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For thousands of years we have known that traits were inherited....but how?
Scientists were unsure of the laws of inheritance
Oswald Avery
1977-1955
Gregor Johann Mendel
1822­1884
From Halifax, Ns
Augustinian monk in Austria
1944
Genes and chromosomes are made of DNA
Developed the foundation of modern genetics through his experimentation with garden peas
R strain bacteria: Removed substances. If the
bacteria still transformed, the genes were still
present. (Protein, DNA, or carbohydrates)
It was previously believed that peas showed a
blend of traits
He noticed that
they always show
one of a pair
Crossed plants with
different traits to see
offspring
Cross­pollinate (hybridize) two contrasting, true breeding pea varieties
True Breeding: All offspring have the same trait
P generation: true­breeding parents
F1 generation: hybrid offspring
F1 hybrids would self­pollinate to produce F2 generation
1
P generation: Purple­flowered plant crossed with a white­
flowered plant
r
R
r
Rr
R
R
Rr
R
r
r
F1 offspring: Purple
Self­fertilization
r
R
F2 generation: purple and white­flowered plants
R
RR
R
r
r
Rr
R
r
Purple: dominant trait
White: recessive trait
The heritable factor for white flowers was present in F1 plants. Why didn't this affect flower colour?
Regardless of the
combinations, one trait
always dominated
Mendel's hypothesis:
1. Alternative versions of genes account for variations in inherited traits
2. For each trait, an organism inherits two alleles, one from each parent
3. If the two alleles for a trait are different, then one, the dominant allele, masks the presence of the other, recessive allele, and determines the appearance of the organism.
4. Mendel’s law of segregation states that the two alleles for a trait separate during gamete production and end up in different gametes. The law of independent assortment says that the alleles segregate independent of one another.
1. Alternative versions of genes account for variations in inherited traits
Alleles: alternative versions (e.g. purple and white)
Each gene resides
at a specific locus
on a specific
chromosome
2. For each trait, an organism inherits two alleles, one from each parent
Homozygous: alleles are the same
Heterozygous: alleles are different
Phenotype: an organism's traits
Genotype: an organism's genetic makeup
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3. If the two alleles for a trait are different, then one, the dominant allele, masks the presence of the other, recessive allele, and determines the appearance of the organism.
Dominant does not mean more common...
4. Mendel’s law of segregation states that the two alleles for a trait separate during gamete production and end up in different gametes. The law of independent assortment says that the alleles segregate independent of one another.
Let's think of meiosis...
r r
R r
r r r
r
R r r
R R
r
r r
First experiments only considered 1 trait...
Monohybrids: individual that is heterozygous for
one character
Monohybrid cross: Cross between two
heterozygotes
e.g Round Seed Wrinkled Seed
e.g Round Seed Wrinkled Seed
P RR
rr
P Rr
r, r Gametes R, r Gametes R, R F1 Rr (all round) F2
Rr
R, r RR, Rr, Rr, rr (3:1)
Punnett Square
What can it show?
Genotype
Phenotype
Probability
heterozygous purple x white
p p
P Pp Pp p
pp
pp
F1: 1/2 purple, 1/2 white
Two heterozygous tall plants
T
t
T
TT
Tt
t
Tt
tt
"first filial"
"filius" and "filia" = son and daughter
Hybrids: Crosses between parents with different traits
F1: 3 tall, 1 short
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How can we tell if an individual is
homozygous or heterozygous when they show
a dominant phenotype?
Test Cross: unknown is crossed with a homozygous
recessive individual. The genotype of unknown
parent can be deduced from the appearance of the
offspring
R = round seed
b
b
? Bb
Bb
?
Bb
Bb
f
f
? Ff
Ff
?
ff
ff
r = wrinkled seed
r
r
? Rr Rr ?
Rr Rr All appear round
r
r
? Rr Rr ?
rr
rr Half appear round,
half appear wrinkled
r
r
? rr rr ?
rr rr d
ff
ff
?
ff
ff
All appear wrinkled
rr
Rr
RR
d
? A pea plant with a tall phenotype is pollinated by a short plant, and the seeds of the first generation hybrid produce 327 tall plants and 321 short plants. Give the genotypes of all the plants.
~1:1
t
Tt
Tt
t
Tt
tt
t
Tt
Tt
t
Tt
tt
2 Tt(tall), 2 (tt)
4 Tt (tall)
For Dalmatian dogs, the spotted condition is dominant to non­spotted.
a) Using a Punnett square, show a cross between two heterozygous parents.
b) A spotted female Dalmatian dog is mated to an unknown male. If the female has six pups, three spotted and three non­spotted, what are the genotype and phenotype of the unknown male?
