Chapter 16: Large-scale chromosomal changes

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Chapter 16 Large-scale chromosomal changes
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Aberrant euploidy (usually polyploidy) and
aneuploidy
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Ploidy levels is typically reflected in cell
size Cell growth dynamics is controlled by
ploidy!! Polyploid plants often make larger
seeds!!
Fig. 16-3
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Types of polyploidy Autopolyploidy
multiple copies of identical chromosome
sets usually develop normally cells are
proportionately larger than diploid Alloploidy
multiple copies of non-identical
(homeologous) chromosome sets includes
genomes of two different species usually
display hybrid characteristics
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Autotriploids routinely generate aneuploid
gametes (usually sterile)
metaphase I
anaphase I
Fig. 16-4
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Autotetraploids are readily generated by
suppressing mitotic spindle
suppresses microtubules
Fig. 16-5
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Autotetraploids routinely generate aneuploid
gametes (infertile)
Meiosis I
goes to either pole
disomic gametes
monosomic trisomic gametes
Fig. 16-6
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Types of polyploidy Autopolyploidy
multiple copies of identical chromosome
sets usually develop normally cells are
proportionately larger than diploid Alloploidy
multiple copies of non-identical
(homeologous) chromosome sets includes
genomes of two different species usually
display hybrid characteristics
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Allopolyploids arise from interspecies
hybridization genome duplication
random segregation of nonhomologous chromosomes
regular segregation of homologous chromosomes
produces amphihaploid gametes (nn)
Fig. 16-7
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Likely origins of modern hexaploid wheat
amphidiploid larger kernel !
amphitriploid larger-still kernel !!!
Fig. 16-9
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Aneuploidy extra or missing chromosomes
(less than an entire haploid set) Examples m
onosomy 2n 1 (one chromosome has no
homolog) trisomy 2n 1 (three homologs
for one chromosome)
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Aneuploidy arises from meiotic nondisjunction,
forming aneuploid gametes/spores
Fig. 16-12
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Aneuploids produce aneuploid gametes/spores
Fig. 16-14
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Viable human aneuploids are mostly limited to the
smallest chromosomes and to the sex
chromosomes Examples trisomy-21 Down
syndrome XO (no Y) Turner syndrome primarily
female only viable human monosomic XXY
Klinefelter syndrome primarily male
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Frequency of non-disjunction aneuploidy correlates
with maternal age
Fig. 16-17
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Down syndrome numerous, diverse
manifestations (typical genic imbalance syndrome)
Fig. 16-16
monosomy and large-chromosome trisomy are
developmental lethal Exception sex chromosome
aneuploid syndromes are relatively mild.......
Why?
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Dosage compensation mechanism for making
X-linked gene expression equal in females (with
two X chromosomes) and in males (with one X
chromosome) In mammals only one X chromosome
is active in each cell In Drosophila the
activity of each X-linked gene copy is reduced
in multi-X cells Thus, genic imbalance problems
are reduced in commonly occurring sex chromosome
aneuploids
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• Chromosomal rearrangements
• Double-strand DNA break rejoining
• Ends are very transient and rapidly join
  together
• Rejoining may restore the chromosome or may
  result in any imaginable combination of joined
  fragments
• Crossingover between repetitive DNA elements
• Recovery of products follows certain rules
• 1. Each product must have no more nor less than
  
• one centromere
• (a mitotic and meiotic essential)
• 2. Viability of the gametes/spore/zygote
  following
• meiosis is subject to gene balance effects
• (segmental aneuploids are usually poorly viable)

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Types and origins of chromosomal rearrangements
Unbalanced rearrangements
Balanced rearrangements
Fig. 16-19
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Loops are seen in synapsed homologs in
deletion heterozygotes
Deletions behave genetically as multi-gene
loss-of-function mutations
Fig. 16-20
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Deletions are useful in physically mapping
small chromosome regions
Fig. 16-21
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Duplications arose in the Saccharomyces genome
by ancestral polyploidy
Evidence Completion of genome sequences of S.
cerevisiae and close relatives
Bioinformatic comparison revealed
duplication of three different, large
segments of S. cerevisiae genome (not in
relatives) Apparently derived from
whole-genome duplication, followed by loss of
most duplicated chromosomes
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Duplications arose in the Saccharomyces genome
by ancestral polyploidy
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Types and origins of chromosomal rearrangements
Unbalanced rearrangements
Balanced rearrangements
Fig. 16-19
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Consequences of inversions on neighboring genes
Gene order changed, but all genes intact May
result in no/little effect on genes (unless
control regions are mutated) LOF mutation of
C LOF mutation of A and D (can also bring
genes under control of novel enhancers and other
regulatory elements)
Fig. 16-26
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Meiotic consequences of inversion heterozygosity
Fig. 16-27
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• Crossingover within inversion
• loops results in chromosome
• duplication/deletion
• Pericentric inversion
• Crossover products yield inviable gametes/progeny

Only non-crossover products are transmitted
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• Crossingover within inversion
• loops results in chromosome
• duplication/deletion
• Paracentric inversion
• Dicentric bridge formation
• Crossover products yield inviable gametes/progeny

Only non-crossover products are transmitted
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Meiosis in translocation heterozygotes can
result in duplication/deletion gametes/spores
Only non-crossover products are transmitted
Fig. 16-30
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A variety of cancers arise from somatic
translocation events involving proto-oncogenes
no MYC expression in lymphocytes
Ig expression in lymphocytes
MYC expression in lymphocytes
signal-dependent ABL protein kinase
constitutive protein kinase
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Incidence of chromosome mutations in human births
Spontaneous chromosome anomalies are
common Vast majority are eliminated in utero
Fig. 16-37