The Chromosomal Basis of Inheritance

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The Chromosomal Basis of Inheritance

• Chapter 15

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New knowledge confirms Mendels principles

• 1890 Cell biologists understand process of
  meiosis.
• 1902 Confirmed that chromosomes are paired in
  diploid cells, and that they separate in meiosis.
• Biologists develop the chromosome theory of
  inheritance
• Mendels factors, now genes are located
  on chromosomes.
• Chromosomes segregate and independently
  assort during gamete formation.
• Important work started in 1910 by Thomas Hunt
  Morgan from Columbia University who performed
  experiments with the fruit fly Drosophila
  melanogaster These flies
• Are easily cultured in the laboratory (live in
  small jars can be anesthetized).
• Are prolific breeders (100s of eggs laid).
• Have a short generation time (10 days).
• Have only four pairs of chromosomes which are
  easily seen with a microscope.

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An exception to Mendels rule

• Linked genes -- Genes located on the same
  chromosome, which do not indepedently assort and
  tend to be inherited together.
• B normal body color b black body
• W normal wing shape w vestigial wing
• BbWw x bbww ? 1 norm/norm 1 norm/vest 1
  black/norm 1 black/vest (expected)
• BbWw x bbww ? 5 norm/norm 1 norm/vest 1
  black/norm 5 black/vest
  (observed)
• Sturtevant hypothesized that probability of
  crossing over between two genes is directly
  proportional to the distance between them.
• He used recombination frequencies between genes
  to assign them a linear position on a chromosome
  map.
• One map unit 1 recombination frequency genes
  farthest apart have highest recombination
  frequency.

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Discovery of a Sex-Linked Gene

• Sex-linked genes -- Genes located on sex
  chromosomes, commonly applied only to genes on
  the X chromosome.
• Morgan discovered a male fly with white eyes
  instead of the wild-type red eyes. Morgan mated
  this mutant white-eyed male with a red-eyed
  female.
• w white-eye allele
• w red-eye or wild-type allele
• P generation Xw Xw x Xw Y
• F1 generation Xw Xw and Xw Y (all
  red-eyed)
• F2 generation Xw Xw and Xw Xw (all
  females red-eyed)
• Xw Y and Xw Y
  (half males red half males white)
• Morgans conclusions
• If eye color is located only on the X chromosome,
  then females (XX) carry two copies of the gene,
  while males (XY) have only one.
• Since the mutant allele is recessive, a
  white-eyed female must have that allele on both X
  chromosomes (impossible in this case).
• A white-eyed male has no wild-type allele to mask
  the recessive mutant allele, so a single copy
  results in white eyes.

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Sex-Linked Disorders in Humans

• Color blindness, Duchenne muscular dystrophy,
  hemophilia.
• Human X-chromosome is much larger than the Y
  more genes on the X, many without a homologous
  loci on the Y.
• Fathers pass X-linked alleles to only and all of
  their daughters.
• Males receive their X chromosome only from their
  mothers.
• Fathers cannot pass X-linked traits to their
  sons.
• Mothers can pass X-linked alleles to both sons
  and daughters.
• A female that is heterozygous for the trait can
  be a carrier, but not show the recessive trait
  herself far more males than females have
  sex-linked disorders.
• Males are said to be hemizygous (having only one
  copy of a gene in a diploid organism).

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Sex-Limited/Sex-Influenced Traits

• Autosomal traits which affect one gender more
  than the other.
• A dominant gene causes a rare type of uterine
  cancer, but only affects women.
• A form of baldness also caused by a dominant gene
  usually only affects men because of hormone
  levels.

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X Inactivation in Females

• In female mammals, most diploid cells have only
  one fully functional X chromosome one of the 2
  chromosomes is inactivated during embryonic
  development.
• Inactive X chromosome condenses into an object
  called a Barr body most Barr body genes are not
  expressed.
• Barr bodies are highly methylated compared to
  active DNA Methyl groups (-CH3) attach to
  cytosine.
• Female mammals are a mosaic of two types of
  cells, one with an active X from the father and
  one with an active X from the mother
  inactivation appears to happen randomly.
• Examples of this type of mosaicism are coloration
  in calico cats.

