Transcript A Mendelian Worldview

Molecular Biology
Genetics = Information Flow
Transmission Genetics =
Classical Genetics =
information flow between
generations
Molecular Biology =
Molecular Genetics =
information flow within
cells/organisms
DNA RNA  Protein =
THE CENTRAL DOGMA
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Data of Goss (1824)
pea plant from
green seed
X
pea plant from
yellow seed
All seeds yellow – grow and
self fertilize
Some pods with all Many pods with both
yellow and green seeds
green seeds
Self fertilization of
plants grown from green
All progeny plants
Have pods with
green seeds only
Some pods with all
yellow seeds –
grow into plants and
self fertilize
Some pods with all seeds
yellow, some with green
and yellow seeds
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Data of Mendel (1866)
pea plant from
green seed
X
pea plant from
yellow seed
First filial (F1) All seeds yellow Grow into plants and self fertilize
generation
second filial(F2) Count # of green and yellow seeds:
generation
-8023 total seeds
-6022 yellow
-2001 green – grown into plants: self fertilization yields
all green seeds
Take 519 yellow seeds – grown into plants: self fertilization
Of these 519 plants, 166 bred true (all yellow seeds), 353 did not
(mixed yellow and green seeds)
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Mendel’s model
True breeding yellow
AA
True breeding green
aa
egg cells
fertilize
A
F1
x
Aa (yellow seeds) – grow into plants and self fertilize
A
F2
pollen cells
a
A
AA
a
aA
(eggs)
a (pollen)
3:1 yellow:green
Aa __________________
¼ true breeding yellow
aa ½ “impure” yellow
¼ true breeding green
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Mendel’s First Law
Each trait is governed by 2 particles*, one inherited from each
parent. These two particles do not influence each other
in any way within an individual, but separate, uncontaminated
in any way, into gametes at the time of reproductive cell
Formation. (an unstated corollary is that any pollen cell can
fertilize any egg cell = random fertilization).
Testing the law:
- the test cross (Aa x aa) predicts new ratios
- other traits tested
*Introduce modern terms:
dominant, recessive, alleles, phenotype, genotype, heterozygote,
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homozygote
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Results of all Mendel's crosses in which parents differed for one character
Parental phenotype
F1
F2
F2 ratio
1 . Round X wrinkled seeds
All round
5474 round; 1850 wrinkled
2.96:1
2. Yellow X green seeds
All yellow
6022 yellow; 2001 green
3.01:1
3. Purple X white petals
All purple
705 purple; 224 white
3.15:1
4. Inflated X pinched pods
All inflated
882 inflated; 299 pinched
2.95:1
5. Green X yellow pods
All green
428 green; 152 yellow
2.82:1
6. Axial X terminal flowers
All axial
651 axial; 207 terminal
3.14: 1
7. Long X short stems
All long
787 long; 277 short
2.84: 1
What happens if two character traits are followed simultaneously?
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Fig. 13.16
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Mendel’s Second Law
Second Law=The Law of Independent Assortment:
During the formation of gametes, the segregation
of alleles at one locus is independent of that of the
segregation of alleles at any other.
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Mendel’s First Law
Each trait is governed by 2 particles*, one inherited from each
parent. These two particles do not influence each other
in any way within an individual, but separate, uncontaminated
in any way, into gametes at the time of reproductive cell
Formation. (an unstated corollary is that any pollen cell can
fertilize any egg cell = random fertilization).
Mendel’s Second Law
The Law of Independent Assortment: During the formation of
gametes, the segregation of alleles at one locus is independent
of that of the segregation of alleles at any other.
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Genes’ (alleles’) eye view
of meiosis and mitosis
A / a
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A
a
chromosome (DNA) replication
during S phase prior to mitosis
A
A
a
a
A
a
A
A
a
a
mitotic metaphase
anaphase, telophase,
cytokinesis
A
a
A
a
B
A
b
a
genotype: Aa; Bb
replication
A
A
B
B
a
a
b
b
Meiosis I anaphase,
telophase, cytokinesis
Meiosis I metaphase
Meiosis I product cells
A
A
B
B
a
a
b
b
Meiosis I product cells
A
A
B
B
Meiosis II metaphase
a
a
b
b
Meiosis II metaphase
Meiosis II anaphase,
telophase, cytokinesis
Meiosis II product cells
A
AB
B
A
AB
B
a
ab
b
a
ab
b
Meiosis I product cells
A
A
b
b
Meiosis II metaphase
a
a
B
B
Meiosis II metaphase
Meiosis II anaphase,
telophase, cytokinesis
Meiosis II products cells
A
Ab
b
A
Ab
b
a
aB
B
a
aB
B
Pseudoachondroplasia phenotype
Figure 2-30
Red-eyed and white-eyed Drosophila
Figure 2-26
Eye Color Is a Sex-Linked Trait in Drosophila
female
male
female
male
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females
males
females
males
white-eyed, normal-winged female
w
m+
w
m+
x
red-eyed, miniature winged male (wild type)
w+
m
white-eyed, normal-winged males
w
m+
wild type females
w
m+
x
w+
m
for male progeny, EXPECT:
½ white-eyed, normal-winged
w
m+
½ red-eyed, miniature winged
w+
m
64% of males fell into above classes, but 36% were either wild type
Or doubly mutant !!!!!!!
