Eukaryotic Chromosome Abnormalities: Changes to Chromosome Structure + Number Flashcards
Define aneuploidy
‘not euploid’
the addition or removal of a chromosome which alters the euploid number (n+1 or n-1 if one chromosome pair is affected)
caused by nondisjunction
Define polyploidy
the presence of three or more sets of chromosomes in the nucleus of an organism (ex. 3n, 5n, 6n, etc.)
common in plants
What is the difference between aneuploidy and polyploidy?
Aneuploidy is a change in the number of chromosomes in a single set
Polyploidy is a change in the number of sets of chromosomes
Define monosomic
an organism/fertilized egg with 2n-1 ploidy that results in an aneuploid gamete fusing with a normal haploid gametes at fertilization and giving the organism a single copy of one of the chromosomes rather than a homologous pair
Define trisomic
an organism/fertilized egg with 2n+1 ploidy that results in an aneuploid gamete fusing with a normal haploid gametes at fertilization which gives an organism 3 of one of the chromosomes rather than a homologous pair
Describe nondisjunction
the failure of chromosomes and sister chromatids to properly disjoin/detach during anaphase of meiosis which causes abnormalities in chromosome numbers
How does nondisjunction lead to monosomy?
Nondisjunction in meiosis causes aneuploidy (different number of chromosomes in a set) and when an aneuploid gamete fuses with a regular gamete, there’s only a single copy of one of the chromosomes = monosomy
How does nondisjunction lead to trisomy?
Nondisjunction in meiosis causes aneuploidy (different number of chromosomes in a set) and when an aneuploid gamete fuses with a regular gamete, there’s three copies of one of the chromosomes = trisomy
Describe where nondisjunction occurs during meiosis I
Nondisjunction in meiosis I causes the failure of homologous pairs to be pulled apart during anaphase I which results in both homologs moving to the same side of the pole = a different number of chromosomes for that set in both cells
Describe where nondisjunction occurs during meiosis II
Nondisjunction in meiosis II causes the failure of sister chromatids to be pulled apart during anaphase II
What gametes would be produced from nondisjunction in meiosis I and II in a heterozygous individual?
Either monosomic (2n-1) or trisomic (2n+1)
Why are half of a trisomic organism’s gametes (offspring) aneuploid?
Because half of the gametes produced during meiosis were effected by nondisjunction
Why are aneuploids often not as viable as polyploids?
the chromosomes are not distributed equally and there is missing genetic material
What does it mean to be heterozygous for a chromosomal rearrangement?
one chromosome of a pair has a mutation resulting from chromosome breakage such as translocation, deletion, inversion, or duplication and one of the chromosomes is normal
Describe a deletion mutation
A mutation that results from the loss of part of a chromosome
Can be caused by chromosome breakage
What are the two results of deletion mutations?
terminal
interstitial
Describe terminal deletion
Chromosome breakage that results in the detachment of all or part of one chromosome arm
Describe an interstitial deletion
chromosome breakage that leads to the loss of an internal portion of a chromosome
Why are some deletion mutations lethal when homozygous?
if both chromosomes in a homologous pair are missing pieces of the genetic material, essential genes may be deleted and will not be transcribed and translated which may lead to an unviable organism
Why are some deletion mutations lethal when heterozygous?
deletion can cause gene dosage problems and if the organism is highly sensitive to changes in gene dosage, having deletion mutations in one chromosome can lead to death
Why are recombination frequencies lower in organisms heterozygous for a deletion?
recombination cannot occur in the region of the chromosome that forms a deletion loop (where deletion has occurred
Why do deletion heterozygotes form loops when homologs pair in meiosis?
organisms that are heterozygous for deletion mutations have one normal homolog and one partially deleted homolog so there is a mismatch in genetic material when they pair
Describe a duplication mutation
An unequal crossover event results in some genetic material of one homolog being duplicated
Why are recombination frequencies higher in organisms that are heterozygous for a duplication?
the chromosome with the duplication has extra genetic material so there is more space available for crossover
Why do duplication heterozygotes form loops when homologs pair in meiosis?
organisms that are heterozygous for duplication mutations have one normal homolog and one partially duplicated homolog so there is a mismatch in genetic material when they pair
Describe an inversion mutation
A mutation that occurs when chromosome breakage leads to the reattachment of DNA strands at the wrong broken ends, causing the chromosome to be in the wrong orientation
Why are some inversion mutations lethal when homozygous?
if the inversion includes essential genes, a homozygous individual will not survive
Why do viable inversion homozygotes pair and recombine normally during meiosis?
