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neo-Mendelian Genetics
• After re-discovery, Mendel’s postulates were
applied to many genetic traits,
• However, some genetic data did not conform to
the expected results,
Continuous Variation
vs.
Discontinuous Variation
Alleles
• Alleles are alternate forms of the same
gene,
• Wild-type allele: the allele that occurs
most frequently in the population,
– ‘normal’,
– usually dominant.
Wild-type vs. ?
• wild-type alleles are responsible for the
most common phenotype,
• mutant alleles: contain modified genetic
information, compared to wild-type,
• mutant alleles are responsible for mutant
phenotypes.
Dominance
(not always complete)
phenotypes
A1 A1
A2 A2
A1 A1
A2 A2
A1 A2 hybrids
complete
x
complete
x
A1 dom. A2
A2 rec. A1
A2 dom. A1
A1 rec. A2
incomplete
x
to each other
codominant
x
to each other
Incomplete Dominance
…expression of heterozygote phenotype resulting in
offspring that do not resemble either parent,
– often, offspring phenotype is intermediate between
those of the parents.
A2 A2
A1 A1
incomplete
A1 A2 hybrids
x
A1 and A2 are incompletely dominant in regards to each other.
1
R:
red
Genotypes
2
R:
white
Phenotypes
Phenotypic Ratio is Equal to Genotypic Ratio
Genotypes
Phenotypes
F2 Possible Ratios
R1 R1
R2
dom
R1
R1 dom R2
incompletely
dominant
R1 R2
R1 R2 R2 R2
Genotype:
1:2:1
Phenotype:
3:1
Genotype:
1:2:1
Phenotype:
3:1
Genotype:
1:2:1
Phenotype:
1:2:1
Codominance
…expression of heterozygote phenotype resulting in
offspring that resemble both parents,
– both parental traits show up equally and fully in the
offspring.
A2 A2
A1 A1
codominant
A1 A2 hybrids
x
A1 and A2 are codominant to each other.
S
C spotted
P
D
C dotted
x
CS CS
CD CD
F1
CS CD
F2
CS CS
CS CD
CS CD
CD CD
F2 Possible Ratios
CS CS
CS CD
CS CD
CD CD
codominant
g: 1:2:1
p: 1:2:1
CS dom CD
g: 1:2:1
p: 3:1
incomplete
dominance
g: 1:2:1
p: 1:2:1
Fig. 2-20
Dominance?
Incomplete Dominance?
Co-Dominance?
Think about this.
Lethal Alleles
• Essential alleles that if not expressed in a
sufficient amount, result in lethality,
– recessive lethal allele: homozygous recessive
individuals die, heterozygous individuals live,
– dominant lethal allele: homozygous recessive
individuals die, heterozygous individuals die.
Recessive Lethal Alleles
– recessive lethal allele: homozygous recessive
individuals die, heterozygous individuals live,
A
A
AA
a
Aa
Modifies Ratio:
2:1 Genotypic Ratio
a
Aa
aa
all wild-type
Lethality Definitions
• Lethal phenotype: doesn’t reproduce*,
– *late onset lethal phenotypes,
• Lethal allele: expression, or lack of
expression causes death.
recessive
lethal?
TT: tailed cat
Tt: no tail
t: no tail
T: wild-type
tt: lethal
what about
lethality?
TT: tail cat
t: Manx
T: wild-type
Tt: no tail
tt: lethal
Lack of T results in death, t is recessive…
…t does not result in death when T is present.
Dominant Lethal Alleles
– dominant lethal allele: homozygous recessive
individuals die, heterozygous individuals die,
A
A
a
AA
Aa
a
Aa
aa
The dominant allele is
not lethal!
The recessive allele is the
lethal, it acts as a
dominant lethal in the
heterozygote.
Huntington’s Disease
It is spoken of by those in whose veins the
seeds of the disease are know to exist, with
a kind of horror, and not at all alluded to
except through dire necessity.
- George Huntington, 1872
Huntington’s
• Neurological and movement disorder with typical onset at
about age 40,
H: wild-type
HH: wild-type
h: Huntington
Hh: late onset
lethal
hh: lethal
• On March 23, 1993, the Huntington's disease gene was discovered near the tip of
chromosome 4. Discovery of the gene has led to direct, genetic testing for the
disease.
• Gene therapy and other programs are underway and are highly encouraging.
Dominant Lethal Alleles
– dominant lethal allele: dominant in regards to
lethality,
H
h
H: normal
H
HH
Hh
h
Hh
hh
h: Huntington’s
lethality is dominant.
