genetics wk3ppt ejd

8/9/2019 Genetics WK3PPT ejd

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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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