Biology 2250
Principles of Genetics
Announcements
Lab 4 Information: B2250 (Innes) webpage
download and print before lab.
Virtual fly: log in and practice
http://biologylab.awlonline.com/
Quiz – 3 answers
http://webct.mun.ca:8900/
All quizzes on WebCT for Review
Office Hours: 1:30 – 2:30 Tue, Wed., Thr
or by appointment: 737-4754, dinnes@mun.ca
Mendelian Genetics
Topics:
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-Transmission of DNA during cell division
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Mitosis and Meiosis
- Segregation
- Sex linkage (problem: how to get a white-eyed female)
- Inheritance and probability
- Independent Assortment
- Mendelian genetics in humans
- Linkage
- Gene mapping
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-Gene mapping in other organisms
(fungi, bacteria)
- Extensions to Mendelian Genetics
- Gene mutation
- Chromosome mutation
(- Quantitative and population genetics)
Linkage: Summary
• Recombination: generates new combinations
(inter and intrachromosomal)
• Genetic maps:
- genes linked on the same chromosome
- location of new genes relative to genes
already mapped
Linkage: Summary
• Hunting for genes (Human Diseases)
- genetic markers: DNA variation
- co-inheritance with diseases using pedigree
information
- recombinants used to estimate linkage
Extensions to Mendelian Genetics
Ch. 14 From Gene to Phenotype
Readings: Ch. 14 p. 454 – 473
Problems: Ch. 14: 2, 3, 4, 5, 6, 7
Chapter 1
Genes, environment, organism
Phenotype =
gene + env. + gene x env. + gene x gene
Mendelian Genetics:
Genotype
Phenotype
Dominance ?
G x E interaction
Extensions to Mendelian
Genetics
(Gene  Phenotype)
1. Dominance
2. Multiple alleles
3. Pleiotropy
4. Epistasis (gene interaction)
5. Penetrance and expressivity
Gene interaction
1. Alleles at one gene
Dominance
2. Different genes
Epistasis
1. Dominance
Location of heterozygote between
two homozygotes
1. Complete
2. No dominance
3. Incomplete (partial)
4. Codominance
Homozygotes: A1A1 A2A2
Heterozygote: A1A2
Incomplete Dominance
red
white
pink
Codominance
Human Blood Groups:
Genotype
Phenotype**
AA
A
AB
AB co-dominance
BB
B
** antigen protein on RBC
Codominance
Molecular Markers
Allele
A
B
AB
AA
BB
BB
Heterozygote distinguished from homozygotes
2. Multiple Alleles
(ABO Blood groups - 3 alleles)
Genotype
Phenotype
(6)
(4)
--------------------------------------------OO
O
recessive
AA, AO
A
dominant
BB, BO
B
dominant
AB
AB co-dominant
---------------------------------------------
Multiple alleles
in clover
Test for Allelism
Possibilities:
or
1. alleles for the same gene - all crosses show
Mendelian ratios (1:1 3:1 1:2:1)
2. more complex inheritance (> 1 gene)
Example: white, yellow, pink
Cross
white x yellow
white x pink
yellow x pink
F1
yellow
pink
pink
3 alleles: w y
p
6 genotypes: w w y y p p
F2
3:1 yellow : white
3:1 pink : white
3:1 pink : yellow
pw
yw
yp
3. Pleiotropy
(one gene affects > 1 trait)
Example: Mouse
Gene affects:
1. coat colour (
2. survival
AA
Homozygous wildtype
dark
, yellow)
zzz
Yellow
Parents
Crosses
A.
x
-----> all
B.
x
---> 1/2
1/2
C.
x
----> 2/3
1/3
Explanation
A. AA
B. AA
x
AA
all AA
x AYA
C. AYA x AYA
½ AYA , ½ AA
¼ AA ½ AYA ¼ AYAY
1
1/3
:
2
2/3
dies
Interpretation
Gene affects both coat colour and
survival
1. AY dominant to A for coat colour
2. AY recessive lethal for survival
Pleiotropy
Genotype
AA
A AY
AY AY
Phenotype
coat colour
survival
dark
dark
yellow
?
