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/
Test 2
Thursday Nov. 17
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:

-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
-Gene mapping in other organisms
(fungi, bacteria)
- Extensions to Mendelian Genetics
- Gene mutation
- Chromosome mutation
(- Quantitative and population genetics)
B2900
Penetrance, expressivity
and G X E
PURPOSE: To provide a concise review for human cancer
risk related to low-penetrance genes and their effects on
environmental carcinogen exposure.
CONCLUSION: Sporadic cancers are caused by geneenvironment interactions rather than a dominant effect by
a specific gene or environmental exposure.
Mutation
Source of genetic variation:
Gene Mutation (Phenotypic effects)
- 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)
mutation
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
“…in an oncogene mutation, the activity of the mutant oncoprotein has been
uncoupled from its normal regulatory pathway, leading to its continuous
unregulated expression.”  tumor growth
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
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
Human
Chromosomes
Mutation
Source of genetic variation:
Gene Mutation
 - somatic, germinal
Chromosome mutations (Ch. 11)
 - structure
- number
Chromosome Mutation
(2. changes in number)
Euploidy:
variation in complete sets of
chromosomes
Aneuploidy: variation in parts of chromosome
sets
Euploidy
1x monoploid (1 set) = n
2x diploid
(2 sets) = 2n
3x triploid
4x tetraploid
5x pentaploid
polyploid (> 2 sets)
6x hexaploid
n = # chromosomes
in the gametes
Polyploids
Autopolyploids: within one species
Allopolyploids: from different, closely
related species
Polyploids
Larger
than Diploids
Polyploids
Triploids: = 3n
- problems with pairing during
meiosis
- unbalanced gametes
- usually sterile
Applications: seedless fruits, sterile fish
aquaculture
Formation of Triploids
n
= 3n
n
n
Polar
bodies
n
n
= 3n
2n
n
Triploids (3x)
Why can’t a triploid produce viable
gametes ?
Fig. 11-5
Triploids (3x)
x=1
Gametes
Triploids
Gametes
x=2
viable
or
Nonviable
Triploids
Probability (2x or x gamete) =
1
2
( )
if x = 10
x-1
Prob. = 0.002 of viable gametes
Autotetraploid
Autotetraploid
Doubling of chromosomes: 2x----> 4x
Even number of chromosomes: normal meiosis
2<---->2 segregation------> functional gametes
Origin of
Wheat
Fig. 11-10
Allopolyploid
2n = 14, n = x = 7
hybrid
2n = 28
Chromosome
sets:
n = 14
A, B, D
7
14
Triploid
7 7 7
2n = 42
x=7
n = 21
Polyploidy
Plants:
Animals:
speciation
- rare (sex determination)
- fish (salmon)
- parthenogenetic animals
123
11
22 12 12
Plant Polyploids
% Polyploids
90
80
70
60
50
40
30
30
40
50
60
70
Latitute North
80
90
Chromosome Mutation
(changes in number)
Euploidy:
variation in complete sets of
chromosomes
Aneuploidy: variation in parts of chromosome
sets
Aneuploidy
Nullisomics (2n - 2)
Monosomics (2n - 1)
Trisomics (2n + 1)
Aneuploidy
Nullisomics (2n - 2)
- lethal in diploids
- tolerated in polyploids
Monosomics (2n - 1)
- disturbs chromosome balance
- recessive lethals hemizygous
Trisomics (2n + 1)
- sex chromosomes vs autosomes
- size of chromosome
Aneuploidy
Non-disjunction:
Meiosis I
Meiosis II
Gametes
n+1 n-1
n+1 n-1
n
n
x
n - 1 ---------> 2n - 1 monosomic
n
x
n + 1 ---------> 2n + 1 trisomic
Aneuploidy
Humans: (live births)
Monosomics - XO Turner syndrome
- no known autosomes
Trisomics XXY Klinefelter sterile male
XYY fertile male ( X or Y gametes)
XXX sometimes normal
21
Down
18
Edwards
syndromes
13
Patau
G-bands
13
21
18
X
Y
Downs Births per 1000
Downs Births per 1000
25
20
15
10
5
0
20
25
30
35
40
45
Maternal Age (years)
50
Mutations Causing Death and
Disease in Humans
% of live births
Gene mutations:
1.2
Chromosome mutations:
0.61
Chromosome Mutations
(Humans)
Trisomics
XO
Triploids
Tetraploids
Others
Chromosome
abnormalities
% of spontaneous abortions
26 %
9%
9%
3%
3%
50 %
Chromosome Mutations
Comparison of euploidy with aneuploidy
Aneuploids more abnormal than euploids:
likely due to gene imbalance
Plants more tolerant than animals to
aneuploidy and polyploidy
(animal sex determination)
Summary
Mutation
Detecting
- gene
- chromosome
(structure, number)
- cytology
genetic
analysis
- phenotype
Rate of mutation - low
Mutation
- source of genetic variation
- evolutionary change
Chapter References
Recombination, linkage maps
Ch. 6
p. 148 – 165
Prob: 1-5, 7, 8, 10, 11, 14
Extensions to Mendelian Genetics
Ch. 14 p. 459 – 473 Prob: 2, 3, 4, 5, 6, 7
Chromosome Mutations
Ch. 11 p. 350 – 377 Prob: 1, 2
Mendelian Genetics
Topics:

-Transmission of DNA during cell division







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




-Gene mapping in other organisms
(fungi, bacteria)
- Extensions to Mendelian Genetics
- Gene mutation
- Chromosome mutation