Mendelian Genetics

1
Mendelian Genetics

• Topics
• -Transmission of DNA during cell division
• Mitosis and Meiosis
• - Segregation
• - Sex linkage
• - Inheritance and probability
• - Mendelian genetics in humans
• - Independent Assortment
• - Linkage
• - Gene mapping
• - 3 point test cross

?
?
?
?
?
- Tetrad Analysis (mapping in fungi) -
Extensions to Mendelian Genetics - Gene
mutation - Chromosome mutation
?
?
?
?
?
?
2
Dates

• Friday Nov. 12 Tuesday 900 am lecture
  review
• Quiz 3 Tuesday Nov. 16

3
Mutation

• Source of genetic variation
• Gene Mutation
• - somatic, germinal
• Chromosome mutations (Ch. 11)
• - structure
• - number

4
Mutation

• Gene Mutation
• a------gta Forward mutation
• a ------gta Reverse mutation
• 1. Somatic mutation
• - not transmitted to progeny
• 2. Germinal Mutation
• - transmitted to next generation

5
Somatic Mutations
Petal colour Rr red rr white
Plant genotype Rr mutation Rr
rr
6
(No Transcript)
7
Somatic mutations
8
Germinal mutations
AA (blue) Aa ? self ? aa(white)
9
Mutant Phenotypes

• Morphological
• Lethal
• Biochemical
• Resistance
• Conditional - DTS (David T. Suzuki)
• (permissive and restrictive
  conditions)

10
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.
11
Gene Mutation

• Mutations are rare and random
• Ultimate source of genetic variation
• Cancer Proto-oncogene ?oncogene ? cancer
• mutation

12
Chromosome Mutations

• Gene mutation detected
  genetically
• Chromosome Mutations detected genetically and
• 
  cytologically
• 1. Structure
• 2. Number

13
1. Chromosome Structure

• Karyotype
• 1. size and number
• 2. centromere position
• telocentric
• acrocentric
• metacentric
• submetacentric
• acentric

(lost)
14
Chromosome Structure

• 3. Heterochromatin pattern
• - heterochromatin (dark)
• - euchromatin (light)
• 4. Banding patterns
• a) staining Giemsa bands
• b) polytene chromosomes (flies)

15
G-bands
16
Paint of Chr-22
17
Paint
18
Structural Abnormalities

• Normal a b c d e f
• 1. Deletion a c d e f
• 2. Duplication a b b c d e f
• 3. Inversion a e d c b f
• 4. Translocation
• a b c d j k g h i
  e f

19
Structural Abnormalities

• 1. Deletions
• deletion homozygote----gtusually lethal
• deletion heterozygote----gt viable
• deletion loop b
• (pairing of a c d
• homologues) a c d
• deletion

20
Deletion heterozygote
deletion loop
21
Deletion Mapping
Prune pn
22
Structural Abnormalities

• Deletion notch-wing (Drosophila)
• Phenotype
• Genotype wing survival
• N N normal alive
• N N notch alive
• N N - dead
• 
  (recessive lethal)

23
Genetics of Deletions

• Reduced map distance ( chromosome shortened)
• Recessive lethal
• Deletion loop (detected during meiosis)

24
Structural Abnormalities

• 2. Duplications
• tandem duplication
• a b b c d
• maintain original evolve new
• function function

25
Unequal crossing over
deletion
Tandem duplication
26
Bar Eye Mutation (Dominant)
27
Gene Duplication and Evolution

• Gene duplication - Evolution of new function
• Example Hemoglobin genes - duplication
• Express in different stages
• embryo fetus adult

28
Structural Abnormalities

• 3. Inversions - different gene order
• - usually viable
• a b c d e f a b e d c f a b e d
  c f
• a b c d e f a b c d e f a b e d
  c f
• homozygote heterozygote homozygote
• N N N I
  I I
• normal (N) inversion (I)

29
Cytological consequences of an Inversion Heterozyg
ote Inversion Loop
a b c d e
a d c b e
Fig. 11-21
crossover
X
Inversion Loop
30

