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Epigenetics The emerging field of epigenetics proposes that

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Title: Epigenetics The emerging field of epigenetics proposes that


1
Chapter 15The Chromosomal Theory of Inheritance
2
1860s Mendels work - Genetics 1880
Mitosis Cytology, Flemming 1890 Meiosis
Cytology, Van Beneden 1900 Rediscovery of
Mendels work Genetics 1902 Cytology and
Genetics converge - Sutton
3
1902 Cytology and Genetics come together
  • Similarities between Mendels factors and the
    behavior of chromosomes
  • Chromosomes and genes are both paired in diploid
    cells
  • Homologous chromosomes separate and allele pairs
    segregate during meiosis
  • Fertilization restores the paired condition for
    both chromosomes and genes

4
The Chromosome Theory of Inheritance
  • Mendelian factors or genes are located on
    chromosomes
  • It is the chromosomes that segregate and
    independently assort
  • Thomas Hunt Morgan provided convincing evidence

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Drosophila Melanogaster
  • Morgans choice of organism was the fruit fly
  • because they are
  • easily cultured,
  • prolific breeders,
  • have a short generation time and
  • have only 4 pairs of chromosomes (easily visible)

7
Thomas Hunt Morgan in the Fly Lab
8
Drosophila Have 4 pairs of Chromosomes
9
http//www.news.cornell.edu/releases/March01/fly_e
ar.hrs.html
10
Some Mutations
11
Morgan Traced a Gene to a Specific Chromosome
  • Provided convincing evidence that Mendels
    inheritable factors are located on chromosomes.

12
Morgans genetic symbols are now convention. A
genes symbol is based on the first mutant
discovered Wild type trait is designated by a
. w white eye allele Cy curly
wing w wild type allele Cy wild
type If the mutant is recessive, the letter is
lower case If the mutant is dominant, the letter
is capitalized Wild type is not always dominant
13
Discovery of Sex Linkage
  • After a year of breeding to find mutant flies,
    Morgan discovered a single male fly with white
    eyes.
  • He mated this white-eyed male with a red-eyed
    (normal or wild type) female.

14
F1 generation
  • All had red eyes, suggesting the wild- type was
    dominant over the mutant.
  • Thus, the F2 generation should exhibit the 31
    phenotypic ratio.

15
F2 Generation
  • 31 (red to white) ratio seen, however
  • All females were red-eyed
  • Only males were white-eyed
  • Whats going on?
  • Morgan deduced that eye color is linked to sex
    and the gene for eye color is located on the X
    chromosome.

16
Morgan and Linked Traits
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Sex Linked Traits
  • Eye color is linked to sex and the gene must be
    on the X chromosome.
  • Females carry 2 copies, males 1
  • If mutant allele is recessive, white eyed female
    has the trait on both Xs.
  • White eyed male cannot hide the trait since he
    has only one X.

19
  • Who is responsible when a boy inherits a X linked
    condition?
  • The mother (father only contributes Y).
  • A carrier of the condition is heterozygous for
    the trait, so only females can carry sex linked
    traits.

20
Linked Genes
  • Linked genes are located on the same chromosome
    and tend to be inherited together, they do NOT
    assort independently.
  • A dihybrid cross of linked genes will NOT give
    the F2 ratio of 9331.

21
  • In flies gray body(b) is dominant to black body
    (b), and long wings (vg) are dominant to
    vestigial wings (vg).
  • What is the expected phenotypic ratio from a
    cross between a heterozygous gray, heterozygous
    normal winged fly with a black vestigial fly?

22
  • b black body vg vestigial winged
  • b gray body vg wild type wings
  • bb vgvg X bb vgvg (test
    cross)
  • gray, normal black, vestigial
  • Morgan expected a 1111 ratio,
  • he did not get it.

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  • What explains the non-Mendelian results?
  • There was NO independent assortment!
  • The traits are linked on the same chromosome.

25
  • If the traits are linked, then all of the
    offspring should resemble the parental types,
    black vestigial or gray normal.
  • How did we get the recombinant traits of black
    normal and gray vestigial?

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  • When half the progeny are recombinants, there is
    a 50 frequency of recombination
  • A 50 frequency usually indicates that the genes
    are on different chromosomes as this is the
    expected result for random assortment.
  • If the genes in the previous cross were
    completely linked, a 11 of parental only
    phenotypes would occur.

