beyond Mendel - the chromosomal basis of inheritance

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beyond Mendel - the chromosomal basis of
inheritance

• biology 1

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• Mendels Laws based on chromosomal behavior
• Specific advances in the knowledge of genetics
• Sex-linkage
• Recombination
• Linked genes
• Sex-linked disorders
• Alterations of chromosome number/structure

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A chromosome basis for Mendel

• Observed by late 1900s
• 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
• This led to the chromosome theory of inheritance
• Mendelian factors or genes are located in
  chromosomes
• It is the chromosomes that segregate and
  independently assort

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• Thomas Morgan substantiated this theory with work
  on fruit flies, Drosophila (2n 8)
• Adopted a new method of symbolizing genes and
  alleles
• A genes symbol is based on the first mutant,
  non-wild type discovered (e.g. w white eye
  allele in Drosophila)
• If the mutant is dominant, the first letter is
  capitalized (e.g. Cy curly wings in Drosophila)
• Wild type (normal) gets superscript (e.g. Cy
  is the allele for normal, straight wings)

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Sex-linkage

• Morgan crossed a white-eyed male (w) with a
  red-eyed female (ww)
• In the F1, all progeny had red eyes, implying
  that red-eye was dominant
• In the F2, white-eye trait was only found in
  males - females were always red-eye
• Deduction the gene for eye color is on the X
  chromosome, since
• If eye color is located only on the x-chromosome,
  then females carry to copies of the gene (XX),
  while males (XY) only carry one
• Since the mutant allele is recessive, wa white
  eyed female must have that allele on both X
  chromosomes, which would be impossible for F2
  females
• A white-eyed male has no wild type to mask the
  recessive mutant allele, so a single copy of the
  mutant allele confers white eyes

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Linked genes

• Linked genes are located in the same chromosome
  and tend to be inherited together (ie, do not
  sort independently, 9331 ratio is not
  preserved)
• For example, in a non-linked dihybrid test-cross,
  e.g.
• YyRr x yyrr
• Yellow round Green wrinkled
• F1 YyRr yyrr yyRr Yyrr
• Yellow round green wrinkled green round
  yellow wrinkled
• 1 1 1
  1
• (Parental types) (Recombinant types)

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• If genes are totally linked, some possible
  phenotypes should not appear (although sometimes
  they can, if linakge is not complete)
• For example, Morgan crossed black body (b),
  normal wings (vg) vs. wild type body (b),
  vestigial wings (vg)
• Conclusion the two genes are neither completely
  linked or unlinked

Recombination frequency 391 recomb./2300
offspring 17
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• If genes are completely linked, then expect only
  parental types in offspring
• Crossing over in Prophase I accounts for
  recombination of linked genes
• Genes that are located in the same chromosome
  close to each other are less likely to separate
  during synapsis. Genes that are further apart are
  more likely to be separated
• If crossing-over occurs randomly, percentage of
  crossing-over can be used to map location of
  genes on a chromosome
• When linked genes are further apart than 50 cM,
  they are indistinguishable to non-linked genes
• Cytological mapping can now pinpoint precise
  location on chromosome

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Sex-linked disorders

• Since the x-chromosome is larger, there are more
  x-linked traits most have no homologous loci on
  the y-chromosome
• Most genes on the y-chromosome have no
  x-counterparts, and encode traits only found in
  males
• Examples of sex-linked traits include color
  blindness and hemophilia.
• Fathers pass X-linked alleles to only, and all of
  their daughters. Fathers cannot pass x-sex-linked
  traits to sons
• Mothers can pass X-linked alleles to both sons
  and daughters
• X-sex-linked traits are rarer in females since
  they tend to be recessive, and thus require a
  homozygous condition
• Any male that receives an X-sex-linked
  chromosome, recessive or not, will express it,
  since they are hemizygous
• As a consequence, males tend to display more
  sex-linked disorders.

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X-inactivation

• To prevent females from receiving a double-dose
  of sex-linked traits, one X-chromosome is
  typically inactivated, contracting into a dense
  object called a barr body
• Barr bodies are reactivated in gonadal cells for
  meiosis
• Choice of which X to inactivate (maternal or
  paternal inherited) is randomly selected in
  embryonic cells
• Thus heterozygous females display sex-linked
  traits on a 50/50 basis (e.g., calico cats)
• Formation of barr body appears to be by
  methylation of cytosine

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Alteration of chromosome number

• Meiotic nondisjunction a homologous pair does
  not separate in Metaphase I, or chromatids do not
  separate in Metaphase II
• Mitotic nondisjunction occurs at metaphase. If
  early in embryonic development, can be passed
  onto a large number of cells
• Aneuploidy - an abnormal number of chromosomes
  (trisomic or monosomic) for example, Down
  syndrome is trisomy of chromosome 21
• Polyploidy - a chromosome number that is more
  than two complete chromosome sets this is very
  common in plants

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Alteration of chromosome structure

• Fragments breaking off from chromosomes may
  result in deletions
• Addition of those fragments to
• Homologous chromosomes causes a replication
• Nonhomologous chromosomes causes a translocation
• Original chromosome in reverse order causes an
  inversion
• Crossovers are usually reciprocal, but sometimes
  a chromatid gives up more genes than it receives
  in an unequal crossover (creates one deletion and
  one duplication)

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Human disorders resulting from chromosomal
alteration

• Down syndrome effects 1/700. The result of
  trisomy on chromosome 21 (an autosome), causes
  specific facial features, heart defects,
  retardation, and proneness to leukemia
• Sex chromosome aneuploidies are typically less
  severe because
• The Y chromosome carries less genes
• Copies of the X-chromosome may be inactivated as
  barr bodies