Download Polygenic Traits

Chromosomal mutations
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• A mutation is a change in the DNA
• Generally, mutations are considered at the
gene level, but some types of mutations involve
addition, loss, or change of DNA at the
chromosomal level.
• We basically consider two types of change:
– Change in chromosome number
– Change in chromosome structure
Definition: Autosomes vs. sex chromosomes
Change in chromosome number
• An incorrect number of a particular
chromosome is aneuploidy.
– Correct number is euploidy.
– Only one chromosome is monosomy.
– Three chromosomes is trisomy.
• Plants are more tolerant of aneuploidies
– Animals tend not be be, esp. humans.
• Aneuploidies can be autosomal or X/Y
• Aneuploidies arise from non-disjunction
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Human aneuploidies
• Of sex chromosomes:
– XXY, XYY, XO, XXX
– XO is only human monosomy that is viable.
• Partial monosomy in an autosome
– Cri-du-chat syndrome, 46, 5p• Chromosome # 5 missing part of p arm
• Various anatomic malformations and retardation
• Malformed larynx produces cat-like cry
• About 1/ 50,000 live births
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Sex chromosome aneuploides
• 47, XXY Klinefelter syndrome
– male in appearance, but some feminization; sterile.
– slow to learn, but not retarded.
– XXXY etc. similar, but more severe symptoms
• 45, XO Turner syndrome
– Monosomy, the only one occurring in humans
– female, sterile, short webbed neck, broad chest,
short.
– majority aren’t born
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Other sex chromosome aneuploidies
• 47, XXX
– Some phenotypically normal
– Others, sterility, mental retardation
• 47, XYY
– 1965 study: higher number of inmates with XYY
– revisited: no real correlation with criminal behavior
– taller than average, average IQ
– Possible learning difficulties, highly active, fast
growing as children.
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Human aneuploidies-2
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• Down syndrome or Trisomy 21 (47, 21+)
• Mental retardation (mild to severe), heart defects,
round face, short stature, nice personality.
• Can be inherited when a portion of #21 is
translocated onto another chromosome.
Risk of having a Down
syndrome infant
increases sharply with
the mother’s age,
especially older than 35.
Complications in understanding how
Trisomy 21 comes about
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• Mothers older than 35 have rapidly increasing risk.
– 95% of non-disjunctions occur with the ovum.
• Most Down syndrome babies are born to women
younger than 35 because those are the ages that
most women have children.
• Dogma: all your oocytes are present at birth; meiosis
is arrested in Prophase I and not completed until
adulthood, once a month.
– Conclusion: after 35 years, eggs start to go bad.
– New data: adult mice have egg stem cells, produce
new oocytes. In humans, new eggs from ovary cell
culture.
Other human trisomies
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• Only two : Patau syndrome and Edwards syndrome
– mostly females, 1 in about 8,000 live births.
– Eventually fatal, usually within a year
– Both associated with advanced maternal age
• Patau syndrome Trisomy 13 (47, 13+)
– Med. life expect. 2.5 days, only 5% surviving >6 mo.
– severe neurological problems; facial abnormalities,
malformed organ systems, polydactyly.
• Edwards syndrome Trisomy 18 (47, 18+)
– elongated skull, low malformed ears, webbed neck,
bad hips, heart, and lungs.
– avg age at death = 4 mo. 5-10% live beyond 1 year.
Not just Mom
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• Recent studies show that as men age, the DNA
in their sperm has more mutations and broken
strands
– Increased risk of dwarfism in offspring
– Increased risk of autism
Polyploidy and monoploidy
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• Polyploidy: multiple sets of chromosomes.
• Monoploidy: one set only.
– Haploid means half, not one. If normal is tetraploid
(4), then haploid is diploid!
• Polyploids are common in agricultural crops
– Contain larger cells, larger produce, more vigorous
growth. Even numbers of sets are best.
• Triploids are not so good
– no pairing during meiosis, so sterile
– sterility good: bananas and grass carp
• Plants tolerate polyploidy
– Animals don’t.
Endoreduplication:
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• Mitosis (or meiosis) without cell division doubles
the number of chromosomes.
– Occurs in certain tissues of some animals
– Rare in mammals
– Widespread in plants
– When occurring in reproductive cells of plants, can
result in new species with a new number of
chromosomes
Polyploidy results from
endoreduplication
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• Autopolyploids: result from endoreduplication within
one species.
• Allopolyploids: pollen, ova from 2 different species
combine, then endoreduplication occurs. Commercial
wheat is an allohexaploid.
– Yellow crocus is an allopolyploid
– Stable if meiosis still works
biology.clc.uc.edu/ graphics/taxonomy/plants/s...
Monoploids can be used in plant
breeding
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• How to make a plant with the traits you want:
• Cold shock anthers- this stimulates haploid pollen
grains to begin dividing. Forms an embryoid.