S
s
S
s
S
SS
Ss
s
Ss
ss
s
Ss
ss
s
Ss
ss
t
T
T
T
The allele that causes albinism (p) is recessive to the allele for normal pigmentation (P). A normal woman whose father is an albino marries an albino man whose parents are both normal. They have three children, two normal, one albino. Give the genotype for each individual.
P
p
1:1 pups
p
p
In horses, the trotter characteristic is dominant to the pacer characteristic. A male trotter mates with three different females, and each female produces a foal. The first female, a pacer, gives birth to a foal that is a pacer. The second female, also a pacer, gives birth to a foal that is a trotter. The third female, a trotter, gives birth to a foal that is a pacer. Determine the genotypes of the male, all three females, and the three foals sired.
1
3
2
T
t
t
Tt
tt
t
tt
tt
T
t
t
Tt
tt
t
tt
tt
T
t
T
TT
Tt
t
Tt
tt
Pp
Pp
Pp
pp
In fruit flies, straight wings is dominant over curly. Show how you would determine if a straight winged fly were heterozygous or homozygous?
Test cross
s
s
s
s
S
?
S ?
Ss
Ss
S
?
Ss
Ss
Ss
Ss
s ?
ss
ss
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Alleles segregate during the formation of gametes. Mendel wondered if they did so independently. He considered two traits at once ­ a dihybrid cross (two­factor cross)
yellow seeds (Y)
rryy
green seeds (y)
Do traits travel together, or are they inherited separately?
round seeds (R) wrinkled seeds (r)
E.g. Does the gene that determines whether a seed is round or wrinkled have anything to do with its seed colour?
ry ry
ry
ry
ry
ry
ry
ry
rryy
a
ry
If they do exhibit independent assortment
ry
RY
ry
ry
RY
RY
OR
RY RY
RY
RY
RRYY
RRYY
RY
RY
RY
RY
If they don't exhibit independent assortment
If they do exhibit independent assortment
RY
Which one should we use ?
rryy
F1
ry
ry
If they do exhibit independent assortment
ry
RrYy
F2
ry
RY
RrYy
RrYy
RrYy
RrYy
RY
RrYy
RrYy
RrYy
RrYy
RY
RY RrYy
RrYy
RrYy
RrYy
RY RrYy
RrYy
RrYy
RrYy
rY
ry
RY
RrYy
RRYY
Ry
If they do exhibit independent assortment
Ry
rY
ry
If they don't exhibit independent assortment
If they do exhibit independent assortment
The F2 offspring: two phenotypes yellow + round (dominant)
green + wrinkled (recessive)
3:1 ratio
(just like a monohybrid cross)
3 dominant:1 recessive
If the alleles separated independent of one another, how many combinations should we observe? e.g. Four different kind of sperm and four different kinds of eggs should give 16 different combinations in the offspring
F2 generation: 9:3:3:1
Which one is correct?
This showed that traits are inherited independently
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Mendelian inheritance is governed by the laws of probability
0
no chance
1
occur every time
P = # correct outcomes
# total outcomes
Independent events: If the outcome of one event does not have an effect on the outcome of future events
e.g. The chance of getting heads in a coin toss is 1/2. The chance of getting heads a second time is still 1/2.
What is the probability of tossing heads?
What is the probability of rolling a 1 on a six sided die?
What is the probability of rolling any other number?
r
R RR Rr
What is the probability of obtaining a heterozygote?
R
http://nature.ca/genome/04/041/0414_e.cfm
r
Rr rr
Rule of multiplication: used to determine the chance that two or more independent events will occur together in some specific combination
1. Calculate the probability of each independent event.
2. Multiply the individual probabilities to obtain the overall probability of these events occurring together.
e.g. The probability that two coins tossed at the same time will each land heads up
1/2 x 1/2 = 1/4
This also applies to dihybrid crosses
Probability of a heterozygous parent producing a homozygous dominant gamete.
YyRr
YR
1/2 x 1/2 = 1/4
What is the probability that heterozygous parents will have an offspring with the genotype YYRR?
e.g. The probability that a heterozygous plant will self­fertilize to produce a white flowered offspring.
