Chapter 8: Chromosome Variation

Chromosome Mutations include rearrangements,

Aneuploids, and Polyploids
Chromosome Morphology: Position of the
centromere on the chromosome; 4 types:
Metacentric
Submetacentric
Telocentric
Acrocentric
Karyotyping: complete set of chromosomes
possessed by an organism
the chromosomes are
prepared from actively dividing cells (blood or
bone marrow cells) halted in metaphase
arranged acording to size: in
decending order
Banding: helps distinguish chromosomes
that are similar in shape and size; each
chromosome has its own signature made apparent
by staining
G bands (a): Giesma stain,
rich in adenine-thymine (A-T) base pairs
Q bands (b): quinacrine
mustard
C bands (c): centrometric
heterochromatin
R bands (d): rich in cytosine-guanine base pairs
***See human male karyotpe photo***
Chromosomes Rearrangments Alter Chromosome Structure
3 Categories of Chromosme mutations :
Rearrangements: alters structutre
rearrangments often occur when double stranded
breaks occur within the strands of the DNA molecule, and are incorrectly
put back together in the bodys effort to repair
Aneuploidy: alters number of chromsomes
Polyploidy: one or more complete sets are added (3n, 4n, 5n +)
Four types of chromosomal rearragements
Duplication: a segment of the
chromosome is duplicated
Deletion: segment deleted
Inversion: segment rotated 180
degrees

 Translocation: segment moves from one chromosome to a

nonhomologous chromsome, or to another place on the same chromsome
Chromosome Duplication:
Tandem duplication: a duplicated chromosome region is directly adjacent to the
original segment

Displaced duplication: the duplicated segment is some distance from the original
segment either on the same chromosome or on a different one
Compared to the normal chromosome in the picture above, a
displaced duplication example would be ABCDEFGEF.
Reverse duplication: the sequence of the duplicated segment is inverted relative
to the sequence of the original segment
Example: ABCDEFFEG
Homozygous for duplication: person carries the
duplication on both homologous chromosomes
Heterozygous for duplication: carries duplication of one of
the homologous chromosomes
causes problems at Prophase I of
meiosis: the chromosomes are two different lengths and
can't pair up correctly, causing the chromosome with the
duplication to form a loop that compensates for the
difference in length
the appearance of this loop in meiosis
enables us to detect duplications
Duplications can affect phenotypes
In fruit flies, the Bar region determines the
shape of the eyes.
Normal flies have 1 Bar
region each and have round eyes

have 1
homolog
regions

point example

Heterozygous flies
Bar region on one
and 2 duplicated Bar
(bar mutation) on the other
In humans: (see power

Unequal Crossover leads to Duplications and Deletions

during crossover, duplicated regions of
chromosomes misalign
Unbalanced Gene Dosage
Chromosome region duplication effects
phenotypes because protein production is directly
related to the number of copies of the
corresponding gene
developmental processes require the
interaction of multiple proteins, if one protein
increases and one stays the same due to improper
gene dosage, problems occur
Segmental Duplications: numerous
duplicated sequences in human genome greater
than 1000 base pairs in length
Duplications provide one way for new
genes to evolve
the original copy can provide
the function essential for survival, while the
duplicated gene copy is free to mutate
eventually the duplicated
copy can aquire a mutation that is
beneficial to the organism

Chromosome Deletion
Deletions: loss of a
chromosomal segment

 Large deletions are easily detected because chromosome is noticeably shorter

during pairing in Prophase I of meiosis, normal chromosome loops out the
deleted region of the other chromosome to compensate for length difference

Effects of Deletions
Most people homozygous for chromosomes with deleted regions are lethal all
copies of any essential genes are missing in the deleted regions
The deletion can also include the centromere, keepign the chromsome from
segregating in mitosis and meiosis
For those heterozygous for a deletion:
Imbalances in gene produce: loss of protein product
Pseudodominance: expression of a normally recessive gene if the
dominant gene is deleted (b/c the dominant is not there to mask the recessive)
Haploinsufficiency: a single gene is not sufficient to produce a wild
type phenotype
Effects of Deletions/Duplications in Humans

Chromosome Inversion

 Inversion: Segment is inverted/turned 180 degrees; 2 break points are necissary

if a chromosome originally had segments ABCDEFG, then chromosome
ABCFEDG represents an inversion that includes segments DEF.
depends on the involvement of the centromere in the inversion
Paracentric inversion: centromere not included
Pericentric inversion:
includes the centromere
ex:
ABCDEFG to ADCBEFG
Those with inversions have neither lost
nor gained genetic material, just the order has
changed
Many genes are regulated in a position
dependent manner; change that position and
the gene cant function
known as the Position
Effect

Inversions in Meiosis:
Individuals homozygous: no problems arise during meiosis
Individuals heterozygous:
homologous sequences align only if the two
chromosomes form an inversion loop (a)

reduced recombination in genes located in the

inverted region, as gametes formed result in nonviable offspring
abnormal gametes formed in a pericentric inversion
because of single crossover
if a heterozygous cross over occurs in paracentric inversion:
The crossover occurs in the inversion loop between
the two inner chromatids
This forms a chromosome with 2 centromeres
(dicentric) and one chromosome with no centromere (acentric fragment), and
is as a result lost.

