Download Mendel`s Principles of Heredity

Lecture 2
Mendel’s Breakthrough
Mendel’s Principles of
Heredity
Patterns, Particles, and
Principles of Heredity
ᯘ⩶ె ⪁ᖌ
http://lms.ls.ntou.edu.tw/course/136
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O tli off M
Outline
Mendelian
d li G
Genetics
ti
The historical puzzle of inheritance
• Part 1:
• Artificial selection has been an important
practice since before recorded history.
• The historical puzzle of inheritance
• Part 2:
• Domestication of animals
• Selective breeding of plants
• Mendel’s approach to genetic analysis
including
g his experiments
p
and related
analytic tools
• 19th century – precise techniques for
controlled matings in plants and animals
to produce desired traits in many
offspring
• Part 3:
• A comprehensive example of Mendelian
inheritance in humans
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The historical puzzle of inheritance
•
Breeders could not
explain why traits would
sometimes disappear and
then reappear in
subsequent generations
generations.
•
What causes the
similarities
i il iti and
d
differences of appearance
and the skipping of
generations?
Historical theories of inheritance
• One parent contributes
most features (e.g.,
homunculus, N. Hartsoiker
1694).
1694)
Nicolaas Hartsoeker
was a Dutch
mathematician and
physicist who invented
the screw-barrel simple
microscope
Fig 2
Fig.
2.1
1
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• Blending inheritance –
parental traits become
mixed and forever
changed in offspring
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Gregor Mendel
St t off genetics
State
ti iin early
l 1800’
1800’s
What is inherited?
How is it inherited?
What is the role of chance
in heredity?
abbot Cyril Napp
• Moravian Sheep Breeder and
govern of the Monaster in Brno
• Encourage Mendel to study the
phenomenon of hybridization
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(1822-1884)
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• 1822 Born
• Childhood Gardener, studying bee keeping
• 1840-1843
1840 1843 Univ
Univ. of Olomouc
Olomouc, studying
physics and pholosophy
• 1843 Augustinian
g
Abbey
y of St. Thomas in
Brno
• 1851 Study in University of Vienna
• 1853 As a Teacher in his Abbey
• 1866 Published “Versuche über Pflanzenhybriden”
• 1867 As abbot of the monastery
• 1884 die from chronic nephritis
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M d l’ work
Mendel’s
k
K
Keys
tto M
Mendel’s
d l’ experiments
i
t
• The
Th garden
d pea was an ideal
id l organism.
i
•
•
•
•
Vigorous growth
Self fertilization (the petals of flower close down tightly)
Easy to cross fertilize
Produced large number of offspring each generation
• The first scientist to combine data collection, analysis,
y
and
theory to understand heredity
• He inferred genetic laws about the appearance and
di
disappearance
off traits
t it during
d i diff
differentt generations
ti
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Keys to the success of Mendel
Mendel䇻
䇻s experiments
P i i l off Hybridization
Principle
H b idi ti
P re breeding lines of peas (Pis
Pure-breeding
(Pisum
m sati
sativum)
m)
• Breeding could be done by cross-fertilization or selfing
• Large numbers of progeny produced within a short time
• Traits remained constant in crosses within a line
Inheritance of alternative forms of traits
• Antagonistic pairs of "either-or" traits: e.g. purple or white,
yellow or g
y
green,, Round vs. wrinkled seeds,, Long
g vs. short
stem length (not continuous traits)
Brilliant experimentalist
p
• Planned experiments carefully
• Controlled the plant breeding
• Analyzed results mathematically
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We could learn more from Mendel
as a scientist
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Partt 1
• Reciprocal crosses
You should have learned….
•The background of Mendel’s life
•Keys for his success
•Why pea is a good experiment model?
•How to become a great scientist as
Mendel?
• Everything counted
• Practical experimentalist
• Simplified
p
as “black-and-white”
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Mendel studied seven antagonistic
pairs of traits in peas
Th
Themes
off M
Mendel’s
d l’ work
k
Note that each hybrid resembles only one of
the p
parents: the dominant trait
• Variation is widespread in nature.
• Observable variation is essential for
following genes
genes.
• Variation is inherited according to
genetic
ti llaws and
d nott solely
l l b
by chance.
h
Mendel’s
s laws apply to all sexually
• Mendel
reproducing organisms.
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Mendel proposed that each plant carries
two copies of a unit of inheritance
Monohybrid crosses reveal units of
inheritance and Law of Segregation.