(The chance that a sperm with a white allele will fertilize an other with a white allele)
Pp
pp
1/2 x 1/2 = 1/4
YR ovum = 1/4
YR sperm = 1/4
1/4 x 1/4 = 1/16
Rule of addition: The chance of either one of two possible outcomes occurring = the sum of the two individual probabilities.
e.g. F1 gametes can form a heterozygote by two different ways
1. Dominant comes from sperm, recessive from ovum 1/4
2. Dominant from ovum, recessive from sperm 1/4
1/4 + 1/4 = 2/4 or 1/2
Beyond Dominant and Recessive Alleles
Not all traits follow the simple rules of Mendelian inheritance
Some alleles show different degrees of dominance and recessiveness in relation to each other
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Codominance
Both alleles are expressed an affect the phenotype
Heterozygous phenotype: Blend of two homozygous phenotypes
e.g. Heterozygous chickens: "erminette" colouring (speckled black and white feathers)
e.g Heterozygous four o'clocks (flowers): pink (red and white)
e.g. Roan cattle: red bull x white cow (reddish in colour but have white and red hairs)
1:2:1 is characteristic of codominance
AABBCC = very dark
aabbcc = very light
Incomplete Dominance
Phenotype is also a blend of both alleles
Who feels like this....?
Cross between heterozygotes: 3 phenotypes
Phenotype from mother, Phenotype from father, Blended phenotype
e.g. Snapdragons
White flowered plant x red flowered plant
F1: all pink offspring
F2 (self­pollination): 1:2:1 (red, pink, pink, white)
1:2:1
Characteristic of incomplete dominance
15. A geneticist notes that crossing a round shaped radish with a long shaped radish produces oval shape radishes. If oval radishes are crossed with oval radishes, the following phenotypes are noted: 100 long, 200 oval, and 100 round radishes. For the cross between a pure­breeding round and a pure­breeding long radish, use symbols to show the F1 and F2 generations.
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Multiple Alleles
Genes that more than two alleles exist
* Even if more than 2 alleles exits, each individual only possesses 2 (one from each parent)
Full color (C), albino (c), light­gray or chinchilla (cch) and white with black points or a Himalayan (ch). Full color is dominant to all the other alleles. Chinchilla is dominant to Himalayan. Albino is recessive to all.
Epistasis: one gene affects the phenotypic expression of a separate gene
E.g. Mice: coat color depends on two genes.
Epistatic gene: determines whether pigment will be deposited in hair or not
Presence (C) is dominant to absence (c) of pigment
The second gene: colour of the pigment (black (B) or brown (b))
ch
ch
chc , c c
An individual that is cc has a white (albino) coat regardless of the genotype of the second gene
Polygenic Inheritance: Some traits appear to be distributed across a spectrum
"having many genes"
17. Palomino horses are known to be caused by the interaction of two different genes. The allele Cr in the homozygous condition produces a chestnut, or reddish color, horse. The allele Cm produces a very pale cream color, called cremello, in the homozygous condition. The palomino color is caused by the interaction of both the chestnut and cremello alleles. Indicate the expected ratios in the F1 generation from mating a palomino with a cremello.
e.g. skin color and height
Skin color in humans is controlled by many independent genes
Multiple alleles control the coat color of rabbits. A gray color is produced by the dominant allele C. The Cch allele produces a silver­gray color when present in the homozygous condition, CchCch, called chinchilla. When Cch is present with a recessive gene, a light silver­gray color is produced. The allele Ch is recessive to both the full color allele and the chinchilla allele. The Ch allele produces a white color with black extremities. This coloration pattern is called Himalayan. An allele Ca is recessive to all the other alleles. The Ca allele results in a lack of pigment, called albino. The dominance hierarchy is C > Cch > Ch > Ca. The table below provides the possible genotypes and phenotypes for coat color in rabbits. Notice that four genotypes are possible for full color but only one for albino.
a) Indicate the genotypes and phenotypes of the F1 generation from the mating of a heterozygous Himalayan coat rabbit with an albino coat rabbit.
Phenotypes Genotypes Full color CC, CCch, CCh, CCa
b) The mating of a full color rabbit with a light gray Chinchilla CchCch
rabbit produces two full color offspring, one light Light gray CchCh, CchCa
gray offspring, and one albino offspring. Indicate the Himalaya ChCh, ChCa
genotypes of the parents.
Albino CaCa
c) A chinchilla color rabbit is mated with a light gray rabbit. The breeder knows that the light grey rabbit had an albino mother. Indicate the genotypes and phenotypes of the F1 generation from this mating.
d) A test cross is performed with light gray rabbit, and the following offspring are noted: five Himalayan color rabbits and five light gray rabbits. Indicate the genotype of the light­gray rabbit.