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Humans Fragile X, muscular dystrophies, patchy
skin discoloration
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Genetic Disorders Alterations of Chromosome
Number

• Aneuploidy -- having an abnormal number of
  certain chromosomes.
• Three copies of a chromosome is called trisomy
  (Downs Syndrome, or Trisomy 21) missing a
  chromosome is called monosomy (Turners
  Syndrome).
• Polyploidy -- more than two complete chromosome
  sets.
• Triploidy means three haploid chromosome sets
  (3N) may be produced by fertilization of an
  abnormal diploid egg.
• Tetraploidy means four haploid chromosome sets
  (4N) may result by mitosis without cytokinesis.
• Polyploidy is common in plants, but occurs rarely
  in animals.
• Nondisjunction -- error in meiosis when
  homologous chromosomes or sister chromatids fail
  to separate into different gametes.

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Genetic Disorders Alterations of Chromosome
Number(cont)

• Aneuploidy usually prevents normal embryonic
  development and often results in spontaneous
  abortion.
• Some types cause less severe problems.
• Down syndrome (1 in 700 live births in U.S.)
  characteristic facial features, short stature,
  heart defects, mental retardation.
• Correlates with maternal age time lag prior to
  completion of meiosis at ovulation?
• Rarer disorders are Patau syndrome (trisomy 13)
  and Edwards syndrome (trisomy 18) incompatable
  with life.
• Sex chromosome aneuploidy
• Klinefelter Syndrome (usually XXY) sterile males
  with feminine body characteristics.
• Extra Y (or super-male , XYY) taller males
  with higher testosterone production.
• Turner Syndrome (XO) only known viable human
  monosomy short stature sexual characteristics
  fail to develop sterile.

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Genetic Disorders Alterations of Chromosome
Structure

• Chromosome breakage can alter chromosome
  structure in four ways
• 1. Deletion loss of a fragment of chromosome.
• 2. Duplication lost fragment attaches to a
  homologous chromosome, repeating a sequence.
• 3. Translocation lost fragment joins to a
  nonhomologous chromosome.
• 4. Inversion lost fragment reattaches to the
  original chromosome in reverse.
• These errors usually happen during crossing-over.

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Genetic Disorders Alterations of Chromosome
Structure(cont)

• Cri du chat syndrome deletion on chromosome
  mental retardation, unusual facial features, and
  cats cry.
• Chronic myelogenous leukemia (CML) portion of
  chromosome 22 switches places with fragment from
  chromosome 9.
• Some cases of Down syndrome the third chromosome
  21 translocates to chromosome 15.
• Prader-Willi syndrome deletion from the paternal
  chromosome 15 mental retardation, obesity, short
  stature.
• Angelman syndrome same deletion from the
  maternal chromosome 15 uncontrollable
  spontaneous laughter, jerky movements, and other
  mental symptoms.
• Genomic imprinting -- changes in chromosomes
  inherited from males and females certain genes
  expressed differently depending upon whether
  inherited from the ovum or from the sperm cell.

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Genetic Disorders Alterations of Chromosome
Structure(cont)

• Fragile X syndrome (1 in 1500 males 1 in 2500
  females) most common genetic cause of mental
  retardation.
• Caused by triplet repeat (CGG) repeated up to 50
  times on the tip of a normal X chromosome
  repeated more than 200 times in a fragile X
  chromosome.
• Syndrome more likely to appear if the abnormal X
  chromosome is inherited from the mother
  chromosomes in ova are more likely to acquire new
  CGG triplets than chromosomes in sperm.
• Maternal imprinting explains why fragile-X
  disorder is more common in males. Males (XY)
  inherit the fragile X chromosome only from their
  mothers.
• Heterozygous carrier females are usually only
  mildly retarded.

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