Chromosome Variation
5' end
3' end
3' end
5' end
Chromatin into chromosomes
Structure
(a) DNA wraps around the
histone proteins to form
chromatin, the material that
makes up the chromosomes
(b) Eukaryotic chromosome
Telomeres
• Natural ends of a
chromosome
• Stabilizes the
chromosome so that it
does not degrade
– At the end of each
telomere are many short
telomeric sequences.
– Longer, more complex
telomere-associated
sequences are found
adjacent to the telomeric
sequences.
A human karyotype
Types of Mutations
• Chromosome rearrangements
– alter the structure of chromosomes
• Aneuploidy
– one or more individual chromosomes are
added or deleted
• Polyploidy
– one or more complete sets of chromosomes
are added
Chromosome Rearrangements
1) Duplication
• Part of
chromosome is
doubled
– Tandem (figure)
– Displaced: ABCDEFGEF
– Reverse: ABCDEFFEG
• Gene dosage
problems may arise
1) Duplication
• The human genome consists of numerous
duplicated sequences called segmental
duplications which are more than 1000 base
pairs in length
• Examining the DNA sequences ireveals that
about 4% of the human genome is composed of
segmental duplications
2) Deletion
• Easily
detected
because the
chromosome
is shortened
• Many
deletions are
lethal in the
homozygous
state
3) Inversion
• Pericentric - includes the centromere
3) Inversion
• Paracentric does not
include the
centromere
Crossing over within a pericentric inversion
leads to abnormal gametes in a
heterozygous individual
4) Translocation
• Nonreciprocal - genetic material moves
from one chromosome to another without
any reciprocal exchange
• Reciprocal - there is an exchange of
segments between two chromosomes
4) Translocation
• Robertsonian
Individual heterozygous for a reciprocal translation, crosslike structures form
during homologous pairing
Fragile Sites
• constrictions or gaps at particular locations of a
chromosome, so-called because they are prone
to breakage
• Common - present in all humans; location of
chromosome breakage and rearragement in
cancer cells
• Rare - inherited as a Mendelian trait; associated
with genetic disorders
Fragile Sites
• Fragile X syndrome
– increase in the number of
repeats of a CGG
trinucleotide
– Associated with mental
retardation
– 1 in 1250 male births
– Most prominent symptoms
include an elongated face,
large or protruding ears,
and low muscle tone.
Aneuploidy
• Nullisomy - loss of both members of
homologues (2n-2)
• Monosomy - loss of 1 chromosome (2n-1)
• Trisomy - addition of 1 chromosome
(2n+1)
• Tetrasomy - gain of 2 homologues (2n+2)
• Sex-chromosome aneuploids - e.g.
Kilnefelter's and Turner's syndromes
• Autosomal - e.g. Down's syndrome
Individuals with translocations are at
increased risk of producing children with
Down's syndrome
Aneuploidy
• Trisomy 18 (Edward syndrome)
- 1 in 8000 births; babies are
severely retarded and have lowset ears, a short neck, deformed
feet, clenched fingers, heart
problems, and other disabilities.
Few live for more than a year
after birth
• Trisomy 13 (Patau syndrome) 1 in 15000; severe mental
retardation, a small head, sloping
forehead, small eyes, cleft lip and
palate, extra fingers and toes,
and numerous other problems.
About half of children with trisomy
13 die within the first month of life
Aneuploidy
• Trisomy 8 (Warkany
Syndrome 1) - 1 in
25000 to 1 in 50000;
mental retardation,
contracted fingers
and toes, low-set
malformed ears, and
a prominent forehead.
Many who have this
condition have normal
life expectancy
Mosaicism
• Mosaicism - A condition in which an individual
is composed of a mixture of cells that are
karyotypically or genotypically distinct
• Nondisjunction in a mitotic division may
generate patches of cells in which every cell has
a chromosome abnormality and other patches in
which every cell has a normal karyotype.
• This type of nondisjunction leads to regions of
tissue with different chromosome
constitutions
Polyploidy
• Common in plants, especially in
agricultural crops
– Major mechanism by which plants have
evolved
• Also in invertebrates, fishes, and some
amphibians and reptiles
Polyploidy
• Autopolyploidy - all chromosome sets are
from a single species
• Allopolyploidy - chromosome sets are from
two or more species
Allopolyploidy arises
from hybridization
between two
chromosomes followed
by chromosome doubling
Significance
• Cell volume is correlated with nuclear volume,
which, in turn, is determined by genome size.
• Thus, the increase in chromosome number in
polyploidy is often associated with an increase in
cell size, and many polyploids are physically
larger than diploids
– larger fruits, flowers, etc.
– Ex. Allopolyploid bananas (3n) are sterile and
produce no seeds; thus they are sold commercially
Significance
• Since allopolyploidy requires hybridization, this
happens less frequently in animals
– Behavior prevents interbreeding
• Only a few human polyploid babies have been
reported, and most died within a few days of
birth. Polyploidy—usually triploidy—is seen in
about 10% of all spontaneously aborted human
fetuses.
• Gene evolution
– duplication can free a set of genes for
change, while the original copy provides
original function
– Inversions can suppress recombination
– Polyploidy often gives rise to new species
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