The Human Chromosome

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The Human Chromosome
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What Is Karyotyping?

• A typical karyotype is a preparation of an
  individuals metaphase chromosomes, sorted out by
  length, shape, centromere location, and other
  defining features.
• Large abnormalities in chromosome structure or an
  altered chromosome number can be pinpointed by
  comparing an individuals karyotype against a
  standard karyotype for the species.

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Making A Karyotype

• Human chromosomes are in their most condensed
  form and easiest to identify when a cell is at
  metaphase in mitosis.
• Using blood cells (typically) scientists induce
  metaphase, place the cells in a hypotonic
  solution (causing them to swell). The chromosomes
  move away from each other and then the cells are
  placed on a slide.
• The cells are then photographed, and the
  photograph is cut with scissors or with a
  computers cut-n-paste tool.
• The chromosomes are then lined up by size and
  shape.

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Spectral Karyotypes

• A more recent diagnostic tool, uses a range of
  fluorescent dyes that bind to specific parts of
  chromosomes.
• Analysis of the resulting rainbow-hued karyotype
  often reveals abnormalities that would not
  otherwise be discernable.

This chromosome (9) exchanged a segment of itself
with the non-homologous chromosome 22. The end of
chromosome 9 affects mitotic cell division and 22
affects expression of another gene. This mutation
results in chronic myelogenous leukemia (CML) in
which the body produces far too many white blood
cells, which give rise to malignant cells in bone
tissues.
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Autosomal Inheritance Patterns

• Your body contains two types of chromosomes sex
  chromosomes and autosomal chromosomes.
• Sex chromosomes determine whether you are male or
  female.
• Autosomes determine every other trait in your
  body from the color of your eyes, to how fast
  your metabolism is.
• Most human traits arise from complex gene
  interactions, but many can be traced to autosomal
  dominant or autosomal recessive alleles that are
  inherited in simple patterns.
• Some of these alleles cause genetic disorders.

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Autosomal Dominant Inheritance

• To inherit an autosomal dominant mutation, you
  only need to inherit a single mutated or altered
  allele from either your mother or your father to
  show the trait.
• Polydactyly
• This mutation causes an individual to grow more
  than 5 fingers or toes.
• Only one parent needs to pass this onto their
  child for the child to have it.

One dominant allele (red) is fully expressed in
carriers. Polydactyly, the inheritance of more
than five fingers or toes, is an autosomal
disorder.
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Autosomal Recessive Inheritance
Both parents are heterozygous carriers of the
recessive allele (red), and a child must inherit
both recessive alleles to show the trait.

• To inherit an autosomal recessive mutation, you
  need to inherit mutated or altered alleles from
  BOTH your mother and your father to show the
  trait.
• Albinism
• is characterized by the complete or partial
  absence of pigment in the skin, hair and eyes due
  to absence or defect of an enzyme involved in the
  production of melanin.

Tanzania has one of the highest incidences of
albanism in the world! Over 150,000 albinos live
there.
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Sex Determinism

• The Y chromosome carries 255 genes, one of which
  is the SRY gene that gives rise to the formation
  of testes.
• The X chromosome carries 1,141 genes (no SRY
  gene).
• It includes genes that affect the distribution of
  body hair and fat (which is why if your mothers
  father isnt bald, you wont be either!)
• Most of its genes deal with non-sexual traits
  like blood-clotting.

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X-Linked Inheritance

• Sometimes, genetic disorders are carried on the
  X-chromosome.
• Recessive alleles on the X-chromosome affect more
  males than females as the female has a second X
  that will mask the recessive Xs effects.
• Males are not protected, because they only
  inherit one X chromosome.
• An affected father cannot pass on the recessive
  allele to his son (because hell only pass on the
  Y-chromosome) but he WILL pass it onto his
  daughters.
• EXAMPLES
• Hemophilia A
• Red-Green Color Blindness
• Duchenne Muscular Dystophy

