1Chromosomal mutations

• 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

2Change 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

3Human 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

4Sex 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

5Other 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.• http://en.wikipedia.org/wiki/XYY_syndrome• http://www.pathguy.com/xyy.htm

6Human aneuploidies-2

• 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.

7Complications in understanding how Trisomy 21 comes about

• 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.

8Other human trisomies• 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

• 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

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10Polyploidy and monoploidy• 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:

• 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

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12Polyploidy results from

endoreduplication

• 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...

FISH of allopolyploids13

http://www.shigen.nig.ac.jp/rice/rgn/vol13/image115.gif

http://books.google.com/books?id=KGXjKuOJm5YC&pg=PA196&lpg=PA196&dq=crocus+allopolyploid&source=web&ots=SO7O-11vJf&sig=zK6mZG8A4--sBEpLQhAZ50sSBTs#PPA197,M1Figure 5.32

14Monoploids can be used in plant breeding

• 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.

15Plant breeding continued

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

16Chromosome irregularities of various kinds cause problems in humans.

• Excerpt from table; this table will be on the next exam.

Table 9.2: Chromosomal abnormalities per 100,000 recognized human pregnancies

Abnormality Spontaneous abortions live births15,000 85,000

Total 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.

17An example from the table

Table 9.2: Chromosomal abnormalities per 100,000 recognized human pregnancies

Abnormality Spontaneous abortions live births15,000 85,000

Triploid 1275 0

Total 7500 550

Of the 15,000 pregnancies that ended in spontaneous abortions, 1275 of them were found to be triploids.

What percent is that?

What percent of all the pregnancies is that?

What percent of live births were triploids?

HINT: questions like this on the following exam?