neo-mendelian genetics after re-discovery, mendel’s postulates were applied to many genetic...
TRANSCRIPT
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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
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Alleles
• Alleles are alternate forms of the same gene,
• Wild-type allele: the allele that occurs most frequently in the population,
– ‘normal’,– usually dominant.
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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.
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Dominance(not always complete)
xcomplete
xincomplete
xcodominant
phenotypes
A1 dom. A2A2 rec. A1
A2 dom. A1A1 rec. A2
xcomplete
A2 A2 A1 A2 hybridsA1 A1
A1 A1 A2 A2
to each other
to each other
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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.
xincomplete
A2 A2 A1 A2 hybridsA1 A1
A1 and A2 are incompletely dominant in regards to each other.
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R1: red R2: white
Genotypes Phenotypes
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Phenotypic Ratio is Equal to Genotypic Ratio
Genotypes Phenotypes
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R1 R1 R1 R2 R1 R2 R2 R2
Genotype: 1:2:1
Phenotype: 3:1R2 dom R1
Genotype: 1:2:1
Phenotype: 3:1R1 dom R2
Genotype: 1:2:1
Phenotype: 1:2:1incompletelydominant
F2 Possible Ratios
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Codominance
…expression of heterozygote phenotype resulting in offspring that resemble both parents,
– both parental traits show up equally and fully in the offspring.
xcodominant
A2 A2 A1 A2 hybridsA1 A1
A1 and A2 are codominant to each other.
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CS spotted CD dotted
CS CS CD CD
P x
CS CD
F1
CS CS CD CDCS CD CS CD
F2
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codominantg: 1:2:1
p: 1:2:1
g: 1:2:1
p: 3:1 CS dom CD
CS CS CD CDCS CD CS CD
g: 1:2:1
p: 1:2:1incompletedominance
F2 Possible Ratios
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Fig. 2-20
Dominance?Incomplete Dominance?Co-Dominance?
Think about this.
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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.
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Recessive Lethal Alleles
A a
A
a
AA Aa
Aa aa
– recessive lethal allele: homozygous recessive
individuals die, heterozygous individuals live,
Modifies Ratio:
2:1 Genotypic Ratio
all wild-type
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Lethality Definitions
• Lethal phenotype: doesn’t reproduce*,
– *late onset lethal phenotypes,
• Lethal allele: expression, or lack of expression causes death.
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t: no tail
T: wild-type
TT: tailed cat Tt: no tail tt: lethal
recessive lethal?
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t: Manx
T: wild-type
TT: tail cat Tt: no tail tt: lethal
Lack of T results in death, t is recessive……t does not result in death when T is present.
what about lethality?
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Dominant Lethal Alleles
A a
A
a
AA Aa
Aa aa
– dominant lethal allele: homozygous recessive
individuals die, heterozygous individuals die,
The dominant allele is not lethal!
The recessive allele is the lethal, it acts as a dominant lethal in the heterozygote.
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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
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Huntington’s
• Neurological and movement disorder with typical onset at about age 40,
H: wild-type h: Huntington
• 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.
HH: wild-type Hh: late onset lethal
hh: lethal
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Dominant Lethal Alleles
H h
H
h
HH Hh
Hh hh
– dominant lethal allele: dominant in regards to
lethality,
H: normal
h: Huntington’s
lethality is dominant.
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Gamete Lethality1:1 ratio
• How could this happen, how would you test your hypothesis?
Tt x Tt
1/4 TT 1/4 Tt 1/4 Tt 1/4 tt
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Reciprocal Crosses
pollen lethal?
aha3-1 x wt
TT Tt
TT Tt
T t
T
T
ovule lethal?
aha3-1 x wt
TT TT
Tt Tt
T T
T
t
YES NO
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wildtype Aha3-1
Alexander’s Stain
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Pollen
Aha3
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More than Two Alleles?
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Antigens and Antibodies
Antibody: protein with the ability to bind to specific molecules...
Antigen: substance that stimulates an immune response, especially the production of antibodies. Antigens are usually proteins and/or polysaccharides.
Cell membrane
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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 co-aggulates,
• if you add a B-antibody to blood with type B antigens, the blood co-aggulates,
• There are four recognizable phenotypes,
A B AB O
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Antigens, Antibodies and Coagulation
...once the antibody binds, the molecules coagulate, or clump together.
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I = Isoagglutinogen
...a gene with three alleles,
...codes for proteins that modify plasma membrane bound, glycosylated proteins in red blood cells.
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A B O
IA
IA codes for a protein that specifically adds a N- acetylgalactosamine
IB
IB codes for a protein that adds a galactose
i (ii)
no carbohydrate
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O
ii
3 Alleles(4 phenotypes)
A
IA IA
IAi
B
IB IB
IBi
AB
IA IB
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O
ii
IA and IB are Codominant IA and IB are Dominant to i
A
IA IA
IAi
B
IB IB
IBi
AB
IA IB
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IA and IB are Codominant IA and IB are Dominant to i
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Know Genotype/Phenotype
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Bombay Phenotype
How can this be?
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An entire H substance must be present to permit the I gene product to bind a sugar.
H Substance
H gene product catalyzes this bond.
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A B O
IA
H_
ii
H_
IA
H_
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No Antigenicity
Genotype hh
IA IA
IAi
IB IB
IBi
IA IB ii
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Bombay Phenotype
How can this be?
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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.
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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.
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Epistasis
“Classes” are masked, or “underrepresented”.
Study this chart.
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Genetics: …in the News
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Penetrance
…the frequency at which individuals with a given genotype manifest a specific phenotype.
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• 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
Penetrance
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Expressivity
…the degree, or range in which a phenotype of a specific genotype is expressed.
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• range of phenotypes
• expressivity may be referred to as a percentage, or another quantifiable measure.
all the same genotype
Expressivity
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Pentrance? Expressivity?
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Pentrance? Expressivity?
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Pentrance? Expressivity?
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Pentrance? Expressivity?
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Complementation
• process by which an allele of each of two mutant genes makes up for the defect in the other gene.
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You Find Two Mutants With a Similar Phenotype
Are they the Same Genotype?
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Possible Physiology
Enzyme A
Enzyme B
Enzyme A
Enzyme B
Enzyme A
Enzyme B
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Complement
a
|
|
B
a
|
|
B
A
|
|
b
A
|
|
b
x
A
|
|
b
a
|
|
B
Two genes
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Fail to Complement
A
|
|
b
A
|
|
b
A
|
|
b
A
|
|
b
x
A
|
|
b
A
|
|
b
1 gene
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a
b
c
de
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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.