertilize or can
hybridize artificially
– Matures in single season
– Choice of contrasting traits
How Mendel
performed his
crosses with pea
plants
Mendel’s 7 traits
1.
2.
3.
4.
5.
6.
7.
Modern genetic terminology
•Phenotype - physical expression of a trait
•Gene - Mendel’s “unit factors” of inheritance
•Allele - different forms of a gene, e.g. D or d
•Genotype - allelic composition of a trait
–e.g. DD, Dd, or dd
More modern genetic terminology
•Homozygous - genotype of identical alleles, e.g. DD or dd
•Homozygote - homozygous individual
•Heterozygous - genotype of different alleles, e.g. Dd
•Heterozygote - heterozygous individual
•Dominant and recessive - Alternative phenotypes when two
alleles are expressed.
–D is dominant and d is recessive if Dd and DD have the
same phenotype
IV. Monohybrid cross
(tall and dwarf pea plants)
Monohybrid Cross:
Punnett Square Method
(1) Define symbols:
D = tall allele
d = dwarf allele
(2) State the cross
(3) Diagram the gametes
(4) Complete the squares
(5) Summarize the results:
Genotype
Phenotype
Reciprocal crosses
•Results were the same regardless of which parent was
used, e.g.
–tall pollen pollinating dwarf eggs
–dwarf pollen pollinating tall eggs
•Therefore the results were not sex-dependent
•Mendel proposed “unit factors” to explain his results
V. Mendel’s postulates
Postulate 1. Unit factors in pairs
•Genetic characters are controlled by unit factors in pairs.
•In other words, genes are present in two associated copies in
diploid organisms.
•For example, DD plants have two alleles for tallness, dd plants
have two alleles for dwarfism.
Postulate 2. Dominance/recessiveness
•In the case of unlike unit factors, one can be dominant and
the other can be recessive.
•In other words, when two different alleles of a gene are
present, one may show its effect while the other may be
masked.
•For example, Dd plants have a tall allele D and a dwarf allele
d, but are phenotypically tall.
Postulate 3. Segregation
•During the formation of gametes, unit factors
segregate randomly.
•In other words, when sperm and eggs are formed,
one of each allelic pair is randomly distributed to to
each gamete.
•For example, a Dd plant makes pollen or eggs, each
randomly receives either the D allele or the d allele.
Practice: Axial/Terminal Pods
•In garden peas, an allele T for axial flowers is
dominant to an allele t for terminal flowers.
–In the F2 generation of a monohybrid cross,
what is the expected ratio of axial : terminal?
–Among the F2 progeny, what proportion are
heterozygous?
–Among the F2 progeny with axial flowers, what
proportion are heterozygous?
Round/Wrinkled Seeds
• Round (W) dominant to
wrinkled (w)
• What’s the molecular
basis? Starch and
sugar content
• Wrinkled seeds have
higher glucose, water
content before drying,
larger loss of seed
volume during drying
Loss-of-function in
wrinkled allele