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Using Recombination Frequency to Map Traits
  • Recombination frequency between black and
    vestigial traits is 17
  • Recombination frequency between cn and black is
    9
  • Recombination between cn and vg is 9.5
  • Map these traits on the chromosome.

33
A Linkage Map
34
  • Determine the order of genes along a chromosome
    based on the following recombination frequencies
  • A - B 8
  • A - C 28
  • A - D 25
  • B - C 20
  • B - D 33

35
D A B C

8
28
25
20
33
36
A Partial Genetic Map
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Sex-Linked Traits in Humans
  • Color blindness
  • Duchenne muscular dystrophy
  • Hemophilia
  • Far more males than females have these disorders
  • Males are said to be hemizygous (one copy of a
    gene in a diploid organism)

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X Inactivation in Females
  • How does an organism compensate for the fact that
    some individuals have a double dosage of
    sex-linked genes, while others have only one?
  • X inactivation , the inactive X condenses into a
    Barr body
  • The inactivation is random and approximately half
    the Xs from Mom and half the Xs from Dad will
    inactivate

42
X-inactivation and Calico Cats
43
  • The calico cat is the result of multiple alleles
    on the X chromosome combined with X inactivation.
  • One allele causes orange fur and the other causes
    black fur.
  • The male cat will be either orange or black.
  • Only a heterozygous female will be calico with
    regions that are orange and regions that are
    black based on the X inactivation.

44
Errors and Exceptions
  • Alterations of chromosome number
  • Anuploidy, abnormal of chromosomes
  • trisomy 21 Down syndrome
  • trisomy 13 Patau syndrome
  • trisomy 18 Edwards syndrome
  • Polyploidy, more than two complete sets
  • triploidy 3n
  • tetraploidy 4n
  • nondisjunction, mitosis without cytokinesis

45
Sex Chromosome Anuploidies
  • Less severe conditions because few genes on Y and
    X inactivation.
  • Single Y maleness
  • Lack of Y femaleness

46
  • XO Turner Syndrome - only viable monosomy
    (female, short, lack mature female sex organs,
    sterile)
  • XXY Kleinfelter Syndrome (male, sterile,
    some feminization) also XXXY, XXXXY and XXXXXY
  • XXX metafemale (variable effects, fertile)
  • XYY tall male, fertile, many show no other
    effects.

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Alterations of Chromosome Structure
  • Deletion
  • Duplication
  • Translocation
  • Inversion
  • Non-reciprocal / unequal crossing over

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Normal Human Karyotype
52
Cancer Cell Chromosomes
53
Fragile X
Fragile X syndrome is the most common genetically
inherited form of mental retardation
54
Genomic Imprinting
  • Certain genes are imprinted in some way in each
    generation
  • Phenotypic effect of a particular allele depends
    on which parent the allele was from
  • Old imprints are erased in each generation when
    sperm and ova are produced

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Example of Genomic Imprinting
  • Deletion of a particular segment of Chrom 15
  • can lead to either
  • Prader-Willi syndrome (mental retardation,
    obesity, small hands and feet) if the allele is
    from the father, or
  • Angelman syndrome (uncontrollable laughter,
    jerky movements, mental and motor symptoms) if
    the allele is from the mother.

58
Epigenetics
The study of factors that control genes
  • The emerging field of epigenetics proposes
    that there is a "second code" of programming on
    top of our DNA, a code that -- unlike DNA -- can
    change during our lifetimes.

Many studies involve twins
59
  • In the past 5 years, epigenetics researchers
    have theorized that
  • 1. our diet,
  • 2. the chemicals we are exposed to and even
  • 3. our behavior toward one another
  • can cause changes in the way our genes are
    expressed, and contribute (by making people more
    susceptible to) or trigger mental illnesses like
    schizophrenia and bipolar disorder - and some of
    the epigenetic changes may even be passed on to
    future generations.

60
Mitochondrial DNA
  • Extranuclear DNA is found as small circles in
    mitochondria and chloroplasts
  • This DNA is reproduced and transmitted to
    daughter cells
  • These cytoplasmic genes do not display Mendelian
    inheritance (no meiosis)
  • Mutations in mitochondrial DNA (passed on by the
    mother only) can cause rare human diseases.

61
The Y Chromosome
62
The Evolution of the Y Chromosome
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