Matthew 18:11

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• Matthew 1811
• 11 For the Son of man is come to save that which
  was lost.

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Chromosomal Basis of Inheritance

• Timothy G. Standish, Ph. D.

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Introduction- Gregor Mendel

• Father of classical genetics.
• Born 1822 to peasant family in the Czech village
  of Heinzendorf part of the Austro-Hungarian
  empire at the time.
• Austrian Augustinian monk (Actually from Brunn
  which is now in the Czech Republic).

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Gregor Mendel - Education

• Studied mathematics in Olmutz college.
• Attended University of Vienna 1851 - 1853.
  Influenced by
• Franz Unger, a plant physiologist who believed
  new species could come about via hybridization.
• Christian Doppler, physicist who discovered the
  Doppler effect. Sharpened his math skills.

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Gregor Mendel - Work

• Studied peas which he grew in a garden out side
  of the Abbey he lived in starting 1856 (3 years
  prior to publication of Origin of Species).
• Showed that the traits he studied behaved in a
  precise mathematical way and disproved the theory
  of "blended inheritance."

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Gregor Mendel - Work Cont.

• Published rules of transmission of genes in 1866
  (hand written in German, not Latin!). Work was
  totally ignored.
• Mendels work was rediscovered in 1900 by three
  botanists
• Carl Correns (Germany)
• Erich von Tschermak (Austria)
• Hugo de Vries (Holland)

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3 Reasons Mendels Work Was Ignored

• Mendel was not on the ball
• Biologists were idiots (at least when it came to
  math)
• Lack of independent supporting discoveries

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Reasons Mendels Work Was Ignored1) Mendel was
not on the ball

• Wrote in an obscure journal (Proceedings of the
  Natural History Society of Brunn).
• Wrote in German not Latin.
• Mendel was not well known and did not persevere
  in his attempt to push his ideas.

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Reasons Mendels Work Was Ignored2) Biologists
were idiots

• Biologists didnt understand math very well.
• Biologists were interested in the explaining the
  transmission of continuous traits like height,
  esp. after publication of Origin of Species in
  1859. Mendel suggested that inherited
  characteristics were discrete units
  (discontinuous).

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Reasons Mendels Work Was Ignored3) Lack of
independent supporting discoveries

• There was no Physical element in which Mendels
  inherited particles could be identified.
• By the turn of the century, chromosomes had been
  discovered (physical particles) and biologists
  were better at math.

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ChromosomesThe Physical Basis of Inheritance

• 1866 Mendel published his work
• 1875 Mitosis was first described
• 1890s Meiosis was described
• 1900 Mendel's work was rediscovered
• 1902 Walter Sutton, Theodore Boveri and others
  noted parallels between behavior of chromosomes
  and alleles.

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Chromosomal Theory of Inheritance

• Genes have specific loci on chromosomes.
• Chromosomes undergo segregation (meiosis) and
  independent assortment,
• Thus alleles of genes are independently assorted.

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Chromosomal Theory of Inheritance
Telophase II
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Independent Assortment
As long as genes are on different chromosomes,
they will assort independently
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Two Genes On One Chromosome
Telophase II
As long as genes on the same chromosome are
located a long distance apart, they will assort
independently due to crossing over during
prophase I of meiosis
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Thomas Hunt Morgan

• First to associate a trait (gene) with a
  chromosome.
• Worked with fruit flies (Drosophila melanogaster)
• Why fruit flies?
• Short generation time ( 2 weeks)
• Survives and breeds well in the lab
• Very large chromosomes in some cells
• Many aspects of phenotype are genetically
  controlled.

