Transcript Pierce chapter 9

Chapter 9 – Chromosomal
Variation
Chromosome Morphology
• Metacentric
– Centromere is centrally located; arms equal length
• “p” and “q” – “p” is smaller when there is a size difference
• Submetacentric
– Centromere is off center
• Acrocentric
– Centromere is close to one end
– p arm has satellites (knobs on stalks)
• Telocentric
– Centromere is at one end
– Not present in humans
Karyotype
• Complete set of
chromosomes arranged
in homologous pairs
• Sample is from an
actively dividing cell
– Chemical inhibits spindle
assembly formation
• Cell can not complete
mitosis
– Hypotonic solution swells
cell
• Allows chromosomes to
spread out
– Dropped on slide and
stained
Staining
• G banding
– Giemsa stain; most common
– Stains A-T rich regions
• C banding
– Stains centromeric heterochromatin and portions of
chromosomes with large sections of heterochromatin
• 1, 9, 16, Y
• R banding
– Stains G-C rich regions
– Gives opposite banding pattern of G banding
• Q banding
– UV light is used
– Same pattern as G banding
Staining
Types of chromosome mutations
• Chromosomal rearrangement
– Structure is altered
• Aneuploidy
– Abnormal number of chromosomes
– Missing one or more/having one or more extra
• Polyploidy
– 1 or more additional sets of chromosomes
Chromosome rearrangements
• 4 types
– Duplications
– Deletions
– Inversions
– Translocations
Duplications
• Section of chromosome is
doubled
• Tandem
– Repeated segment is right
after the original
• Displaced
– Repeated segment is
located elsewhere on
chromosome, or on a
different chromosome
• Reverse
– Sequence is inverted from
the original sequence
Duplications
• Heterozygotes
– During paring of
homologous
chromosomes, duplicated
region loops out
– Offspring receive two
copies of involved genes
from parent with
duplication, and a third
copy of the other parent
• Partial trisomy for all
involved genes
• Alters gene dosage
Gene dosage
Deletions
• Loss of a portion of
chromosome
• Large deletions can be seen
cytogenetically;
microdeletions by FISH
• If the deleted region includes
the centromere, entire
chromosome will be lost
• Usually lethal in
homozygous form
• Heterozygotes
– Normal chromosome must
loop out during pairing
– Partial monosomy for all
involved genes
Deletions - heterozygotes
• Affects gene dosage
• Pseudodominance
– Expression of mutant/recessive phenotype
due to loss of normal/dominant copy
• Haploinsufficiency
– Both copies of the gene are needed to
manufacture adequate amount of gene
product
• One gene doesn’t produce enough for a normal
phenotype
Inversions
• Two breaks in chromosome, then flipped and
reinserted
• Paracentric inversion
– Both breaks occur in one arm
• Pericentric inversion
– Breaks on both arms; centromere is involved
– Can change morphology by altering centromere position
• Effects
– Disruption of a gene – no functional product
– Position effect
• Change in gene position can affect gene expression
Inversion loops
• Chromosomes have to
loop when pairing
• Paracentric inversion
loops
– If crossing over occurs
within loop:
– Creates a dicentric
chromosome and an
acentric chromosome
• Acentric is lost
• Dicentric forms a dicentric
bridge, and breaks
• Nonviable recombinant
gametes
Paracentric inversion loop
Inversion loops
• Pericentric
inversion loops
– Crossing over
within loop creates
recombinant
chromosomes with
duplications and
deletions
• nonviable
Pericentric inversion loops
Translocations
• Rearranges genetic material
to another part of the same
chromosome; or
nonhomologous chromosome
• Nonreciprocal
– Segment moves from one
chromosome to another
• Reciprocal
– Exchange between two
chromosomes
• Effects
– Loss of gene function –
break
– Position effect
– Creation of a
fusion/abnormal protein
Robertsonian translocation
• Between two
acrocentric
chromosomes
– 13, 14, 15, 21, 22
• 2 q arms are joined at a
common centromere
– Forms a metacentric
chromosome if two
chromosomes are same
size
• Small fragment is
usually lost
– Tends to be acentric
Translocations
• Translocated chromosome is named after
the chromosome that is the origin of the
centromere
• Heterozygotes have one normal copy of a
chromosome, and one translocated one
– During meiosis, all 4 chromosomes will
associate
– Can segregate 1 of 3 ways
Translocation segregation
• Alternate
– Both normals go to one
pole; both translocated go
to the other
• Balanced; viable
• Adjacent 1
– Each pole gets one normal,
and the opposite
translocated
– Partial monosomies/partial
trisomies
• inviable
• Adjacent 2
– Each pole gets both the
normal and translocated of
the same chromosome
– Inviable; rare
Translocation segregation
Fragile sites
• Under certain
conditions/culturing
techniques,
chromosomes
develop
breaks/restrictions at
particular locations
• Now routinely tested
for by FISH analysis
Aneuploidy
• Abnormal number of chromosomes
– Caused by:
• Loss of chromosome during cell division; random error or
loss of centromere; nondisjunction
• Robertsonian translocation
• Types
– Nullisomy 2n – 2 – missing both members of a
homologous pair
– Monosomy 2n – 1 – missing one chromosome
– Trisomy 2n + 1 – one extra chromosome
– Tetrasomy – 2n + 2 – two extra chromosomes of the
same type/homologous
Aneuploidy
• Alters phenotype dramatically
– Often lethal if constitutional
• Can see elaborate abnormalities in tumor cells
– X inactivation in mammals takes care of extra Xs, so
not as severe
• Down syndrome
– Primary
• 3 free copies of #21
– Familial
• Extra copy due to translocation
– Can be involved in Robertsonian translocation
– Parent can have 45 chromosomes, but have normal phenotype
since all genetic material is present
Uniparental Disomy
• Both chromosomes of a homologous pair
from the same parent
• Probably originated from a trisomy
– One chromosome is lost early in development
• Recessive diseases
– One carrier parent and one normal parent can
have an affected child
Mosaicism
• Nondisjunction in later development can
cause “patchiness” – normal cells and
abnormal cells
• Approximately 50% of Turner syndrome
can be mosaics
– 45, XO/46, XX
Polyploidy
• Extra sets of chromosomes
– Triploid – 3n; tetraploid – 4n
• Common in plants – more tolerant of extra sets
of chromosomes
• Autopolyploidy
– Extra set is from same species
• Error in cell division
– Extra chromosome caused pairing problems;
especially with odd numbers
• 3n usually sterile; produce small seeds
– Bananas; “seedless” watermelon
Polyploidy
• Allopolyploidy
– Hybridization between two species
– AABBCC x GGHHII
– F1 generation ABCGHI – not homologous
• Gametes are inviable, but may be able to
reproduce asexually
– Nondisjunction error can lead 2x, which could
then reproduce sexually