Chromosome Mutations: Variation in Number and Arrangement
Karyotypes
 Karyotypes are typically prepared using Giemsa staining to reveal G bands (rich in AT base pairs)
Chromosome mutations
1. Aneuploidy
2. Polyploidy
3. Chromosome rearrangements
Aneuploidy
 Aneuploidy - change in the number of individual chromosomes
 Chromosomes may be lost during mitosis or meiosis
 Nondisjunction in meiosis or mitosis
Types of aneuploidy
1. Nullisomy - missing both copies of a homologous pair
2. Monosomy - missing one copy of a homologous pair
3. Trisomy - having one extra copy of a chromosome
4. Tetrasomy - having two extra copies of a chromosome
Aneuploidy in humans
 Aneuploidy in humans usually leads to spontaneous abortion
 Only ~2% of all fetuses with a chromosome defect survive to birth
 Sex-chromosome aneuploidy
o
Probably more tolerated because of X inactivation and the fact that there
are so few genes on the Y chromosome
 Autosome aneuploidy
o
Much less common than sex-chromosome aneuploidy
 Trisomy 21 - may only contain ~300 genes
o
~92% of individuals with Down syndrome have primary Down syndrome
o
~75% of the nondisjunction events are maternal in origin (usually at
anaphase I)
Other autosomal aneuploids
 Edward syndrome - extra 18
 Patau syndrome - extra 13
Polyploidy
 Polyploidy is common in plants, rare in animals
Autopolyploidy
 All sets are from the same species
 Can occur due to errors in meiosis or mitosis
 An autotriploid will always demonstrate unbalanced gametes after meiosis
 Therefore, most triploids do not produce viable offspring
Allopolyploidy
 Arises from the hybridization of two species
 Interestingly, in plants, the hybrid is often viable
 Sometimes, the hybrid is actually more vigorous than either parent
Chromosome rearrangements
 Deletions
 Duplications
 Inversions
 Translocations
Deletions
 Loss of a chromosomal segment
 There can be different causes
 For heterozygotes, tetrad formation in prophase I can look pretty weird
 The consequences of the deletion depend on the location and the extent of the
deletion - primarily which genes are lost
o
Loss of the centromere will prevent proper chromosome segregation
o
Most deletions are homozygous lethal
o
However, even heterozygotes may exhibit multiple defects
o
Imbalance of gene products
o
Recessive alleles may be expressed if the wild-type allele is lost pseudodominance
o
For some genes, there must be two copies for proper function
o
If one copy is not sufficient - haploinsufficient gene
o
Loss of function with haploinsufficient genes is dominant
 A deletion of a small portion at the terminus of chromosome 5 causes Cri du Chat
Chromosome rearrangements
 Duplications
o
Tandem duplications - The duplicated region is adjacent to the original
segment
o
Displaced duplication - The duplicated region is located away from the
original segment
o
Reverse duplication - The duplicated region is inverted relative to the
original segment
 Tandem duplications are usually the result of unequal crossing over
o
Chromosome duplications can show some interesting phenotypes
o
Having extra copies of genes may upset the careful balance required for
proper development
o
On the other hand, having extra copies of genes may also remove the
constraints on maintaining functional copies of essential genes
 This may allow the evolution of genes
Inversions
 Paracentric inversions do not include the centromere
 Pericentric inversions do include the centromere
 Effects
o
Sometimes there is no effect
o
Sometimes an inversion may interrupt a gene
o
Other times, expression of genes can be altered - position effect
 Inversions can lead to interesting results during meiosis
Translocations
 Exchange of DNA between non-homologous chromosomes
 There are issues during meiosis leading to non-viable gametes
 In a Robertsonian translocation, the breaks occur at the ends of the short arms
o
The resulting longer chromosome is usually stable but the smaller
chromosome is not
 Effects
o
Can interrupt a gene
o
Position effects
 We can track translocations throughout evolutionary history
 Some characteristic types of translocations can lead to abnormal chromosome
numbers
o
~4% of individuals with Down syndrome have 45 chromosomes with an
extra copy of a portion of chromosome 21
o
Familial Down syndrome because it has a tendency to run in families
o
Usually this is the result of a Robertsonian translocation
o
Individuals with this translocation (translocation carriers) do not have
Down syndrome because they have the long arms of both chromosomes
o
They do have an increased chance of producing children with Down
syndrome
o
The most common translocation is between chromosomes 14 and 21
Fragile sites
 Some chromosomes develop fragile sites - constrictions or gaps
o
In fragile-X syndrome, this is due to an increased number of CGG
trinucleotide repeats
o
Other fragile sites do not show repeated sequences
Mosaicism
 If nondisjunction occurs in mitosis early in a developing individual, this can lead to
mosaicism
o
Turner syndrome - ~50% show variable expressivity for Turner
syndrome
o
They are mosaics of 45,X/46,XX and the severity depends on the time of
the nondisjunction and where the 45,X cells are located
 Things can get really strange in Drosophila
o
Like XX/XO mosaics - gynandromorphs
o
There can be extreme cases