alive
alive
dead
G
+
E =
P
Trait 1
Pleiotropy
Gene A
Trait 2
Epistasis
Gene A
Trait
Gene B
Gene interaction
4. Epistasis
(gene interaction)
More than one gene affects a character
One gene pair masks or modifies the
expression of another gene pair
AABB
x aabb ----> AaBb x AaBb ---> F2
F1
Dihybrid
Epistasis
AaBb
Gene A and B
unlinked
x
AaBb
F2 A- B- 9/16
A- bb 3/16
aa B- 3/16
aa bb 1/16
4 distinct
phenotypes (2 traits)
(peas: shape, colour)
Epistasis: Gene A and Gene B interact  phenotype of 1 trait
1.
Epistasis
(BbEe X BbEe)
Labrador retriever Coat Colour (B and E genes)
F2 Ratio
9/16
3/16
3/16
1/16
Genotype Phenotype
B- Eblack
B- ee
gold
bb Ebrown
bb ee
gold
Gene E allows colour deposition
Ratio
9/16
4/16
3/16
Epistasis
Allele E
Allele B
Golden
brown
B- ee
bb ee
bb E-
black
B- E-
2.
Epistasis
(AaBb X AaBb)
Example: Flower petal colour
F2 Ratio
9/16
3/16
3/16
1/16
Genotype
A- BA- bb
aa Baa bb
Phenotype
Purple
White
White
White
Ratio
9/16
7/16
Gene B
colourless
(white)
A-bb
aabb
Gene A
colourless
(white)
purple
aaB-
A- B-
5. Penetrance and Expressivity
Phenotype: genotype, genetic background,
and environment
Variable Expression:
Penetrance
Expressivity
Penetrance:
percentage of individuals that show some
degree of expression of a mutant genotype
Example: Polydactyly (P)
extra digits
pp
normal
Pp
PP
10 % normal polydactyly
90 % polydactyly
Expressivity:
degree that a given genotype is expressed
phenotypically
Example: Pp individuals which do express
the extra digits can vary
(a) extra digit on each hand and foot
(b) extra digit on one hand only
(c) complete digit or vestige
Same
genotype
Variable expressivity of
piebald spotting in beagles
Summary
- segregation and independent assortment
can explain a variety of patterns of
genetic variation
- Phenotype = Genotype + Environment
Genetic interaction: genotype, epistasis,
genetic background
Mutation
Source of genetic variation:
Gene Mutation
- somatic, germinal
Chromosome mutations (Ch. 11 prob. 1, 2)
- structure
- number
Mutation
Gene Mutation
a+------>a Forward mutation
a ------>a+ Reverse mutation
1. Somatic mutation
- not transmitted to progeny
2. Germinal Mutation
- transmitted to next generation
Somatic Mutations
Petal colour:
Rr red
rr white
Plant genotype: Rr
mutation: Rr
rr
Somatic mutations
Germinal mutations
AA (blue)
Aa  self  aa(white)
Mutant Phenotypes
Morphological
Lethal
Biochemical
Resistance
Conditional - DTS (David T. Suzuki)
(permissive and restrictive conditions)
Mutation Frequency
Drosophila eye-colour w+  w 4 x 10-5 per gamete
Humans
Hemophilia (X-linked recessive) 4 x 10-5 per gamete
(1 in 25,000)
“It is estimated that up to 30% of cases of hemophilia
have no known family history. Many of these cases are the
result of new mutations. This means that hemophilia can
affect any family.”