Mendel crossed pure
purebreeding lines that differed
in only one trait, e.g. seed
color
Examined p
phenotypes
yp of F1
progeny and F2 progeny
• F1 progeny have only one
of the parental traits
• Both parental traits
reappear in F2 progeny in
a 3:1 ratio
Th
These
results
lt di
disproved
d th
the
blending hypothesis
Traits have two forms that can each breed true
• Trait that appears
pp
in F1 p
progeny
g y is the dominant form
• Trait that is hidden in the F1 progeny is the recessive
form
• Progeny inherit one unit from the maternal parent and
the other unit from the paternal parent
One year
Units of inheritance are now known as "genes"
• Alternative forms of a single gene are "alleles"
alleles
• Individuals with two different alleles for a single trait
are "monohybrids”
Huge number
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The Punnett square is a simple
way to visualize the segregation
and random union of alleles
Mendel's
Mendel
s law of segregation
The two alleles for each trait
separate
t d
during
i
gamete
t
formation
Fig. 2.10a
Each F1 hybrid produces two
kinds of gametes in a 1:1
ratio
Two gametes, one from each
parent,
t unite
it att random
d
att
fertilization
F2 progeny
• 3:1 ratio of phenotypes
• 1/4 will breed true for
the dominant trait
• 1/2 will
ill b
be h
hybrids
b id
• 1/4 will breed true for
the recessive
recessi e trait
Fig. 2.10b
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Fig. 2.11
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Mendel's results and the Punnett square
reflect the basic rules of probability
P b bilit and
Probability
dM
Mendel’s
d l’ R
Results
lt
Product rule (independent events): probability of two independent
events occurring together is the product of their individual
p
probabilities
• Cross Yy xYy pea plants.
• Chance of Y pollen uniting with a Y ovule
• What is the probability that event 1 AND event 2 will occur?
• Solution = determine p
probabilityy of each and multiply
p y them together.
g
• P(1 and 2) = probability of event 1 X probability of event 2
• ½ chance of pollen with Y allele
• ½ chance
h
off ovule
l with
ith Y allele
ll l
• Chance of Y and Y uniting = ½ x ½ = ¼
• Chance of Yy offspring
Sum rule (Mutually exclusive events): probability of either of two
mutually exclusive events occurring is the sum of their individual
probabilities
• What is the probability that event 1 OR event 2 will occur?
• Solution
S
= determine the probability off each and add them together.
• P(1 or 2) = probability of event 1 + probability of event 2
• ½ chance of pollen with y allele and ovule with Y allele
• ½ chance of p
pollen with Y allele and ovule with y allele
• Chance of Yy = (½ x ½) + (½ x ½) = 2/4, or 1/2
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Mendel did further crosses to verify
y
the law of segregation
G
Genotypes
t
and
d Phenotypes
Ph
t
F2 plants were selfed to produce F3 progeny
• All of the green F2 peas were pure breeding
• Phenotype
Ph
t
• Observable characteristic of an organism
• Any
A observable
b
bl characteristic
h
t i ti or ttrait
it off an
organism: such as its morphology, development,
physiological
y
g
p
properties,
p
, or
biochemical or p
behavior.
• 1/3 of the yellow F2 peas were pure breeding
• 2/3 of the yellow F2 peas were hybrids
• Genotype
• Pair of alleles present in an individual
• The genetic constitution of a cell, an organism, or
an individual
i di id l (i
(i.e. th
the specific
ifi allele
ll l makeup
k
off th
the
individual) usually with reference to a specific
character under consideration
Fig. 2.12
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Genotype vs phenotype in
homozygotes and heterozygotes
H
Homozygous
and
d Heterzygous
H t
• Homozygous – two alleles of trait are the
same (YY or yy)
• Heterozygous – two alleles of trait are
different (Yy)
F
From
a cross off Yy
Y x Yy
Y peas
•
The heterozygous phenotype defines the dominant allele
((e.g.
g Yy
yp
peas are yyellow,, so the yellow
y
Y allele is
dominant to the green y allele
•
A dominant allele with a dash represents an unknown
genotype
t
(e.g.
(
Y stands
Y
t d for
f either
ith YY or Yy)
Y )
yp in F2 p
progeny
g y are
Genotypes
in 1:2:1 ratio (1/4 YY, 1/2 Yy,
1/4 yy)
Phenotypes in F2 progeny
are in 3:1 ratio (3/4 yellow,
1/4 green)
Fig. 2.13
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Mendel's dihybrid crosses revealed the
law of independent assortment
Testcross reveal unknown genotype
Mendel tested whether two genes in dihybrids would
segregate independently
Is the genotype of an individual with a dominant phenotype
(e.g. Y) heterozygous (Yy) or homozygous (YY)?
First,
Fi
t he
h crossed
d ttrue-breeding
b di
yellow
ll
round
d peas with
ith
true-breeding green wrinkled peas to obtain dihybrid F1
plants:
YY RR x yy rr Æ F1 Yy Rr
Then the dihybrid F1 plants were selfed to obtain F2 plants:
Then,
F1 Yy Rr x F1 Yy Rr Æ F2
• Solution: Testcross to homozygous recessive
(yy) and examine progeny
Fig. 2.14
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Mendel asked whether all the F2 progeny would be
parental types (yellow round and green wrinkled) or
would
ld some b
be recombinant
bi
t ttypes (yellow
( ll
wrinkled
i kl d and
d
green round)?