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22. Flower color in certain plants displays epistasis. P= purple p= white, C= curved petals c= straight petals. A homozygous recessive petal shape prevents purple color. If parent plants are Ppcc x PPCc, what is the genotypic and phenotypic ratios of the offspring?
23 In mice, the gene C causes pigment to be produced, while the recessive gene c makes it impossible to produce pigment. Individuals without pigment are albino. Another gene, B, located on a different chromosome, causes a chemical reaction with the pigment and produces a black coat color. The recessive gene, b, causes an incomplete breakdown of the pigment, and a tan, or light­brown, color is produced. The genes that produce black or tan coat color rely on the gene C, which produces pigment, but are independent of it. Indicate the phenotypes of the parents and provide the genotypic and phenotypic ratios of the F1 generation from the following crosses:
a) CCBB x Ccbb (b) ccBB x CcBb (c) CcBb x ccbb (d) CcBb x CcBb
What is a pedigree?
A diagram of family relationships
Used to map inheritance of genetic diseases
Individuals with the trait are usually shaded in
Oldest individual is at the top of the page
B: brown (dominant over all)
b: blue (recessive over all)
Marriages
G: green (dominant over g and b)
g: blue (recessive over all)
Females
Males
Assume DOMINANT:
24. Use the phenotype chart (pedigree) to answer the following questions.
a) How many children do the parents A and B have?
b) Indicate the genotypes of the parents.
c) Give the genotypes of M and N.
A
Male
normal
Male
diabetic
D
C
Is it possible that these pedigrees are for the dominant trait?
B
E
G
F
H
? ? Female
normal
Female
diabetic
I
J
K
L
M
N
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Assume RECESSIVE:
Assume RECESSIVE:
Is it possible that this pedigree is for the recessive trait?
Is it possible that these pedigrees are for the recessive trait?
25. For the family outlined below, draw a pedigree
a) Generation I : A male with blood type O marries a female with blood type A.
b) Generation II : They have 4 children. The first born is a male with A type blood, the second born is a girl with O type blood, and the last two children were identical twin boys.
c) Generation III : The last boy married a woman with type B blood. They had two girls, one with AB blood type and one with B blood type.
Genetic disorders and Mendelian Inheritance
Recessively inherited disorder: homozygous recessive (ex. ii)
Genes code for proteins
Heterozygotes may not show the phenotypic effects; however, they are carriers!
a
A
A
a
Allele that causes genetic disorder:
Non­functional protein or no protein
Homozygous dominant: Normal phenotype
Heterozygous: Normal phenotype (one copy of allele is sufficient)
Homozygous recessive: Disease phenotype (Unable to produce enough protein)
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What if an allele is rare?
Are all harmful alleles recessive?
Unlikely that you will meet and mate with someone who also carries the allele.
NO!
Some are dominant!
Unless inbreeding occurs (ex. royalty)
Mating between relatives increases the risk
Ex. Austrian Lip
This is why many societies have laws/taboos forbidding inbreeding
Some disorders are lethal far before reproductive age; therefore, no homozygous recessives will reproduce
We can sometimes assess the risk that a genetic
disorder will occur before conception or in early
pregnancy
Genetic Counselling
Carrier Recognition: identify possible carriers
DNA Fingerprinting
Embryonic screening (ethical?)
Affected embryos destroyed
Unaffected embryos implanted
What if fetal tests reveal a serious disorder?
Moral Dilemma
Lethal dominant alleles are rare: homozygous
dominants AND heterozygotes are affected (die)
If lethal before reproductive age: will not be passed
on (will only be show if it acts late)
in utero testing
Amniocentesis (14th to 16th week of pregnancy)
Amniotic fluid:
Fluid tested for particular alleles, chemicals present
Karyotyping of cells in fluid (can take several weeks)
Chorionic villus sampling (CVS) (8th to 10th week of pregnancy)
Karyotyping: fetal tissue removed from placenta
The cells are growing very quickly (can take as little as 24h)
Ultrasound and fetoscopy (assess fetal health)
Why do we veer against amniocentesis and fetoscopy?
Maternal bleeding, fetal death (1%)
Only used for cases where there is a high risk of a genetic disorder or
birth defect
What about X­linked disorders?
XA = normal
Xa = the trait (a genetic disease or abnormality)
Y = Y chromosome (males only)
Terminate pregnancy
or
Care for a child with a
genetic disorder
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Is it possible that this pedigree is for an X­linked recessive trait?
Is it possible that this pedigree is for an X­linked recessive trait?
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