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Q: Why is
there sex?• it’d be much faster not to have to find a mate
- just replicate on your own
sexual
reproduction
asexual
reproduction
A: Sexual reproduction increases genetic diversity
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X and Y are sex determining
chromosomes in humans and
fliesHomologous
chromosomes
X and Y have
different loci
behave as homologouschromosomes during
meiosis in males
Males are
hemizygous
for the X chromosome
XX: female
XY: male
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Another type of sexual lifestyle: C.
elegans
Hermaphrodites: self
-
fertilizing animals with sperm
and eggs
Males: animals with sperm
only that mate with
hermaphrodites
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Another type of sexual lifestyle: C.
elegans
XX hermaphrodite
XO (this means 1X) male
Convenient for genetics to self and cross
-
fertilize
XO can occur by non
-
disjunction
Figure 5-3
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Many ways to determine sex
homogametic: XX heterogametic: XY
homogametic: XX heterogametic: XO
heterogametic: ZW homogametic: ZZ
XX ; AA: diploid X ; A: haploid
26ºC 29ºCtemperature!
Drosophila,
mammals
birds, snakes,
butterflies
C. elegans
ants, bees, wasps
some reptiles & fish
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Sex chromosomes in humans
• XX is female, XY is male
• How is sex determined?
• Different possibilities… – 2X’s determine a female, (if not, a male)
– Y determines a male
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Sex determination in humans
• Insight into this question was gained from
syndromes with unusual #’s of sex
chromosomes
– Klinefelter syndrome: XXY
• if 2 X’s determine female - XXY would be female
• If Y determines a male, then XXY is male
– Turner syndrome: XO (1X)• if 2X determines female, then XO is male
• if Y determines male, then XO is female
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Karyotype of Klinefelter syndrome
(47,XXY)
Figure 5-5
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Karyotype of Turner syndrome
(45,X)
Figure 5-5
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Figure 5-6
What’s on the Y chromosome?
• actually ~75-90 genes on Y chromosome
sex-determining region
Y
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SRY is a region (gene) on the Y
chromosome that makes the TDF protein
• TDF: testis determining factor: specifiesmale-ness – SRY deletion in Y causes XY to be female
• SRY is necessary to be physiologically male – SRY attachment to X causes XX to be male
• SRY is sufficient to be physiologically male
• TDF is a transcription factor that is a“master switch
”that causes
“indifferentgonads” to become testes
– just the first step in development - other genesneed to be present to complete maledevelopment
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genital development is a
coordinated biochemical dance
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gender gets complicated
• XY female
• androgen-
insensitivitysyndrome
• Nikki Araguz
• can get complexlegally if people don’t
have biology
knowledge
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X-linked traits
• Males are “hemizygous”, meaning they
have only one chromosome of the pair
(one X)
• Therefore they need only 1 recessive
allele to show an X-linked trait
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Thomas Hunt MorganWas using radiation and
chemicals to cause
mutations in fruit flies,
Drosophila melanogaster .
Noticed a white-eyed
mutant male fly in 1910.
http://localhost/var/www/apps/conversion/tmp/scratch_7/0401_X_linked_inheritance.swfhttp://localhost/var/www/apps/conversion/tmp/scratch_7/0401_X_linked_inheritance.swf
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X-linked traits inherited differently
depending on gender of affected
parent
X P
F1
all F1 are red-eyed
All males have white eyes
All females have red eyes
cross A
F1
1 1:
X P
cross B
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X-linkage in Drosophila
Thomas H. Morgan’s numbers
for F2’s
Continued to see difference inF2 depending on sex of
original P parents
The F1 generation was
different depending on the
gender of the parents.
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Color-blindness in humans
is usually an X-linked trait
• What number do you see below?