• Cytological consequences of an Inversion
• Heterozygote Inversion Loop
• Cross-over within an inversion
• dicentric bridge (broken)
• acentric fragment (lost)
• deletions

31
Inversion heterozygotewith crossing over
Fig. 11-22
32
Inversion Heterozygote

• Reduced recombination frequency
• (suppression of crossing over)
• Semisterile

33
4. Translocation

• a b c d j k g h i e
  f

Translocation Heterozygote (meiosis)
N2
N1
T2
T1
34
Translocation
35
Fig. 11-24
Translocation heterozygote
36
Translocation heterozygoteAdjacent segregation
T1
N2
N1
T2
inviable
37
Translocation heterozygoteAlternate segregation
N1
N2
T1
T2
viable
38
Translocation

• Change linkage relationships
• (position effects)
• Change chromosome size
• Semisterile - unbalanced meiotic products

normal
Corn Pollen
aborted
aborted ??
39
Structural Abnormalities

• Normal a b c d e f
• 1. Deletion a c d e f
• 2. Duplication a b b c d e f
• 3. Inversion a e d c b f
• 4. Translocation
• a b c d j k g h i
  e f

40
(No Transcript)
41
Chromosome Mutation(2. changes in number)

• Euploidy variation in complete sets of
• chromosomes
• Aneuploidy variation in parts of chromosome
• sets

42
Euploidy

• 1x monoploid (1 set) n
• 2x diploid (2 sets) 2n
• 3x triploid
• 4x tetraploid
• 5x pentaploid polyploid (gt 3 sets)
• 6x hexaploid
• n chromosomes
  in the
• gametes

43
Polyploids

• Autopolyploids within one species
• Allopolyploids from different, closely
• related species

44
Polyploids Larger than Diploids
45
Polyploids

• Triploids 3n
• - problems with pairing
  during
• meiosis
• - unbalanced gametes
• - usually sterile
• Applications seedless fruits, sterile fish
• 
  aquaculture

46
Formation of Triploids
n
3n
n
n
Polar bodies
3n
n
2n
n
n
47
Triploids (3x)

• Why cant a triploid produce viable gametes ?

48
Fig. 11-5
49
Triploids (3x)
Gametes

• x 1

50
Triploids
Gametes

• x 2

viable
or
Non- viable
51
Triploids

• Probability (2x or x gamete)
• ( )
• if x 10 Prob. 0.002 of viable gametes

x - 1
1
2
52
Autotetraploid

• Doubling of chromosomes 2x----gt 4x
• Even number of chromosomes normal meiosis
• 2lt----gt2 segregation------gt functional gametes

53
Origin of WheatFig. 11-10
2n 14, n x 7
hybrid
2n 28 n 14
Chromosome sets A, B, D 7 7 7
7
14
Triploid
2n 42 x 7 n 21
54
Polyploidy

• Plants speciation
• Animals - rare (sex determination)
• - fish (salmon)
• - parthenogenetic animals

123 11 22 12 12
55
Plant Polyploids
56
Chromosome Mutation(changes in number)

• Euploidy variation in complete sets of
• chromosomes
• Aneuploidy variation in parts of chromosome
• sets

57
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

58
(No Transcript)
59
(No Transcript)
60
Aneuploidy

• Non-disjunction Gametes
• Meiosis I n 1 n - 1
• Meiosis II n 1 n - 1
  n
• n x n - 1 ---------gt 2n - 1
  monosomic
• n x n 1 ---------gt 2n 1
  trisomic

61
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

62
G-bands
13
18
21
X
Y
63
Downs Births per 1000
64
(No Transcript)
65
Mutations Causing Death and Disease in Humans

• of live births
• Gene mutations 1.2
• Chromosome mutations 0.61

66
Chromosome Mutations(Humans)

• of spontaneous
  abortions
• Trisomics 26
• XO 9
• Triploids 9
• Tetraploids 3
• Others 3
• Chromosome 50
• abnormalities

67
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)

68
Summary

• Mutation - gene
• - chromosome
• (structure, number)
• Detecting - cytology
• - phenotype
• Rate of mutation - low
• Mutation - source of genetic variation
• - evolutionary change

genetic analysis