chapter 10 part 2 Flashcards
mutations that result in loss or gain of whole chromosomes or chromosome segments can produce what?
severe abnormalities due to gene dosage imbalances
terminal chromosome deletion
- single break point
- detachment of one part of chromosome arm
chromosome break point
both DNA strands severed at a location called a chromosome break point
where can broken chromosome ends adhere to
- other broken ends
- termini or other intact chromosomes
- each other
broken fragment in terminal deletion contains what?
telomere and some genetic material
what happens if broken chromosome fragment is acentric?
will likely be lost during cell division as it can’t attach to spindle apparatus
partial deletion heterozygote
one normal and one terminally deleted chromosome
ex. of terminal deletion
Cri-du-chat syndrome
Cri-du-chat syndrome
caused by loss of 5p15.2-5p15.3
- infants produce distinctive cat-cry sound
interstitial deletion
loss of an internal portion of a chromosome
- 2 chromosome breaks
ex. of interstitial deletion
WAGR syndrome
WAGR syndrome
series of conditions caused by deletion of multiple genes on chromosome 11
what can unequal crossover result in
partial duplication or partial deletion
partial duplication heterozygote
one normal and one duplication homolog
partial deletion heterozygote
one normal and one deleted homolog
true or false: unequal crossover occurs often
false
when does unequal crossover usually occur
when repetitive regions of homologs misalign
ex. of unequal crossover
Williams-Beuren syndrome
is Williams-Beuren syndrome partial deletion or partial duplication
partial deletion
Williams-Beuren syndrome
partial deletion heterozygotes for segment of chromosome 7 that contains copies of gene PMS (A and B)
- unequal crossover leads to one nonfunctional hybrid PMSA-PMSB gene
when do homologs synapse
prophase 1
what can be observed through microscopic observation during prophase 1
regions of chromosome duplication and deletion
a large deletion or duplication creates what
area of mismatch between altered chromosome and normal homolog
unpaired loop
created by large deletion/duplication, which is the part of one homolog missing on the pairing partner
what can large deletions/duplications be detected by
microscopy that reveals altered chromosome banding patterns
can you use microscopy to detect micro-deletions/duplications
no - too small
what is usually used to detect micro-deletions/duplications
molecular techniques such as FISH (fluorescent in situ hybridization)
- detects presence or absence of particular DNA sequence
chromosome inversion
reattachment of broken chromosome fragment in wrong orientation
chromosome translocation
reattachment of broken chromosome fragment to non homologous chromosome
paracentric inversion
if centromere is outside of inverted region
pericentric inversion
if centromere is within inverted region
inversion heterozygotes
have one normal and one inverted homolog
crossing over that occurs within a paracentric inversion results in:
- dicentric chromosome: contains 2 centromeres
- acentric fragment: doesn’t contain centromere
what happens to dicentric chromosome in paracentric inversion
pulled toward both poles of cell, eventually breaks at random point
- both produces of break are missing genetic material
what happens to acentric fragment during paracentric inversion
lost because it lacks centromere and can’t attach to spindle during division
crossing over within pericentric inversion results in:
both duplicated and deleted regions in both of the recombinant products
recombination events of paracentrics/pericentric inversions yields:
- 2 normal gametes (non-crossover chromatids)
- 2 abnormal gametes (crossover chromatids)
3 types of translocations
- nonreciprocal
- reciprocal
- Robertsonian
nonreciprocal translations
piece of one chromosome is translocated to a non-homolog and there is no reciprocal event
- one-way transfer
reciprocal translocation
pieces of 2 non-homologs switch places
- two-way transfer
Robertsonian translocations
chromosome fusions - involve fusion of 2 non-homologs
- reduction in total chromosome number
in heterozygotes for reciprocal balanced translocations, none of four chromosomes has what?
fully homologous partner
what is formed at metaphase 1 of meiosis in reciprocal balanced translocations
unusual cross-like structure
what are translocations heterozygotes in reciprocal translocations
semi-sterile
why are translocations heterozygotes in reciprocal translocations semi-sterile
only alternate segregation leads to normal gametes
- even only 1/2 of them are normal
when 2 pairs of chromosome fuse by Robertsonian translocation, number of chromosomes drops to
2n-2
ex. of Robertsoninan translocation
familial Down Syndrome
familial Down Syndrome
Roberstonian translocation between chromosome 21 and usually 14
chromatin
DNA and associated proteins of a chromosome
what is chromatin organization essential for
- gene regulation
- segregation
chromatin =
1/2 DNA
1/2 proteins
protein =
1/2 histone proteins
1/2 non-histone proteins
histone proteins
small basic proteins that tightly bind DNA
non-histone proteins
rumination proteins that are very diverse and perform a variety of functions
5 major histone proteins
- H1
- H2A
- H2B
- H3
- H4
nucleosome core particle
fundamental units of histone protein organization with 2 molecules each of histones (H2A, H2B, H3, and H4) that form ocatmer
core DNA
~146 bp long span of DNA that wraps around each octamer to form a nucleosome
nucleosome assembly
- histones H2A/B assemble into dimers
- histones H3/H4 assemble into dimers
- 2 H3/4 dimers = tetramer
- 2 H2A/B dimers associate with tetramer to form octamer
first level of DNA condensation
wrapping of DNA around the nucleosome
- compacts DNA 7x
electron micrographs of DNA in least condensed state show:
10-nm fiber
- beads-on-a-string
linker DNA
variable-length string between nucleosomes
linker DNA length in Saccharomyces cerevisiae
13-18 bp
linker DNA length in Drosophila
35 bp
linker DNA length in humans/mammals
40-50 bp
linker DNA length in sea urchins
110 bp
when is the 10-nm fiber not observed
under normal cellular conditions
what is observed instead of a 10-nm fiber
30-nm fiber (6 times more condensed)
how does 30-nm fiber form
when 10-nm fiber coils into a solenoid structure
solenoid structure
6-8 nucleosomes per turn, histone H1 stabilizes solenoid
second level of DNA condensation
30nm fiber - solenoid
when does chromatin become maximally condensed
during metaphase of mitosis
interphase chromosomes have variably sized loops of 30-nm fibers that form a
300-nm fiber
chromosome shape depends on the
chromosome scaffold
chromosome scaffold
composed of filamentous, non-histone proteins
MARs (matrix attachment regions)
where chromatin loops (20-100kb) are anchored to chromosome scaffold by non-histone proteins
metaphase chromatin is compacted _____________ compared to the 300-nm fiber
250-fold
what does chromosome compaction allow for
efficient separation of chromosomes at Anaphase
chromatin loops formed during condensation play role in what?
regulation of gene expression
where does active transcription usually occur
in segments of loops away from MARs
- DNA near MARs less accessible
as the replication fork passes, what must happen to nucleosomes
must break down into component parts and release DNA
after replication, what happens to the nucleosomes?
reassembled, but need 2X now
nucleosomes present after replication typically contain:
- some old histone proteins (may have epigenetic marks like methyl/acetyl)
- new histone proteins
- H3/H4 tetramers reassociated randomly with one of sister chromatids
- H2A/B dimers disassemble and are reassembled from both old/new histones