– 3
– 8 – nothing
8% of males are color blind,
0.5% of females are color blind
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Pedigree for an X-linked recessive trait
(like color blindness)
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Characteristics of an X-linked
recessive trait• mostly in males
– affected allele came from mother
• often goes from mother to son
– affected mothers pass trait to all of their sons• never father to son
• affected males have: – all daughters who are carriers
– no sons who are affected (unless mother was alsoa carrier)
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Hemophilia: another X-linked
trait• Defect in blood clotting factor
– 80% of cases caused by defect in factor VIII
bleedingblood
clot
factor VIII
enzyme
hemophilia
X X
(a condition of easy bleeding)
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Pedigree nomenclature for
carriers of trait
1 2
1 2 3 4 5
6
Exhibits the trait
Carries the trait
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Hemophilia: trait that passed
through royal families
Hemophilia: bleeding disorder that can cause death
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Clinical Question:
Duchenne muscular dystrophy is
caused by a recessive X-linked allele. A man with this disorder:
1) could have inherited it from either parent.
2) must have inherited it from his mother.
3) must have inherited it from both parents.
4) would pass it along to all of his children.5) would pass it along to only his sons.
M t h th di
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Match the pedigree
to the mode of inheritance
1 2
1 2 3 4 5 6
1 2
1 2 3 4 5 6
1 2
1 2 3 4 5 6
1 2
1 2 3 4 5 6
? Autosomal recessive
? Autosomal dominant
? X-linked dominant
? X-linked recessive
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Figure 4-13
Sex-limited inheritance
• autosomal gene affects trait – trait ONLY expressed in one sex
• cock feathering
Genotype Female Male
HHHen-
feathered
Hen-
feathered
HhHen-
feathered
Hen-
feathered
hhHen-
feathered
Cock-
feathered
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Sex-influenced inheritance
• autosomal gene affects trait
– trait expressed to a lesser degree in one
sex: e.g. baldness
Genotype Female Male
BB Bald Bald
Bb Not bald Bald
bb Not bald Not bald
Figure 4-14
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Sex-influenced inheritance
• autosomal gene affects trait
– trait expressed to a lesser degree in one
sex: e.g. baldness
O ll i h it
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Organelle inheritance
(e.g. mitochrondrial inheritance)
• In addition to DNA in the nucleus, there is alsoDNA in the mitochondria
• How are mitochondria inherited?
– remember gametogenesis difference
nuclear genome
mitochondrial genome
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Example of mitochondrial
mutation in humans
• Myoclonic epilepsy and ragged-red fiber
disease (MERRF)
Children of affected mothers have trait
Children of affected fathers do not
Defects in muscle cells of MERRF patients
Translation defect in
mitochondria
Characteristics of
mitochondrial mutations
How do organisms deal with the
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How do organisms deal with the
difference in chromosome #
between males and females?
• Do females express twice as much
gene product from X-linked genes?
Dosage compensation addresses this problem
femalemale
NO
Dosage compensation: how to
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Dosage compensation: how to
deal with different “doses”of
X?• Different solutions to this problem!
XX XO
XX XYXX or XX XY
Worms express 1/2 as
much X in hermaphrodites
Flies express twice asmuch X in males
Humans
“inactivate” one X
in females
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inactivated
X chromosome
Figure 5-7
Humans “inactivate” one X
chromosome• Silence one female X chromosome so
males and females express the same
amount
• X-inactivation: causes “Barr body”
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X inactivation follows N-1 rule
• N is # of X chromosomes
– # of Barr bodies is N-1
Figure 5-8
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Lyon hypothesis
• Mary Lyon discovered X-inactivation in1961
It is random which X chromosomeis inactivated: maternal or paternal
X-inactivation occurs early in
embryonic development.
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X-inactivation is maintained
through several cell divisions• Creates “clones” or groups of cells that
have one chromosome inactivated
maternal paternal this tissue onlyexpresses
maternal X
chromosome
this tissue only
expresses
paternal X
chromosome
Result is mosaic expression
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Female cat coloration: due to X
inactivation• Which X chromosome is inactivated is
random: paternal or maternal
• Coloration
– tortoiseshell
Dinah
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X inactivation
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Maternal effect
• Offspring’s phenotype is under the control
of nuclear gene products present in the
egg
• Genotype of female parent, NOT the
genotype of the offspring determines the
phenotype of the offspring
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Maternal effect example
• Pigmentation in Ephestia (meal moth)Brown
Red
Brown BrownRed Red
RedBrown Brown Brown
Brown
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Brown
Red
Brown BrownRed Red
RedBrown Brown Brown
An enzyme was left over in the oocytes from mom.