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Drosophila Nomenclature

• Wild type, phenotype in nature (i.e. red eyes
  and round wings)
• Mutants are alternatives to the wild type
• Fruit fly genes are named after the mutant
• Dominant mutations are capitalized (i.e. Hairless
  or H and Bar or B)
• Recessive mutants are named using lower case
  letters (i.e. black or b and white or w)

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Drosophila Mutations
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More Drosophila Mutations
Wild Type
ebony body ee
white eyes ww
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Sex Determination

• Two ways in which sex can be determined
• Environment
• Turtles - Temperature of development
• Some fish - Social structure
• Chromosomes - Three methods
• XO - Haploid/diploid ie bees, haploid males
  diploid females
• ZW - Heterogametic (ZW) females, homogametic (ZZ)
  males, ie birds
• XY - Heterogametic (XY) males, homogametic (XX)
  females, ie humans and Drosophila

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X Chromosome Human and Drosphila Genes Are Easy
To Find

• In humans and Drosophila, males are XY
• Thus males are haploid for the X chromosome
• Because of this, recessive genes on the X
  chromosome show up far more commonly in male than
  female phenotypes

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Morgans Discovery Of An X-Linked Drosophila Gene
A white-eyed male was discovered
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The Key To Morgans Discovery

• The key to Morgans discovery was the observation
  that all the white eyed individuals in the F2
  generation were males
• Without this vital data on the association of
  white eyes with being male, the gene for white
  eyes could have been seen as a simple recessive
  trait on an autosome
• This illustrates the importance of recording all
  the data possible and being alert to the
  possibility of interesting things being present
  in the data
• Fate favors the prepared mind (Louis Pasture)

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Human X-linked Recessive Genes

• Brown enamel - Tooth enamel appears brown rather
  than white
• Hemophilia - Two types
• A - Classic hemophilia, deficiency of blood
  clotting factor VIII
• B - Christmas disease, deficiency of blood
  clotting factor IX

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X-linked Recessive GenesRelated to sight

• Coloboma iridis - A fissure in the eyes iris
• Color Blindness - Two types
• Deutan - Decreased sensitivity to green light
• Protan - Decreased sensitivity to red light
• Congenital night blindness - Not due to a
  deficency of vitimin A
• Mocrophthalmia - Eyes fail to develop
• Optic atrophy - Degeneration of the optic nerves

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Variation In Chromosome Number - Polyploidy

• Polyploid individuals have more than two sets of
  chromosomes
• Many important commercial plants are polyploid
• Roses
• Navel oranges
• Seedless watermelons
• Polyploid individuals usually result from some
  sort of interruption during meiosis

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Variation In Chromosome Number - Aneuploidy

• Polyploid humans are unknown, but individuals
  with extra individual chromosomes are known.
• Having extra chromosomes or lacking some
  chromosomes is called aneuploidy
• Aneuploid individuals result from nondisjunction
  during meiosis

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Aneuploidy In Humans

• Most human aneuploids spontaneously abort
• The most viable variations in chromosome number
  are those that deal with the sex chromosomes
• XO - Turners Syndrome - Phenotypically females
• XXX- Super females
• XYY - Super Males - On average tend to be
  larger and less intelligent
• XXY - Klinefelters Syndrome - Phenotypically
  male
• Of the non-sex chromosome aneuploidys, Downs
  Syndrome, extra chromosome 21, tends to be the
  most viable
• Downs Syndrome is more common in children of
  mothers who gave birth after age 40

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Gene Dosage

• There seem to be elegant mechanisms for
  maintaining the correct dosage of genetic
  material in each cell
• When aneuploidy causes a change in the relative
  dose of one chromosome, problems result
• Another way in which dosage of genetic material
  can be changed is via macromutations

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Macromutations

• Four major types of Macromutations are
  recognized
• 1 Deletions - Loss of chromosome sections
• 2 Duplications - Duplication of chromosome
  sections
• 3 Inversions - Flipping of parts of chromosomes
• 4 Translocations - Movement of one part of a
  chromosome to another part

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Macromutation - Deletion
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Macromutation - Duplication
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Macromutation - Inversion
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Macromutation - Translocation
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The Lyon Hypothesis

