The Chromosomal Basis of Inheritance

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Chapter 15

• The Chromosomal Basis of Inheritance

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Early Days of Genetics

• Pre 1900, geneticists and cytologists studied
  mitosis and meiosis.
• In 1900, scientists in the two fields began to
  see parallels between the behavior of chromosomes
  and Mendels heredity factors during the sexual
  life cycle.

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Early Days of Genetics

• Walter Sutton and Theodore Boveri and others
  working independently began to recognize the
  parallels.
• The things they noticed were
• Chromosomes and genes are present in pairs in
  diploid cells.
• Homologous chromosomes separate and alleles
  segregate during the process of meiosis.
• Fertilization restores the paired conditions for
  both chromosomes and genes.
• The chromosomal theory of inheritance began to
  take shape.

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The Chromosomal Theory of Inheritance

• This theory suggested that
• Mendelian genes have specific loci on
  chromosomes.
• Chromosomes undergo segregation and independent
  assortment.

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Thomas Hunt Morgan

• Initially, Morgan was skeptical about the
  chromosomal theory of inheritance and Mendelism.
  However, his results proved otherwise.
• Around 1906, Morgan began to piece together the
  first solid evidence associating specific genes
  with specific chromosomes.

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Morgans Organism of Study

• Morgan chose the fruit fly (Drosophila
  melanogaster) for its ease of use, heartiness,
  and prolific breeding habits.

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Drosophila melanogaster

• Another thing making the fruit flies an ideal
  tool for study is that they only have 4
  chromosomes (3 pairs of autosomes and 1 pair of
  sex chromosomes--Females XX Males XY).
• One drawback there were no suppliers of fruit
  flies so he had to capture and breed his own.

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White Eyed Mutants

• After about a year of breeding and studying,
  Morgan found a white eyed fly (normal eye color
  is red).
• This eye color was due to a mutation and is known
  as the mutant phenotype.
• Morgan and his students invented a notation that
  is still used today to denote a mutant--a
  lowercase letter, w.
• Writing the lowercase letter with a , (w)
  superscript denotes the wild type phenotype.

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Experiments With the Mutant

• Morgan immediately mated the white eyed male with
  a red eyed female and found all of the F1
  offspring have red eyes--suggesting that red is
  the dominant allele.

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Experiments With the Mutant

• He also found that when mating the F1 generation,
  the F2 exhibited the 31 ratio of red eyes to
  white eyes, but only males had white eyes, and
  they were present in a 50/50 ratio of red to
  white.

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Morgans Conclusion

• Somehow the eye color of the fly is linked to its
  sex. (If not, 1/2 of the white eyed offspring
  would have been male, the other half would have
  been female).
• Since females are XX and males are XY, he
  concluded that the gene for eye color must be
  located on the X chromosome, with no
  corresponding gene on the Y chromosome.

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Morgans Reasoning and Analysis

• In a male fly, having a single copy of the mutant
  allele would give the mutant trait, white eyes.
  Since females have 2 X chromosomes and all of the
  F1 males have red eyes, there is no way for the
  females to have white eyes in this generation.

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In Support of Sex Linkage

• This finding lent support to the chromosomal
  theory of inheritance--a specific gene is carried
  on a specific chromosome.
• It also provided data regarding sex linkage.
  That is, genes located on the sex chromosomes
  exhibit unique inheritance patterns and unique
  ratios in the offspring.

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Sex-Linkage Continued

• Now that you know a little about sex linkage,
  most sex-linked genes are only found on the X
  chromosome.
• Females can pass such a disorder (gene) on to
  both male and female offspring.
• Males can only pass a disorder (gene) on to
  daughters only.

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Sex-Linkage Continued

• Sex linked recessives are only displayed in
  females when they are inherited in the homozygous
  condition.
• Males display the trait when they inherit one
  copy of the gene (said to be hemizygous).
• Color blind example.

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Linkage

• Some genes are said to be sex linked.
• Others are simply said to be linked. They are on
  autosomes.
• They are inherited together with other genes and
  the results of breeding experiments lead to
  results different from those predicted by
  Mendels law of independent assortment.

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Morgans Evidence of Linkage

• Morgan used more mutant traits that he
  discovered.
• Normal fruit flies have gray bodies and normal
  wings.
• 2 mutants he noticed had black (b) bodies and
  vestigial wings (vg).
• It was known that these mutations are autosomal
  and recessive.
• He didnt know if the traits were on the same or
  different chromosomes, however.

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To Determine Where the Alleles for these Traits
Were

• Morgan crossed flies until he got true-breeding
  wild-type flies and true-breeding double mutant
  flies for black bodies and vestigial wings.
• He could now perform a series of crosses to see
  if the alleles for these traits were on the same
  chromosomes or were on different ones.

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His First Cross

• He crossed the homozygous wild-type fly with the
  double mutant (homozygous recessive) and got a
  heterozygote.
• Remember, both true breeding flies produce only
  one type of gamete, so a heterozygote in the F1
  is assured.