This is sufficient to make pigment for the larvae.
The adults eventually become red-eyed and paleas we would expect.
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Other genetic terms:
Penetrance & Expressivity
• Penetrance
– The percentage of individuals that show atleast some degree of expression of a mutantphenotype.
– e.g. If 15% of mutant flies show the wild-typeappearance, the mutant gene is said to have
a penetrance of 85%.
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Other genetic terms:
Penetrance & Expressivity
• Expressivity
– The range of expression of a mutantphenotype.
– e.g. Flies homozygous for the recessivemutant eyeless gene yield phenotypes thatrange from having normal eyes to partial
reduction in size of eyes to having no eyes atall.
P t th % f l ti
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Penetrance: the % of population
that expresses the phenotype
eyeless
mutation
wild-type
or “normal”
small eyes
no eyes
15%
40%
45%
Mutant gene has a penetrance of 85%
Expressivity: same mutation
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Expressivity: same mutation
can cause a range of
phenotypesnormal eyes
small eyes
no eyes
eyeless
mutation
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Incomplete penetrance of a mutation
can alter Mendelian ratios
• Not all animals with the mutation show the
phenotype
• If mutations are incompletely penetrant, this can
alter Mendelian ratios• For example, if a recessive mutation (h) is 50%
penetrant when homozygous, a monohybrid
cross could give this ratio in the F2
– 7/8 wildtype (1/4 HH, 1/2 Hh, 1/8 hh)
– 1/8 mutant (hh)
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Conditional mutations
• The phenotype of a mutation candepend on environmental conditions
– e.g. temperature-sensitive mutations (ts)
Enzyme that produces
pigment is only functional at
the lower temperatures of
the extremities.
Epigenetics
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Epigenetics
• An epigenetic trait is a stable, mitotically,
and meiotically heritable phenotype that
results from changes in gene expression
without alterations in the DNA sequence
• Epigenetics is the study of the ways in
which these changes alter cell- and tissue-
specific patterns of gene expression.
Epigenetic Alterations to the
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Epigenetic Alterations to the
Genome
• There are three major epigeneticmechanisms:
– Reversible modification of DNA by
addition/removal of methyl groups – Alteration of chromatin by addition/removal of
chemical groups to histone proteins
– Regulation of gene expression by small,noncoding RNA molecules
ST Figure 1-2
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HistoneModification
andChromatin
Configuration
ST Figure 1-4
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MicroRNAs
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MicroRNAs
• In addition to DNA methylation and histonemodification, small, noncoding RNA molecules
called microRNAs (miRNAs) also participate
in epigenetic regulation of gene expression.
– Involved in controlling the pattern of developing
embryos and in the timing of developmental
events and physiological processes such as cell
signaling – Also play roles in the development of
cardiovascular disease and cancer
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Genomic imprinting
• Diploids have pairs of homologous
chromosomes
– usually genes are expressed from both
chromosomes – sometimes genes are only expressed on
chromosome from one parent or the other:
imprinting
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Igf2 gene
• Insulin-like growth factor ( Igf2 )
• Igf2 is important for normal growth.
• If mouse inherits normal Igf2 genes,
mouse is normally sized.
• If mouse inherits mutant Igf2 from mom,
mouse is normally sized.
• If mouse inherits mutant igf2 from dad,
mouse is “dwarf .”
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Igf2 gene
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E i ti d th E i t
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Epigenetics and the Environment
• Environmental agents, including nutrition,chemicals, and physical factors such astemperature, can alter gene expression by
affecting the epigenetic state of thegenome.
• There is indirect evidence that changes innutrition and exposure to agents that affect
the developing fetus can have detrimentaleffects during adulthood.
E i ti d th E i t
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Epigenetics and the Environment
• Women pregnant during the 1944 –1945famine in the Netherlands had children withincreased risk of obesity, diabetes, andcoronary heart disease.
– As adults, these individuals had significantlyincreased risks for schizophrenia and otherneuropsychiatric disorders.
• The F2
generation also had abnormalpatterns of weight gain and growth.
• Similar results were found in adult children ofChinese women pregnant during the 1959 –
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