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
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
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
Other sex chromosome aneuploidies
Some phenotypically normal
Others, sterility, mental retardation
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.
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
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
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.
9.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
Polyploidy 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
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 fromendoreduplication
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
Monoploids 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.
Plant 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.
Chromosome irregularities of various kinds cause problems in humans.
Excerpt from table; this table will be on the next exam.
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.
An example from the table
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 next exam?
Changes in chromosome structure
part is missing.
section is flipped
piece attached to another chromosome.
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
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:
Red-green color blindness
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
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.
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.
Paracentric and pericentric inversions
Problems with inversions in meiosis
Duplications, deletions, and dicentric and acentric chromosomes can result from funny pairing and subsequent crossing over.
A piece of a chromosome winds up attached to another chromosome. Could be a swap (reciprocal) or not.
Translocations occur between non-homologous 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
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.
Cases of inherited Down syndrome involve translocation of part of Chromosome #21 to, typically, #14.