Mutation Frequency
Drosophila eye-colour w+  w 4 x 10-5 per gamete
Mutation rate for a particular gene: very low (efficient repair)
but,
Large number of genes in a genome: mutations occur every
generation
4 x 10-5 x 50,000 genes = 2 mutations
Gene Mutation
Mutations are rare and random
Ultimate source of genetic variation
Cancer: Proto-oncogene oncogene  cancer
mutation
Chromosome Mutations
Gene mutation:
detected genetically
Chromosome Mutations: detected genetically and
cytologically
1. Structure
2. Number
Chromosome Mutations
1. Structure Ch. 11 363 – 372
2. Number Ch. 11 p. 350 - 363
1. Chromosome Structure
Karyotype:
1. size and number
2. centromere position:
telocentric
acrocentric
metacentric
submetacentric
acentric
(lost)
Chromosome Structure
3. Heterochromatin pattern
- heterochromatin (dark)
- euchromatin (light)
4. Banding patterns:
a) staining Giemsa bands
b) polytene chromosomes (flies)
G-bands
Paint of Chr-22
“Paint”
Structural Abnormalities
Normal
1. Deletion
a b c d e f
a c d e f
2. Duplication a b b c
d e f
3. Inversion
c b f
a e d
4. Translocation
a b c d j k
g h
i e f
Structural Abnormalities
1. Deletions:
deletion homozygote---->usually lethal
deletion heterozygote----> viable
deletion loop
(pairing of
homologues)
b
a
a
c
c
d
d
deletion
Deletion heterozygote
deletion loop
Pseudodominance
Deletion Heterozygote:
deletion loop
(pairing of
homologues)
Phenotype:
b
a
+
c
+
d
+
deletion
+ b + +
Deletion Mapping
Prune
pn
Structural Abnormalities
Deletion: notch-wing (Drosophila)
Phenotype
Genotype
wing
survival
N+ N+
normal
alive
N+ N
notch
alive
N N
dead
(recessive lethal)
Genetics of Deletions
• Reduced map distance ( chromosome
shortened)
• Recessive lethal
• Deletion loop (detected during meiosis)
Structural Abnormalities
2. Duplications:
tandem duplication
a b b c d
maintain original
function
evolve new
function
Unequal crossing over
deletion
Tandem duplication
Bar Eye Mutation (Dominant)
Gene Duplication
and Evolution
Gene duplication - Evolution of new function
Example: Hemoglobin genes - duplication
Express in different stages:
embryo – fetus – adult
Hemoglobin:
Alpha
Beta
Gamma
………..
Structural Abnormalities
3. Inversions - different gene order
- usually viable
abcdef
abcdef
homozygote
NN
abedcf
abedcf
abcdef
abedcf
heterozygote homozygote
NI
II
normal (N)
inversion (I)
Cytological consequences of an Inversion
Heterozygote: Inversion Loop
Fig. 11-21
a
b
c
d
e
a
d
c
b
e
crossover
X
Inversion Loop
Cytological consequences of an Inversion
Heterozygote: Inversion Loop
Cross-over within an inversion
dicentric bridge (broken)
acentric fragment (lost)
deletions
Inversion
heterozygote
with crossing
over
Fig. 11-22
Inversion Heterozygote
• Reduced recombination frequency
(suppression of crossing over)
• Semisterile
4. Translocation
a b c
d j k
g h i e f
Translocation Heterozygote (meiosis)
N1
N2
T1
T2
Translocation
Translocation
heterozygote
Fig. 11-24
Translocation heterozygote
Adjacent segregation
T1
N2
N1
T2
inviable
Translocation heterozygote
Alternate segregation
N1
N2
T1
T2
viable
Translocation
Change linkage relationships
(position effects)
Change chromosome size
Semisterile - unbalanced meiotic products
normal
Corn Pollen
aborted
% aborted = ??
Structural Abnormalities
Normal
1. Deletion
a b c d e f
a c d e f
2. Duplication a b b c
d e f
3. Inversion
c b f
a e d
4. Translocation
a b c d j k
g h
i e f