Why do viable inversion homozygotes have different linkage maps than organisms with wild-type chromosomes?
the gene order will be reversed in the area of inversion so the map distances between genes will also differ when compared to a wild-type chromosome
Why are some inversion mutations lethal when heterozygous?
with pericentric inversion (crossover inside the inversion region), the recombinant gametes will have a duplicated and deleted region and may not survive due to abnormal dosages of some of the genes
with paracentric inversion (crossover outside the inversion region), recombinant gametes will have altered gene dosage and an acentric and dicentric centromere which cause losses and breakages of chromosomes –> lethal
Why do inversion heterozygotes form loops when homologs pair in meiosis?
When a normal chromosome pairs with its inverted homolog, the genetic material will be mismatched and will cause a loop
What is the result of crossover within the inversion loop in a heterozygous organism?
duplications and deletions in the recombinant chromosomes
Why does crossover within the inversion loop of an organism that is heterozygous for an inversion result in non-viable recombinants?
pericentric inversion results in nonviable offspring because it causes duplications and deletions in chromosomes of the gamete which changes the gene dosages and can be lethal
Why do inversion heterozygotes have reduced recombinant frequencies?
the inversion loop forms during meiosis to maximize pairing but if crossover occurs in the inversion loop, duplications and deletions of the chromosomes occur and this leads to nonviable recombinant chromosomes
crossovers do occur, but they produce nonviable recombinants that are not observed in progeny
Why do some inversion heterozygotes have reduced fertility?
if there is a large inversion, any crossover that occurs will produce two viable and two nonviable gametes, so ~half of the gametes are lost
Describe a reciprocal translocation mutation
A mutation that occurs when chromosome breakage leads to the reattachment of broken DNA strands to a non-homologous chromosome (ie., a completely different chromosome with different genetic material)
Why do reciprocal translocation homozygotes pair and recombine normally during meiosis?
Why do reciprocal translocation homozygotes have different linkage maps than wild-type organisms?
the gene order is rearranged in translocated chromosomes because fragments of the chromosome are moved around
Why do reciprocal translocation heterozygotes form cross-shaped structures when homologs pair in meiosis?
because none of the four chromosomes has a fully homologous partner
What are the 2 common segregation options/patterns for a translocation heterozygote in meiosis I?
adjacent-1
alternate
Describe adjacent-1 translocation
one normal and one translocated chromosome move to each pole of the cell
Describe alternate translocation
The two normal chromosomes move to one pole of the cell and the two translocated chromosomes move to the other pole
What do mutations resulting in loss or gain of whole chromosomes or chromosome segments produce? Why?
produce severe abnormalities due to gene dosage imbalances
What can cause changes to chromosome structure?
chromosome breakage or other events
What are the 4 major changes to chromosome structure?
loss of chromosome segments
gain of chromosome segments
partial deletion
duplication
Describe what occurs when a chromosome breaks and how this event can cause changes to the structure
when a chromosome breaks, both DNA strands are severed
the broken chromosome ends can adhere to each other, to other broken ends, or to the ends of intact chromosomes
Describe an acentric chromosome fragment
a chromosome fragment that lacks a centromere
What happens if a chromosome breaks and the piece that breaks off is acentric?
it will be lost during cell division because there’s no centromere
What is the result of unequal crossover between 2 homologs?
a partial duplication on one homolog and a partial deletion on the other
What is a partial duplication heterozygote?
an organism with one normal and one duplication homolog
What is a partial deletion heterozygote?
an organism with one normal and one deleted homolog
When are large deletions or duplications detectable?
during prophase I when homologs synapse
When will chromosome breakage not cause any phenotypic changes?
