M2 L9: chromosomal mutations Flashcards
chromosomal mutation
heritable changes at the chromosomal level (change in structure or number)
euploidy
having an even multiple of N chromosomes (any number of full sets)
aneuploidy
having an extra or one less copy of a chromosome (or multiple) - not an exact multiple of N
nondisjunction
chromosomes not separating in meiosis I or II –> makes aneuploid gametes
monosomy
when a diploid organism is missing one copy of a chromosome
trisomy
when a diploid organism has an extra copy of a chromosome
polyploidy
karyotypes that are even multiples of N (full sets) but more than 2N
how do we get variation in chromosome number (aneuploidy)?
nondisjunction (or mitotic errors –> mosacis)
how are the effects of nondisjunction different for meiosis I and II
nondisjunction in meiosis I –> 2 gametes have an extra chrom, 2 gametes missing one
in meiosis II –> 1 gamete has an extra chrom, 1 gamete missing one, 2 are normal
most common monosomy karyotype
2N-1
viable monosomy in humans and drosophila and why
turner syndrome (X): would only have one X active anyway (all others = barr bodies)
chromosome IV: very small, only 5% of genes, still smaller than normal
why is monosomy usually lethal in animals
expression of recessive lethals that would normally be masked by dominant alleles
improper gene dosage and no way of compensation
effect of monosomy in plants? exceptions?
tolerate in autosomes better than in animals but still develop smaller/less viable
pollen very sensitive to meiotic nondisjunction because normally haploid and require development before fertilization; if missing a chromosome –> can’t develop enough to fertilize egg
typical trisomy karyotype
2N+1
how is trisomy tolerated in plants and animals/yeast/humans
better than monosomy as long as the chromosome is small
still poorly tolerated in humans
plants tolerate it well
can be advantageous in yeast
examples of advantageous trisomies in yeast? Why are they advantageous?
S cerevisiae: trisomy 3 –> better heat tolerance
candida albicans (trisomy 5) and cryptococcus (trisomy 1): better tolerance of azole drugs
all caused by increase in gene dosage for relevant genes
only viable autosomal trisomy in humans? who discovered the syndrome? how common is it? phenotypes?
trisomy 21
down syndrome
langon down
1/800 live births
short stature, intellectual disability, heart malformations, decreased F fertility, M usually sterile
Which parent contributes the extra chromosome for down syndrome/how do we know
The mother
Rate of trisomy 21 associated with maternal age but not paternal age
what trisomies have been observed in humans? Which survive to term? Which are compatible with life?
All have been observed
5 survive to term: X, Y, 13, 18, 21
3 compitable with life: XXX, XYY, 21 (triplo X, jacobs, down)
what trisomies are compatible with human life for usually only a few weeks?
13: patau syndrome
18: edwards syndrome
Why are monosomes less common among miscarried fetuses compared to trisomies? What’s expected?
Should be obs in equal ratios bc for every gamete with an extra chromosome, there is a gamete with a missing chromosome
monosomy fetuses don’t even develop enough to be recovered, but trisomy fetuses do
what’s autopolyploidy? is it more common in plants or animals?
adding full sets of N to organisms within a species
more common in plants, has happened in lizards, fish, amphibians
what are the three ways to get a triploid (autopolyploidy, 2N –> 3N)
1) nondisjunction of all chrom in meiosis –> diploid gamete that unites with haploid gamete
2) two sperm and one egg
3) diploid mates with a tetraploid (diploid makes N gametes, tetraploid makes 2N gametes)
how to make a tetraploid
one main way
duplication without division (zygote duplicates DNA but then doesn’t divide)
impact of autotetraploidy? (making a tetraploid via autopolyploidy) why?
tetraploid mates w/ normal diploid and makes a triploid
meiosis in triploids fails
triploid is reproductively isolated –> instantaneous speciation
why does meiosis fail in triploids
3rd pair of homologs separate in meiosis 1, but in order to make balanced gametes, one homolog (for every chromosome) must go to each daughter cell in meiosis I –> very unlikely so gametes usually aneuploid
probability of making a haploid or diploid gamete? probability of making a haploid gamete? probability of making a diploid gamete? where does this come from?
(1/2)^(N-1)
1/2 x (1/2)^(N-1)
1/2 x (1/2)^(N-1)
extra homologs assort independently from each other (no way to make 3rd maternal and paternal homologs go to opposite daughters)
how are polyploid plants produced and why? what are some examples
propagated asexually/cloning bc meiosis usually fails (same reason as in triploids)
also larger than diploids
bananas and winesap apples
why are polyploid yeast cells larger than diploids
more than 2 copies of each chrom (being polyploid) decreases production of cyclins in G1 phase of cell cycle –> cell grows larger before division is triggered
what’s allopolyploidy
combining full sets (N) from two different species
are allopolyploidy hybrid offspring sterile? Why/why not?