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A dihybrid cross produces parental
types and recombinant types
R
Results
lt off M
Mendels
d l dih
dihybrid
b id crosses
Each F1 dihybrid produces four
possible gametes in a
1:1:1:1 ratio
Yy Rr Æ 1/4 Y R, 1/4 Y r,
1/4 y R, 1/4 y r
• F2 generation contained both parental
types and recombinant types.
independently,
• Alleles of genes assort independently
and can thus appear in any combination
in the offspring
offspring.
Four phenotypic classes
occurred in the F2 progeny:
• Two are like parents
• Two are recombinant
Fig. 2.15
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Independent assortment in crosses of F1
dihybrids produces a 9:3:3:1 phenotype ratio
Note that
N
h iin these
h
F2 progeny, there
h
iis a 3
3:1
1 phenotype
h
ratio of dominant to recessive forms
Mendel's
M d l' llaw off iindependent
d
d t assortment
t
t
During gamete formation,
different pairs of alleles
segregate
t
independently of each
other
• Y is just as likely to
assort with R as it is
with r
• y is just as likely to
assort with R as it is
with
ith r
Fig. 2.15
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Fi 2
Fig.
2.16
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Following crosses with branchedbranched-line diagrams
Testcrosses on
dihybrids
Progeny phenotypes for each gene are shown in different
columns
This gives the same ratios as seen in the Punnett square
in Fig 2.15
Testcross dihybrids
to individuals that
are homozygous for
both recessive traits
Fi 2
Fig.
2.17
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Fig. 2.18
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Mendel's laws can be used to predict
offspring from complicated crosses
Predicting proportions of progeny
from multihybrid crosses – example 1
To calculate the possible number of gamete genotypes
from a hybrid, raise 2 to the power of the number of
different traits
Cross Aa Bb Cc Dd x Aa Bb Cc Dd
What proportion of progeny will be AA bb Cc Dd?
• Aa x Aa Æ 1/4 AA
• Bb x Bb Æ 1/4 bb
• Cc x Cc Æ 1/4 Cc
• Dd x Dd Æ 1/4 Dd
• Aa Bb Cc Dd Æ 24 = 16 kinds of gametes
• Aa Bb Cc Dd x Aa Bb Cc Dd Æ 16 x 16 = 256 genotypes
• To do a Punnett square with this cross involving four
f
genes, you would need 16 columns and 16 rows
So, the expected proportion of AA bb Cc DD progeny is:
1/4 x 1/4 x 1/2 x 1/2 = 1/64
• An easier way is to break down a multihybrid cross into
independently assorting monohybrid crosses
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Predicting proportions of progeny
from multihybrid crosses – example 2
Wh t Mendel
What
M d l did nott know
k
Cross Aa Bb Cc Dd x Aa Bb Cc Dd
• Trait is controlled by genes, which
encodes
e
codes p
proteins
oe s
• Why pea shape different?
How many
yp
progeny
g y will show the dominant traits for A,, C,,
and D and the recessive trait for B?
• Aa x Aa Æ 3/4 A
• ““rr”” encodes
d a mutant
t t SBE1 (starch( t h
branching enzyme 1)
• Bb x Bb Æ 1/4 bb
• Cc
C x Cc
C Æ 3/4 C
C
• Dd x Dd Æ 3/4 D
So, expected proportion of A bb C D progeny is:
3/4 x 1/4 x 3/4 x 3/4 = 27/256
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The science of genetics began
with the rediscovery of Mendel's work
Summary
S
off Mendel's
M d l' work
k
• Inheritance is particulate - not blending.
• There
Th
are ttwo copies
i off each
h ttrait
it iin a germ
cell.
• Gametes
G
t contain
t i one copy off the
th trait.
t it
• Alleles (different forms of the trait) segregate
randomly.
d l
• Alleles are dominant or recessive - thus the
diff
difference
b
between
t
genotype
t
and
d phenotype.
h
t
• Different traits assort independently.
Mendel published his monumental breakthrough in understanding
heredity in 1866, but hardly anyone paid attention to his work!
In 1900, three scientists independently rediscovered and
acknowledged Mendel's work
Fig. 2.19
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Mendelian inheritance in humans
E d off Part2
End
P t2
Many heritable traits in humans are caused by interaction of
multiple genes and so don't show simple Mendelian
inheritance patterns
You should have learned…
• What is Mendel's law of segregation?
• What is law of independent assortment?
• Use Punnett square and Probability
calculation.
• Genetic jargons: allele,
allele testcross,
testcross F1….