If no critical genes or regulatory regions are mutated and dose-sensitive genes are balanced
What are the 2 types of chromosome inversion? What does this depend on?
paracentric inversion
pericentric inversion
depends on the relative position of the centromere
Describe paracentric inversion
the centromere is outside of the inverted region
Describe pericentric inversion
the centromere is within the inverted region
Describe an inversion heterozygote
an organism with one normal and one inverted homolog
What is the result of crossover that occurs outside of the inversion region in a heterozygous organism?
normal crossover and normal recombination
What is the result of crossovers that occur within a paracentric inversion?
a dicentric chromosome + an acentric fragment
dicentric chromosome is pulled toward both poles of the cell = a dicentric bridge that will eventually break
both products of the break are missing genetic material and the acentric fragment is lost
What is the result of crossover within a pericentric inversion region?
duplicated and deleted regions in both of the recombinant products
What kind of gametes are produced from either paracentric or pericentric inversions?
2 normal gametes (from the non-crossover chromatids)
2 abnormal gametes (from the crossover chromatids)
What are three of the genetic implications of recombination in inversion heterozygotes?
- the probability of crossover within the inversion loop is proportional to the size of the loop
- inversion suppresses the production of recombinant chromosomes (crossover suppression)
- fertility may be altered if an inversion heterozygote carries a very large inversion
What gametes are produced from nondisjunction in meiosis I?
either n+1 or n-1
What does the fusion of gametes produced by nondisjunction in meiosis I and normal gametes (n) result in?
either trisomic (2n+1) or monosomic (2n-1) offspring
How many gametes are affected by a nondisjunction event in meiosis II?
2 of the 4
What gametes are produced from nondisjunction in meiosis II?
2 will be normal (n)
one will be n-1
one will be n+1
T or F: aneuploidy doesn’t affect gene dosage
false! it affects the dosage of all the genes on the affected chromosome
Which organisms are highly sensitive to changes in gene dosages? Which are more tolerant?
animals are usually highly sensitive
plants are tolerant
T or F: humans are not that sensitive to gene dosage changes
false! aneuploids often do not survive
Which types of aneuploidy are viable?
autosomal trisomies of chromosomes 13, 18, and 21
T or F: there are viable autosomal monosomies
false
Are sex-chromosome aneuploidies viable?
yes
How is the rate of nondisjunction related to maternal age?
the rate increases with maternal age
What is Turner Syndrome?
a monosomy of the X chromosome (XO) = no second sex chromosome
What are the 2 types of polyploidy?
autopolyploidy
allopolyploidy
What is autopolyploidy?
the duplication of chromosome sets within a species
What is allopolyploidy?
when chromosome sets of different species are combined
What are the 3 most common causes of autopolyploidy?
meiotic nondisjunction that leads to a diploid gamete (ex. 2n egg + n pollen –> 3n plant)
mitotic nondisjunction that doubles chromosome number
(ex. 2n cell –> 4n cell)
the combination of both
(ex. 2n egg + n pollen –> 3n –> 6n)
What is the result of allopolyploidy?
infertility due to the lack of homologous chromosomes during meiosis (because they come from different species)
What are 2 consequences of polyploidy?
increase in fruit and flower size
decrease in fertility (especially in odd-numbered polyploids) almost all gametes are nonviable
What results in heterozygotes for reciprocal balanced translocations? Why?
an unusual cross-like structure at metaphase I forms as a result of none of four chromosomes having a fully homologous partner
What is the third and more rare chromosome segregation pattern that results from reciprocal balanced translocations?
adjacent-2 segregation occurs when homologous centromeres move together to each pole of the cell
What do the gametes that are produced by alternate segregation contain?
a full haploid set of genes
What do the gametes that are produced by adjacent segregation contain?
two copies of some genes and the complete absence of others
Which pattern of reciprocal balanced translocations results in normal gametes (and therefore normal fertility)?
alternate segregation
What is the fertility of translocation heterozygotes? why?
semi-sterile because only alternate segregation leads to normal gametes
adjacent segregation leads to some absences of genes