– embryoid is a small mass of undeveloped tissue
that you can grow in culture.
– with monoploids, there is NO masking of recessive
traits as in diploids, so you can see what you’re
getting.
• Convert monoploid to diploid by treating with
colchicine (a microtubule inhibitor)
– messes up mitosis, leads to endoreduplication in
some cells; chromosome number doubles from
mono to diploid.
Plant breeding continued
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Embryoid cultured in agar with
nutrients and w/ plant hormones.
Cells differentiate into roots,
stems, etc and become adult
plant.
Seeds can be collected, and
plant propagated.
http://www.sccs.swarthmore.edu/users/00/aphilli1/cpd/lab/callus.html
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Chromosome irregularities of various
kinds cause problems in humans.
• Excerpt from Table 9.2: Chromosomal abnormalities per
table; this table 100,000 recognized human pregnancies
will be on the
Abnormality Spontaneous abortions live births
next exam.
Total
15,000
85,000
7500
550
•Of 100,000 pregnancies, 15,000 ended in spontaneous
abortion, 85,000 in live births.
•The Table lists various chromosomal abnormalities; roughly
half the spontaneous abortions resulted from chromosomal
abnormalities; only 550 of 85,000 live births had them.
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An example from the table
Of the 15,000
pregnancies that ended
in spontaneous
abortions, 1275 of
them were found to be
triploids.
Table 9.2: Chromosomal abnormalities per
100,000 recognized human pregnancies
Triploid
1275
0
What percent is that?
Total
7500
550
Abnormality Spontaneous abortions live births
15,000
85,000
What percent of all the pregnancies is that?
What percent of live births were triploids?
HINT: questions like this on the next exam?
Changes in chromosome structure
• Deletions
– part is missing.
• Duplications
– extra piece
• Inversions
– section is flipped
• Translocations
– piece attached to
another chromosome.
•
www.slh.wisc.edu/.../Partials/ CoMApr98part.html
ghr.nlm.nih.gov/ghr/info/ img,Duplication
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Deletions are bad
• Deletions mean that DNA is missing
– whatever genes were in that region are gone
– if two copies are needed, there’s trouble
– If the remaining allele is lethal, there’s trouble
– the bigger the deletion, the more likely it will be
serious.
• Deletions often accompany duplications
– Duplications are caused by unequal crossing over
– if some chromosome gets 2, another gets 0
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Duplications
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Part of chromosome is doubled; visible in the banding pattern.
Duplication can increase gene dosage; this is usually harmful.
Duplications often caused by unequal crossing over:
ghr.nlm.nih.gov/ghr/info/ img,Duplication
Red-green color blindness
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•X-linked trait: thus shows up much more often in males.
•Genes for red and green vision are related to rhodopsin, are
very similar to each other, and probably arose from a
duplication event.
•Because they are similar they sometimes line up with each
during meiosis, causing unequal crossing over.
Crossing over can also
occur in the middle of a
gene, causing partial color
blindness.
Duplications can be bad
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• Bar eye in Drosophila
– Flies heterozygous for a duplicated gene have a bar
shaped eye instead of a normal one
• Have 3 alleles total, the normal + the duplicate
– Flies homozygous for this mutation (and thus have
2 extra copies of the gene) have a very small
undeveloped eye.
• Gene dosage issue.
http://www.usask.ca/biology/
genetics/Gene_Action/bareye.jpg
Inversions
A portion of the
chromosome is flipped
relative to the rest.
Most of the problems with
inversion are due to
complicated attempts by
chromosomes to pair up
properly during meiosis.
See your text and next
slide.
http://www.dynagene.com/images/in10ideo.gif
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Paracentric and pericentric inversions
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Problems with inversions in meiosis
Duplications,
deletions, and
dicentric and acentric
chromosomes can
result from funny
pairing and
subsequent crossing
over.
www.mun.ca/.../Drosophila_inversion_loop.htm
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Translocations
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A piece of a chromosome winds up attached to another
chromosome. Could be a swap (reciprocal) or not.
Translocations occur between nonhomologous chromosomes!
Major problem is again pairing of
chromosomes during meiosis, resulting
in extra or missing pieces, leading to
partial monosomies and trisomies.
Semi-sterility: only some gametes good
http://library.thinkquest.org/18258/media/translocation.gif
Non-reciprocal translocations
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Piece of one chromosome breaks off, attaches to another
chromosome. Creates partial trisomies, monosomies, which
are generally fatal.
Robertsonian translocation: fusion of chromosomes near the
centromere. One animation shows two centromeres, the other
shows none. Definition describes fusion of centromeres.
http://www.pdx.edu/~newmanl/Robertsonian.gif
http://www.tokyo-med.ac.jp/genet/chm/rst.gif
Cases of inherited Down syndrome involve translocation of
part of Chromosome #21 to, typically, #14.