F1
In 2009, there were ~ 4300 single-gene traits known in
humans
• See Table 2.1 for some of the common single-gene traits
Even with single
single-gene
gene traits
traits, determining inheritance
pattern in humans can be tricky
• Long generation time
• Small numbers of progeny
• No controlled matings
• No pure-breeding lines
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Some of the most common singlesingle-gene traits
caused by recessive alleles in humans
Disease
Effect
Incidence of Disease
Thallassemia
((chromosome 16 or 11))
Reduced amounts of
g
anemia, bone, and
hemoglobin;
spleen enlargement
1/10 in parts of Italy
Sickle-cell anemia
(chromosome 11)
Abnormal hemoglobin; sickleshaped red cells, anemia,
blocked circulation; increased
resistance to malaria
1/625 AfricanAmericans
Cystic fibrosis
((chromosome
h
7)
Defective cell membrane protein;
excessive
i mucus production;
d ti
digestive and respiratory failure
1/2000 Caucasians
Tay-Sachs disease
(chromosome 15)
Missing enzyme; buildup of fatty
deposit in brain; buildup disrupts
mental development
1/3000 Eastern
European Jews
Phenylketonuria (PKU)
(chromosome 12)
Missing enzyme; mental
deficiency
1/10,000 Caucasians
Some of the most common singlesingle-gene traits
y dominant alleles in humans
caused by
Disease
Effect
Incidence of Disease
Hypercholesterolemia
(chromosome 19)
Missing protein that removes
cholesterol from the blood; heart
attack by age 50
1/122 French
Canadians
Huntington disease
( h
(chromosome
4)
Progressive mental and
neurological
l i l damage;
d
neurologic
l i
disorders by ages 40 - 70
1/25,000 Caucasians
Table 2.1
Table 2.1
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C ti Fib
Cystic
Fibrosis
i
H ti t
Huntington
di
disease
• First reported by George
H ti t iin 1872
Huntington
• Neurological disorder, jerky body
movement
• No cure….
• Polyglutamine diseases
• Respiratory and
digestive malfunction
• Usually die before 30
• CFTR chloride channel
(cystic fibrosis transmembrane
conductance regulator)
George Huntington
• CAG repeat in Huntington gene
(HTT)
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In humans we must use pedigrees to study
inheritance.
Symbols used in pedigree analysis
• Pedigrees are an orderly diagram of a
families relevant genetic features extending
through multiple generations
generations.
• P
Pedigrees
di
h
help
l us iinfer
f if a ttrait
it is
i ffrom a
single gene and if the trait is dominant or
recessive.
i
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How to Recognize Dominant and
Recessive Traits in Pedigrees?
A vertical pattern of inheritance
indicates a rare dominant trait.
• Dominant Traits
• Affected children always have at least one
affected parent.
• As a result, dominant traits show a vertical
pattern of inheritance: the trait shows up in
every generation
ti
• Two affected parents can produce
unaffected
naffected children
children, if both parents are
heterozygotes
Huntington’s disease: A rare dominant trait
Assign the genotypes by working backward through the pedigree
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How to Recognize Dominant and
Recessive Traits in Pedigrees?
A horizontal pattern of inheritance
indicates a rare recessive trait.
• Recessive Traits
• Aff
Affected
t d individuals
i di id l can b
be th
the children
hild
off two
t
unaffected carriers, particularly as a result of
g
matings.
g
consanguineous
• All the children of two affected parents should be
affected.
• Rare recessive traits show a horizontal pattern of
inheritance.
• Recessive traits may show a vertical pattern of
inheritance if the trait is extremely common in
population.
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Cystic fibrosis: a recessive condition
Assign the genotypes for each pedigree
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G
Genetics
ti and
d society
i t
G
Genetic
ti discrimination
di
i i ti
• M
May 21
21, 2008 - The
Th P
President
id
Bush signed into law the
G
Genetic
ti Information
I f
ti
Nondiscrimination Act (GINA)
th t will
that
ill protect
t t Americans
A
i
against discrimination based
on their
th i genetic
ti iinformation
f
ti
when it comes to health
i
insurance
and
d employment.
l
t
• Eddy Curry fought for his
genetic rights!
• Do you support “Genetic Screening”?
• Good for what?
• 1970~ USA sickle-cell anemia screening project
• 1980~ Ferrara, Italy, E-thalassemia screening
• Problem of g
genetic screening
g
• Who gets benefit? Individual or society?
• Accuracy?
• Optional?
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Eddy Curry, NBA player
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E d off P
End
Partt 3
E d off the
End
th class
l
You should have learned…
• The cause of human genetic diseases
• How to read and use Pedigree
• The ethical issues related to genetics
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Ask yourself…..
• What are Mendel’s Law?
• How to apply “sum
sum rule”
rule and “product
product
rule” in genetic calculation?
• How to use a Pedigree to determine a
recessive or dominant mutant in
human?
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