Gamete Lethality
1:1 ratio
Tt x Tt
1/4 TT
1/4 Tt
1/4 Tt
1/4 tt
• How could this happen, how would you test your
hypothesis?
Reciprocal Crosses
aha3-1 x
wt
T
t
T
TT
Tt
T
TT
Tt
pollen lethal? YES
aha3-1 x wt
T
T
T
TT
TT
t
Tt
Tt
ovule lethal? NO
Aha3-1
wildtype
Alexander’s Stain
Pollen
Aha3
More than Two Alleles?
Antigens and Antibodies
Antigen: substance that stimulates an immune
response, especially the production of antibodies.
Antigens are usually proteins and/or polysaccharides.
Antibody: protein with the ability to bind to specific
molecules...
Cell membrane
ABO and Allelic Interactions
• ABO blood groups,
– A and B antigens are on the surface of red blood cells,
• if you add an A-antibody to blood with type A antigens, the blood coaggulates,
• if you add a B-antibody to blood with type B antigens, the blood coaggulates,
• There are four recognizable phenotypes,
A
B
AB
O
Antigens, Antibodies and Coagulation
...once the
antibody
binds, the
molecules
coagulate,
or clump
together.
I = Isoagglutinogen
...a gene with three alleles,
...codes for proteins that modify plasma
membrane bound, glycosylated proteins in
red blood cells.
A
B
A
IB
I
O
i (ii)
no carbohydrate
IA codes for a protein
that specifically adds a
N- acetylgalactosamine
IB codes for a protein
that adds a galactose
3 Alleles
(4 phenotypes)
A
IA IA
B
AB
IB IB
IA IB
IAi
O
IBi
ii
A
B
I and I are Codominant
A
B
I and I are Dominant to i
A
IA IA
B
AB
IB IB
IA IB
IAi
O
IBi
ii
A
B
I and I are Codominant
A
B
I and I are Dominant to i
Know Genotype/Phenotype
Bombay Phenotype
How can this be?
H Substance
H gene product
catalyzes this
bond.
An entire H substance
must be present to permit
the I gene product to bind
a sugar.
A
A
I
H_
B
IA
H_
O
ii
H_
No Antigenicity
Genotype hh
IA IA
IB IB
IAi
I Bi
IA IB
ii
Bombay Phenotype
How can this be?
Epistasis
…a gene interaction in which the effects of
one gene hides the effects of another gene,
– epistatic: gene A genotype hides gene B
phenotype,
– hypostatic: gene B phenotype is hidden by
gene A genoype.
ABO and H Alleles
• epistatic: hh genotype hides AB
phenotypes,
– h gene is epistatic to I gene,
• hypostatic: AB phenotypes are hidden by
hh genotypes,
– I gene is hypostatic to h gene.
Study this chart.
Epistasis
“Classes” are masked, or “underrepresented”.
Genetics:
…in the News
Penetrance
…the frequency at which individuals with a
given genotype manifest a specific
phenotype.
Penetrance
• 4 of 6 dogs, or 66%
of the population
shows the phenotype,
at some level,
• penetrance is
usually referred to as
a percentage.
all the same genotype
Expressivity
…the degree, or range in which a phenotype
of a specific genotype is expressed.
Expressivity
• range of
phenotypes
• expressivity may be
referred to as a
percentage, or
another quantifiable
measure.
all the same genotype
Pentrance? Expressivity?
Pentrance? Expressivity?
Pentrance? Expressivity?
Pentrance? Expressivity?
Complementation
• process by which an allele of each of two
mutant genes makes up for the defect in the
other gene.
You Find Two Mutants With a
Similar Phenotype
Are they the Same Genotype?
Possible Physiology
Enzyme A
Enzyme B
Enzyme A
Enzyme B
Enzyme A
Enzyme B
Complement
a
a
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B
B
x
a
A
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B
b
A
A
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b
b
Two genes
Fail to Complement
A
A
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b
b
x
A
A
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b
b
A
A
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b
b
1 gene
a
b
f
c
e
d
Assignments
• Read from Chapter 3, 3.6 (pp. 100-106),
• Master Problems…3.12, 3.15, 3.20,
• Read Chapter 4, 4- 4.4,
• Chapter 4, Problems 1, 2,
• Questions 4.1 - 4.4, 4.6, 4.7, 4.9, 4.11 -4.14, 4.19 - 4.20
a,b,c,d.