• Having extra chromosomes causes problems (ie
  Downs Syndrome)
• Men have only one X chromosome and they are
  normal (at least they think so)
• Women have two X chromosomes and they are normal
• Mary Lyon proposed that the extra dosage of X
  chromosome that women have is compensated for by
  turning off one of the X chromosomes.
• This turned off chromosome can be observed as a
  Bar Body in metaphase female nuclei

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Consequences of X Chromosome Dosage Compensation

• During early development, X chromosomes are
  randomly turned off in female cells
• All daughter cells have the same X chromosome
  inactivated as their parental cell.
• Thus, females are a mosaic of patches of cells
  some patches expressing the genes on the paternal
  X chromosome, other patches expressing the
  maternal X chromome

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Consequences of X Chromosome Dosage Compensation
At some point (probably later than the 4 cell
stage) half the X chromosomes are turned off
Daughter cells inherit the mother cells
combination off and on X chromosomes
Because of dosage compensation, females are
thought to be a mosaic of patches of cells with
each patch expressing the same X chromosome, but
none expressing both chromosomes
Different patches of cells inherit different act
X chromosomes
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Why Calico Cats Are Usually Female

• Orange coat color is a sex-linked trait in cats
  (it is on the X chromosome)
• A female cat heterozygous for orange, has skin
  patches expressing the orange X with the other X
  chromosome turned off. In other patches the
  opposite occurs.

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Problem 1

• In Drosophila, vermilion (v) is recessive to red
  (v) eyes and miniature (m) wings are recessive
  to normal (m) wings. The following cross was
  made
• Male vvmm x vvmm Female
• What was the phenotype of the F1 generation?
• What F2 phenotypic ratio would you expect?
• If the actual F2 phenotypic numbers were
• 147 red eyed normal winged
• 49 vermilion eyed miniature winged,
• 2 red eyed miniature winged,
• 2 vermillion eyed normal winged,
• How would you explain this?

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Solution 1

• What was the phenotype of the F1 generation?
• vvmm makes vm gametes
• vvmm makes vm gametes
• Thus the F1 must be vvmm
• What F2 phenotypic ratio would you expect?
• 9 red eyed normal winged (v_m_)
• 3 red eyed miniature winged (v_mm)
• 3 vermilion eyed normal winged (vvm_)
• 1 vermilion eyed miniature winged (vvmm)

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Solution 1 Continued

• If the actual F2 phenotypic numbers were
• 147 red eyed normal winged
• 49 vermilion eyed miniature winged,
• 2 red eyed miniature winged,
• 2 vermilion eyed normal winged,
• How would you explain this?

F1 Gametes
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Solution 1 Continued
0.74 v_m_ (0.74200148)
0.01 v_mm (0.012002)
0.01 vvm_ (0.012002)
0.2401 vvmm
0.24 vvmm (0.2420048)
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Solution 1 Continued

• Vermillion and miniature winged are closely
  linked genes on the same chromosome
• The distance between vermilion and miniature is 1
  centimorgan
• The reason numbers in the cross do not fit the
  prediction of 1 centimorgan exactly is that the
  numbers are the result of chance and thus would
  not be expected to fit the predicted ratio
  perfectly

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Problem 2

• How is the gene tracked in the pedigree shown
  below inherited? In other words, what is its
  mode of inheritance?

Use deductive reasoning to solve this problem
Hypothesis 1 - Autosomal dominant
Hypothesis 2 - Autosomal recessive
Hypothesis 3 - Sex linked dominant
Hypothesis 4 - Sex linked recessive
Answer - Either sex linked recessive (most
likely) or autosomal recessive
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Problem 2

• How is the gene tracked in the pedigree shown
  below inherited? In other words, what is its
  mode of inheritance?

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Problem 3

• If two genes A and B are linked on the same
  chromosome and located 10 centimorgans apart, how
  many recombinant offspring would be expected in
  1,000 F2 offspring from the following cross
• AABB x aabb

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