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Are they on the Same Chromosome?

• Next, he performed a cross of the hybrid F1
  offspring with another double mutant.
• If the genes were on different chromosomes, then
  4 different types of offspring would be seen in a
  1111 ratio.

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If they are on the Same Chromosome

• If they are on the same chromosome and no
  crossing over occurs, then we should see a 11
  ratio of the parental phenotypes.

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If they are on the Same Chromosome

• and you see some crossing over and the genes are
  very close together, most of the offspring will
  look like the parents but some will be
  recombinants.
• This is exactly what Morgan saw!

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Crossing Over

• The whole idea of crossing over came from these
  experiments that Morgan performed. From the
  results, he reasoned that since the numbers
  didnt fit what was supposed to be happening,
  something else must be occurring.
• He reasoned that somehow a physical breakage must
  be occurring between the homologous chromosomes,
  something we now call crossing over.

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Additional Things to Come From These Experiments

• The idea of a linkage map using the recombination
  frequencies of genes.
• Determination of the order of genes.
• Gene mapping to determine where the genes were
  located.

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Crossing Over and Gene Mixing

• Crossing Over

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Sex Determination

• Whether or not a person is male or female is
  determined from their genotype XX is female XY
  is male.
• In humans, the father determines the sex of the
  baby.
• The chance of being a male or female is 50/50.
  Half of the sperm will inherit a Y, the other
  half will inherit the X.

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Sex Determination and the Y Chromosome

• The Y chromosome contains a region (SRY gene)
  which codes for proteins that induce the gonads
  to form testes.
• In the absence of this protein, the gonads form
  ovaries.

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Sex Determination and the X Chromosome

• Inheriting an X chromosome from dad will give a
  female 2 X chromosomes.
• Only one functions within the cell, the other is
  inactivated.
• It becomes a Barr body.
• The Barr body becomes reactivated in gametes so
  all of them have an active X chromosome when
  produced.

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X Inactivation

• This process is a totally random event and occurs
  independently in embryonic cells at the time of X
  inactivation.
• Females consist of a mosaic of active X
  genes--those derived from the father and those
  derived from the mother.

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X Inactivation

• As the embryo continues to divide mitotically,
  the we now have groups of cells with active X
  chromosomes derived from the mom, and active X
  chromosomes derived from dad.
• If a female is heterozygous for a sex linked
  trait, approximately 1/2 of the cells will
  express one gene, and 1/2 will express the other
  gene.

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X Inactivation and Mosaicism

• X inactivation can be seen in calico cats.
• It can also be seen in a sweat gland disorder.

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Nondisjunction

• Normally, in meiosis, the chromosomes are
  distributed without fail and the numbers of
  chromosomes remains the same throughout the
  generations.
• Occasionally, chromosomes dont get separated
  properly in meiosis I or II.
• Some gametes fail to receive a copy of a
  chromosome others receive 2 copies.

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Aneuploidy

• When nondisjunction occurs and is followed by
  fertilization, a situation arises where an
  abnormal number of chromosomes are present in the
  developing organism.

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Aneuploidy

• A cell with triple the number of a chromosome is
  known as trisomy.
• Trisomy 21 or Down Syndrome is an example.
• Having only one copy of the cell produces a
  situation known as monosomy.

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Nondisjunction and Mitosis

• Nondisjunction occurs in mitosis too.
• If it occurs very early on, then the organism, if
  it survives, will likely have a large number of
  phenotypic abnormalities.

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Chromosomal Alterations

• 1. Deletion--a gene or base pair is lost.
• 2. Duplication--a segment of DNA gets repeated.
• 3. Inversion--occurs when a chromosomal fragment
  flip-flops and reattaches to the original
  chromosome.
• 4. Translocation--occurs when a fragment from one
  chromosome is lost and becomes attached to
  another chromosome.

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Deletions and Duplications

• Occur most often during meiosis because of
  crossing over.

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Duplications and Translocations

• These dont alter the balance of genes, but the
  order on the chromosome is disrupted.
• This effects the neighboring genes and the
  expression of the duplicated/translocated genes.
• They are usually lethal.

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Non-Lethal Disruptions

• Aneuploidy--Down Syndrome. It isnt a
  duplication event, but essentially is like a
  duplication event.

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Aneuploidy

• Klienfelter Syndrome-XXY males. Have male sex
  organs but their testes are small and they are
  sterile.
• Also have other feminine characteristics such as
  large breasts.
• They can be of normal intelligence, but some
  often exhibit some metal impairments.

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Aneuploidy

• XXX females cannot be distinguished from any
  other female except by karyotype.
• XO are females with Turners syndrome. It is the
  only known monosomy in humans. They are sterile
  because their sex organs dont mature, can
  develop 2 sex characteristics with hormone
  treatment.

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Extranuclear Genes

• These are the genes found on the chromosomes of
  organelles such as mitochondria and chloroplasts.
• These are derived from the mother and replicate
  themselves.
• They code for the proteins and RNA that they use
  to perform their particular functions.