Can you see the number? 12-20 of white males
cannot! They have inherited red-green color
blindness from their mothers, and have the
inability to distinguish some or all shades of
red and green.
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Aneuploidy

• In aneuploidy, cells usually have one extra or
  one less chromosome.
• Autosomal aneuploidy is usually fatal and linked
  to most miscarriages.
• Aneuploidy typically arises through
  nondisjunction.
• Nondisjunction is where one or more pairs of
  chromosomes do not separate as they should during
  meiosis or mitosis.
• Polyloidy is where cells have three or more of
  each type of chromosome.
• Examples of Aneuploidy
• Downs Syndrome
• Turners Syndrome
• Kleinfelter Syndrome
• XXX syndrome
• XYY condition

Downs syndrome is caused by the presence of all
or part of an extra 21 chromosome, known as
trisomy 21. Downs syndrome is associated with
some impairment of cognitive ability and physical
growth.
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Female Sex Chromosome Abnomalities

• Sometimes females will inherit different amounts
  of X-chromosomes. (This is called aneuploidy or
  non-disjunction)
• Turners Syndrome
• A female inherits one X chromosome and no
  corresponding X or Y chromosome.
• 98 of embryos spontaneously abort.
• Results in several developmental abnormalities.

One characteristic sign of Turners Syndrome is
the presence of neck webbing and extra skin.
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Male Sex Chromosome Abnormalities

• Kleinfelter Syndrome
• 1 in 500 males inherit XXY chromosomes.
• Results in normal range of intelligence, though
  may also have some learning disabilities.
• Have several developmental side effects.
• XYY condition
• 1 in 500 to 1,000 males inherit XYY.
• Mild mental impariment.

A karyotype may be performed to determine the
presence of either Kleinfelter or XYY condition.
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Main Categories

• One or more changes in the physical structure of
  a chromosome may give rise to a genetic disorder
  or abnormality.
• Such changes are rare, but they do occur
  spontaneously in nature.
• Some can also be induced due to exposure to
  certain chemicals or irradiation.

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Duplication
Normal chromosome

• Even normal chromosomes have DNA sequences that
  are repeated two or more times.
• Duplication can occur through unequal crossovers
  at prophase I.
• Some duplications cause neural problems and
  physical abnormalities.
• Example Huntingtons Disease

One segment repeated.
Three repeats
Huntingtons Disease causes progressive
neurological degeneration. Symptoms typically do
not appear until after age 30. It is cased by a
repeating CAG sequence that disrupts normal brain
cell development.
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Deletion

• A deletion is a loss of some portion of a
  chromosome, as by unequal crossovers, inversions,
  or chemical attacks.
• Most deletions cause serious disorders or death.
• Missing or broken genes disrupt the bodys
  growth, development, and metabolism.
• Example Cri-Du-Chat Syndrome

Segment C deleted
A tiny deletion from human chromosome 5 results
in an abnormally shaped larynx and mental
impairment. Crying infants sound like cats
meowing. Hence, Cri-Du-Chat (cat-cry in French).
Above is a picture of a male infant diagnose with
Cri-Du-Chat, and the same boy 4 years later.
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Inversion

• With an inversion, part of the sequence of DNA
  within the chromosome becomes oriented in the
  reverse direction, with no molecular loss.
• This can cause problems in meiosis.
• Chromosomes can mispair, and deletions may occur
  that can reduce viability of gametes.
• Some individuals (carriers) do not even know that
  they have an inverted chromosome region until a
  genetic disorder or abnormality surfaces in one
  or more children.

segments G, H, I become inverted
Inversions and deletions often occur together, a
result of unequal recombination events.
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Translocation
chromosome

• With translocation, a broken part of one
  chromosome becomes attached to another
  chromosome.
• Most translocations are reciprocal, in that both
  of the two chromosomes exchange broken parts.
• Translocations often cause reduced fertility,
  because affected chromosomes have difficulty
  segregating in meiosis.
• Example
• Some sarcomas
• Lymphoma
• Myeloma
• Leukemia

nonhomologous chromosome
reciprocal translocation