genetic recombination = chromosomal crossing over
36% of chromosomes in meiosis I:
white-eyed, normal-winged males
wild type females
w
w
m+
m+
x
w+
m
36% of males are either doubly mutant or wild type :
w+
m+
w
m
Chiasmata are the sites of crossing over
Figure 4-4
Chiasmata visible in
Locusta migratoria
spermatogenesis
A synaptonemal complex
A recombination-based map of one of the chromosomes of Drosophila
Chapter 4 Opener
vermillion (v+ = red eyes, v = vermillion eyes)
crossveinless (cv+ = normal wing veins, cv = missing crossveins)
cut (c+ = normal wing margins, c = “snipped” wing margins)
v+. cv . ct
v+/v . cv/cv+ . ct/ct+
phenotype
v ..cv+ . ct+
v+ . cv . ct
v .. cv . ct+
v+ . cv+ . ct
v .. cv . ct
v+ . cv+ . ct+
v ..cv+ . ct
v+ . cv . ct+
x
# of progeny
580
592
45
40
89
94
3
5
x
v . cv+ . ct+
v/v . cv/cv . ct/ct (three point testcross)
% of progeny
40%
41%
3%
3%
6%
6%
0.2%
0.3%
recombinant
NR
NR
v,cv ; cv,ct
v,cv ; cv,ct
v,cv ; v,ct
v,cv ; v,ct
v,ct ; cv,ct
v,ct ; cv,ct
Phenotype # of progeny(T=1448)
v ..cv+ . ct+
580
v+ . cv . ct
592
v .. cv . ct+
45
v+ . cv+ . ct
40
v .. cv . ct
89
v+ . cv+ . ct+
94
v ..cv+ . ct
3
v+ . cv . ct+
5
% of progeny
~40%
~41%
~3%
~3%
~6%
~6%
~0.2%
~0.3%
recombinant
NR
NR
v,cv ; cv,ct
v,cv ; cv,ct
v,cv ; v,ct
v,cv ; v,ct
v,ct ; cv,ct
v,ct ; cv,ct
v,cv recombinants: 45 + 40 + 89 + 94 = 268 = 18.5%
v,ct recombinants: 89 + 94 + 3 + 5 = 191 = 13.2%
ct,cv recombinants: 45 + 40 + 3 + 5 = 93 = 6.4%
Aha! The genes must all be on the same chromosome! (RF’s < 50%)
v
13.2 m.u.
ct
6.4 m.u.
cv
Hmmm…why is the measured distance between v,cv (18.5m.u.) less than the sum of the
measured v,ct (13.2 m.u.) and ct,cv (6.4 m.u) distances(=19.6 m.u.)?
double recombination
phenotype
v ..cv+ . ct+
v+ . cv . ct
v .. cv . ct+
v+ . cv+ . ct
v .. cv . ct
v+ . cv+ . ct+
v ..cv+ . ct
v+ . cv . ct+
# of progeny
580
592
45
40
89
94
3
5
% of progeny
~40%
~41%
~3%
~3%
~6%
~6%
~0.2%
~0.3%
recombinant
NR
NR
v,cv ; cv,ct
v,cv ; cv,ct
v,cv ; v,ct
v,cv ; v,ct
v,ct ; cv,ct ; v,cv !!
v,ct ; cv,ct ; v,cv !!
Aha! – we now realize the smallest classes of recombinants as doubles!
v,cv recombinants: 45 + 40 + 89 + 94 + 2(3+5) = 284 = 19.6%
v,ct recombinants: 89 + 94 + 3 + 5 = 191 = 13.2%
ct,cv recombinants: 45 + 40 + 3 + 5 = 93 = 6.4%
v
13.2 m.u.
ct
6.4 m.u.
cv
Hmmm…What is the expected # of double recombinants?
A: 0.132 * 0.064 = .0084
.0084 * 1448 = 12 expected double recombinants
But… we got only 8 (3+5) Why?
A: Interference! I = 1 - coefficient of coincidence (coc = o/e) = 0.33
Genetic Mapping
Mapping genes in humans involves
determining the recombination frequency
between a gene and an anonymous
marker
Anonymous markers such as single
nucleotide polymorphisms (SNPs) can
be detected by molecular techniques.
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
New Genes Identified on the Human Y Chromosome
Testis Determining Factor (SRY)
Channel Flipping (FLP)
Catching and Throwing (BLZ-1)
Self Confidence (BLZ-2) - (note: unlinked to ability)
Preadolescent fascination with Arachinida and Reptilia (MOM-4U)
Addiction to Death and Destruction Films (T2)
Sitting on John Reading (SIT)
Selective Hearing Loss (HUH?)
Lack of Recall for Important Dates (OOPS)
Inability to Express Affection Over the Phone (ME-2)
Spitting (P2E)

• effects of
recombination
on chromosomes
within a family
• grandson inherits
chromosome regions
from all four of his
grandparents’
chromosomes
• siblings inherit different chromosome
regions from their parents
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