Biology 2250 Principles of Genetics

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Biology 2250Principles of Genetics

• Announcements
• Lab 4 Information B2250 (Innes) webpage
• download and print before lab.
• Virtual fly log in and practice
• http//biologylab.awlonline.com/

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Quiz 3 answers

• http//webct.mun.ca8900/
• All quizzes on WebCT for Review
• Office Hours 130 230 Tue, Wed., Thr
• or by appointment 737-4754, dinnes_at_mun.ca

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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

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• Gene mapping in other organisms
• (fungi, bacteria)
• - Extensions to Mendelian Genetics
• - Gene mutation
• - Chromosome mutation
• (- Quantitative and population genetics)

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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

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Linkage Summary

• Hunting for genes (Human Diseases)
• - genetic markers DNA variation
• - co-inheritance with diseases using
  pedigree
• information
• - recombinants used to estimate linkage

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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
  

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Chapter 1 Genes, environment, organism

• Phenotype
• gene env. gene x env. gene x gene
  
• Mendelian Genetics
• Genotype Phenotype
• Dominance ?

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G x E interaction
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Extensions to Mendelian Genetics (Gene ?
Phenotype)

• 1. Dominance
• 2. Multiple alleles
• 3. Pleiotropy
• 4. Epistasis (gene interaction)
• 5. Penetrance and expressivity

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Gene interaction

• Alleles at one gene Dominance
• Different genes Epistasis

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1. Dominance

• Location of heterozygote between
• two homozygotes
• 1. Complete
• 2. No dominance
• 3. Incomplete
  (partial)
• 4. Codominance

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Homozygotes A1A1 A2A2
Heterozygote A1A2
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Incomplete Dominance
red
white
pink
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Codominance

• Human Blood Groups
• Genotype Phenotype
• AA A
• AB AB co-dominance
• BB B
• antigen protein on RBC

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Codominance

• Molecular Markers

Allele
A B
AB AA BB BB
Heterozygote distinguished from homozygotes
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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
• ---------------------------------------------

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Multiple alleles in clover
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Test for Allelism

• Possibilities
• 1. alleles for the same gene - all crosses show
• Mendelian ratios (11 31 121)
• 2. more complex inheritance (gt 1 gene)

or
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Example white, yellow, pink
Cross F1
F2 white x yellow yellow
31 yellow white white x pink
pink 31 pink white yellow x pink
pink 31 pink yellow
3 alleles w y p 6 genotypes w
w y y p p p w y w y p
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3. Pleiotropy(one gene affects gt 1 trait)

• Example Mouse
• Gene affects
• 1. coat colour ( , yellow)
• 2. survival

dark
AA Homozygous wildtype
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Yellow Parents
zzz
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Crosses

• A. x -----gt all
• B. x ---gt 1/2
  1/2
• C. x ----gt 2/3
  1/3

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Explanation

• A. AA x AA all AA
• B. AA x AYA ½ AYA , ½
  AA
• C. AYA x AYA ¼ AA ½ AYA ¼
  AYAY

1 2 1/3
2/3
dies
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Interpretation

• Gene affects both coat colour and
• survival
• 1. AY dominant to A for coat colour
• 2. AY recessive lethal for survival

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Pleiotropy

• 
  Phenotype
• Genotype coat colour survival
• A A dark
  alive
• A AY yellow
  alive
• AY AY ?
  dead

dark
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G E P
Trait 1
Pleiotropy
Gene A
Trait 2
Gene A
Epistasis
Trait
Gene B
Gene interaction
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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 ----gt AaBb x AaBb ---gt
  F2

F1 Dihybrid
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F2
Epistasis

• AaBb x AaBb
• A- B- 9/16
• A- bb 3/16
• aa B- 3/16
• aa bb 1/16

Gene A and B unlinked
4 distinct phenotypes (2 traits) (peas shape,
colour)
Epistasis Gene A and Gene B interact ?
phenotype of 1 trait
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Epistasis(BbEe X BbEe)
1.

• Labrador retriever Coat Colour (B and E genes)
• F2 Ratio Genotype Phenotype
  Ratio
• 9/16 B- E- black
  9/16
• 3/16 B- ee gold
  4/16
• 3/16 bb E- brown
  3/16
• 1/16 bb ee gold
• Gene E allows colour deposition

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Epistasis

• Allele E Allele
  B
• Golden brown
  black
• B- ee bb E-
  B- E-
• bb ee

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Epistasis(AaBb X AaBb)
2.

• Example Flower petal colour
• F2 Ratio Genotype Phenotype
  Ratio
• 9/16 A- B- Purple
  9/16
• 3/16 A- bb White
  7/16
• 3/16 aa B- White
  
• 1/16 aa bb White

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Gene B
Gene A colourless colourless
purple (white)
(white)
A-bb aaB-
A- B- aabb
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5. Penetrance and Expressivity

• Phenotype genotype, genetic background,
• and environment
• Variable Expression Penetrance
• Expressivity

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• Penetrance
• percentage of individuals that show some
  degree of expression of a mutant genotype

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Example Polydactyly (P) extra digits

• pp Pp
  PP
• normal 10 normal polydactyly
• 90 polydactyly

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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

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Same genotype
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Variable expressivity of piebald spotting in
beagles
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Summary

• - segregation and independent assortment
• can explain a variety of patterns of
• genetic variation
• Phenotype Genotype Environment
• Genetic interaction genotype, epistasis,
• genetic
  background

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Mutation

• Source of genetic variation
• Gene Mutation
• - somatic, germinal
• Chromosome mutations (Ch. 11 prob. 1, 2)
• - structure
• - number

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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

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Somatic Mutations
Petal colour Rr red rr white
Plant genotype Rr mutation Rr
rr
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Somatic mutations
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Germinal mutations
AA (blue) Aa ? self ? aa(white)
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Mutant Phenotypes

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

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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.
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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
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Gene Mutation

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

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Chromosome Mutations

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

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Chromosome Mutations

• 1. Structure Ch. 11 363 372
• 2. Number Ch. 11 p. 350 - 363

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1. Chromosome Structure

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

(lost)
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Chromosome Structure

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

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G-bands
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Paint of Chr-22
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Paint
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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

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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

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Deletion heterozygote
deletion loop
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Pseudodominance

• Deletion Heterozygote
• deletion loop b
• (pairing of a c d
• homologues)
• deletion

Phenotype b
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Deletion Mapping
Prune pn
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Structural Abnormalities

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

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Genetics of Deletions

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

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Structural Abnormalities

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

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

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

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Hemoglobin Alpha Beta Gamma ..
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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)

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

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Inversion heterozygotewith crossing over
Fig. 11-22
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Inversion Heterozygote

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

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4. Translocation

• a b c d j k g h i e
  f

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

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

normal
Corn Pollen
aborted
aborted ??
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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

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