Would expect them to be but can go through whole genome duplication –> all chrom from both species’ haploid sets have a homolog –> can do meiosis
is allopolyploidy more common in plants or animals and why
more common in plants
hybridization between distantly related animal species is rare
what’s the phenotype of allopolyploid hybrid offspring? common allopolyploid plants?
can have some traits from each parent or a completely new phenotype
gossypium hisutum (hybrid of old/new world cotton)
sporobolus anglicus (hybrid of 2 grasses, new phenotype)
Types of mutations within individual chromosomes? What causes them?
duplications, deletions (terminal and intercalary), inversions (peri and paracentric), translocations (reciprocal, nonreciprocal, robertsonian)
all are from chromosomes repairing breaks
what’s a duplication
doubling genetic material on a chrom
what’s a deletion
losing genetic material on a chrom
terminal is from the end, intercalary is from the middle
what are translocations
reciprocal: genetic info exchanged between non homologs (like crossing over with nonhomologous autosomes)
non reciprocal: genetic info transferred from one chrom to another
what are inversions
gene order reversed for a segment of a chromosome
paracentric does not involve centromere, pericentric does
what 2 things must be true for a chrom mutation to be heritable
must be in the germ line
must change the original composition or gene content of the chromosome
how many breaks do deletions require? what part of the chromosome is kept? how do they synapse? what’s the effect on phenotype?
terminal = 1 break
intercalary = 2 breaks
keep part with centromere
homolog w/o deletion forms a deletion loop (compensation loop)
can lead to expression of recessive lethals or deleterious alleles
effect can change based on haplosufficiency/insuficiency
human disorder caused by a deletion? where is the deletion? what is the phenotype? how rare is it?
crit du chat
terminal deletion on chromosome 5
size of deletion determines severity, usually intellectual disability, malformation of glottis and larynx –> cry sounds like a cat
1/25,000-50,000 live births
how do chrom with duplications synapse? what are the 2 main ways to get duplications
chrom w/ duplications forms compensation loop
1) unequal crossing over in meiosis (loci not lined up)
2) replication error in mitosis
what types of genes are normally present as duplications/many copies
rRNA and rDNA clusters (for making ribosomes bc we need lots of them)
phenotypic consequence of duplications in yeast?
duplications in CUP1 gene –> make more proteins (sequester copper ions in the cell/prevent oxidative damage)
how many breaks do inversions require? how do they synapse? how many viable chrom are produced after recombination?
2 breaks
inverted chrom forms inversion loop
paracentric doesn’t involve centromere –> 1 normal non recomb, 1 dicentric recomb with dup and del, 1 acentric recomb with dup and del, 1 inverted non recomb
pericentric does involve centromere –> 1 normal non recomb, 1 inverted nonrecomb, 1 recomb with dup and del, 1 recomb with dup and del
how do inversions affect recombination?
don’t prevent recombination but make it so recombinants at those loci are not expressed in hets (they’re inviable)
what are robertsonian translocations
small arms of two nonhomologous chromosomes are lost, long arms fuse and form one chromosome
effects of robertsonian translocations (phenotypes, synapsis, and gametes/meiosis)
familial down syndrome (inheriting a 21 from each parent and a translocated 21 –> down syndrome)
cause abnormal synapsis
chance of semi sterility from making unbalanced gametes (have duplications and missing genes) bc chromosomes w/ translocations still assort independently
how can inversion and translocation change gene expression? example?
put genes under dif promoters/closer to promoter –> change amount of expression
2 translocations and an inversion in SSU1 s cerevisae gene –> more SSU1 expression = more membrane bound sulfite pumps = more sulfite resistance
Explain how CUP1 duplications can be adaptive for yeast. Is the benefit of these mutations dependent on the environment? Why or why not?
CUP1 gene produces proteins that sequester copper ions in the cells and prevent them from causing oxidative damage. Duplication = more of these proteins = more protection from copper ions. The benefit depends on the environment because if the yeast were not in an environment frequently sprayed with copper, it would not be advantageous to them.
Suppose the offspring of two inversion heterozygotes (who harbor the same inversion) receives an inverted copy of a chromosome from both its mother and father. Will meiosis be affected?
No, since both of the offspring’s chromosomes have the same inversion, they will be able to synapse and recombine with each other.
Explain the meiotic consequences of a translocation in the context of independent assortment.
A translocation het will be semisterile. Following independent assortment, 50% of their gametes will not be balanced and will lack a full haploid set of genes.
What frequency would you expect a Down syndrome affected parent to produce Down syndrome afflicted offspring?
50% because the extra copy of 21 has to go to one of 2 daughter cells in meiosis I