 This is because in anaphase the

centromeres are pulled in opposite directions. This forms a dicentric
bridge on the dicentric chromosome. The bridge eventually breaks.
the inner chromatids in the gametes are abnormal,
with one chromatid with two copies of some genes and the other with none
the one with non is non viable
the outer chromatids (not participating in cross over)
are non recombinants
If a heterozygous cross over occurs in Pericentric Inversion

 There are no dicentric bridges or acentric fragments,

but, two of the chromatids have too many copies of some genes and none of
others
Results in:
one normal non recombinant gamete
(ABCDEFGHI)
one nonrecombinant gamete with
paricentric inversion (ABCFEDGHI)
two nonviable recombinant gametes
to find the first one,
look at the alleles that are inverted (in this case, CDE)
one gamete will have
the alleles before the inversion twice: one before the inversion
section and one after (ABEDCBA)
the other gamete will
have the alleles after the inversion twice: one before the
inversion section and one after (GFCDEFG)
Concept Check 1
A Dicentric Chromosome is produced when crossing over takes place in an individual
heterozygous for which type of chromosome rearrangement?
Paracentric inversion
Chromosome Translocations (TQ: What kind of
Rearrangement is it?)

 Translocation: movement of genetic material between non homologous

chromosomes or within the same chromosome
Differes from crossing over becasue in crossing over there is an
exchange of genetic material between homologous chromsomes
Genetic information is the same, but the order has changed, affecting phenotype
physical linkage between genes that were unlinked on separate
chromosomes before, causing a new gene expression or position effect. Could
become under controll of new regulatory sequences.
the break that happens during a translocation can disrupt the genes
function
Three Types of Translocation:
Nonreciprocal translocation: genetic material moves from one
chromosome to another without any reciprocal exchange; transfer
ex: ABCDEFG and MNOPQRS ABCDG and
MNOPEFQRS
Reciprocal Translocation: two-way exchange of segments
between the chromosomes
ex: ABCDEFG and MNOPQRS ABCDQRS
and MNOPEFG
Robertsonian Translocation: short arm of one acrocentric
chromosome is exchanged with the long arm of another, creating a large
metacentric chromosome and a fragment chromosome that fails to segregate (is
lost)

Translocation in Meiosis (Dont need to know process in detail, know why gametes are viable
and why some are not)
Non viable gametes
depending on the separation will determine if gametes are viable or not

Translocation in Evolution
During evolution, two ape chromosomes came to form one human chromosome
through robetsonian translocation
this is why humans have 46 instead of 48: weve lost a
homologous pair due to translocation
all the grey spots are homologous areas (DNA similar)

Concept check 3
What is the outcome of a Robertsonian translocation?
One metacentric chromosome and one chromosome with two very short arms
***TQ: Know these examples during a test ***

8.3 Aneuploidy is an Increase or decrease in the number of individual chromsomes

Variations in copy number
Aneuploidy: change in # of individual chromosomes
Polyploidy: change in # of chromosome sets
Causes of Aneuploidy:
deletion of centromere during mitosis and meiosis (-1 in gametes)
spindle fibers have nothign to attach to in a acentric
chromosome, doesnt get pulled to a gamete
result of Robertsonian translocation; the small arm chromosome is
lost (-1 in gametes)
Nondisjunction during meiosis and mitosis (-1 or +1 in gametes)
Nondisjunction: sister chromatids in meiosis or
mitosis or homologous chromosomes in meiosis fail to separate
Nondisjunction can occur at Meiosis 1 and not
Meiosis II or the other way around

Types of Aneuploidy (n=haploid # of chromosomes)

Nullisomy: loss of both members of a homologous pair of
chromosomes (2n-2)
in humans: 44 chromosomes
Monosomy: loss of a single chromsome (2n - 1)
45 chromosomes
Trisomy: gain of a single chromsome (2n + 1)
47 chromosomes
Tetrasomy: gain of both members of a homologous pair (2n + 2)
*not any 2 random chromosomes
48 chromosomes

Concept Check 3
A diploid organism has 2n = 36 chromosomes. How many chromosomes will be found in a
trisomic member of this species?
2n = 36; 36 + 1 = 37
Effects of Aneuploidy
Plants: Jimson weed
can cause different
Each mutant is trisomic for a different chromosome pair

Humans:
Humans have a higher percentage of spontaneous abortion
(miscarriages) and most are due to aneuploidy
In humans, aneuplody happens more often in sex chromosomes
than in autosomes because if you have an extra X chromosome, it will not effect
gene dosage, as it will become a barr body. An extra Y chromsome isnt much of
a problem either because they are small (dont carry a lot of genetic information)
and the genetic information the do carry isnt necessary for viable life.
sex-chromosomes aneuploids
Turner Syndrome: XO (-1 X chromosome)
Klinefelter syndrome: XXY (+1 X chromosome)
Autosomal aneuploids
Trisomy 21: Down syndrome
Chromosome 21 is smaller, so extra
copies of this is not as detrimental is not lethal
increases with mothers birth age
Primary down syndrome: 75%
random nondisjunction in egg formation; extra chromosome 21
non hereditary

Familial Down Syndrome: extra copy

of part of chromosome 21 is attached to another chromosome;
total # of chromosomes is stil 46
same phenotype of
Primary downs, but is hereditary

 Robertsonian
translocation: long arm of 21 and short of 1 change places
producing chromosome with long arms of 14 and 21 and
one chromosome with short arms of 21 and 14, which is
lost.
Translocation Carrier:
(see karyotype w/ blue circles) 45 chromosomes but does
not have down syndrome
receive
d 2 long arms of 14 and 21 from robertsonian
translocation; sufficient amount of DNA to function
properly. The subsequent 14/21 short armed
chromosome, with little DNA, is lost
increas
ed chance of having a child with down syndrome
Affected w/ Familial
Downs: 46 chromosomes; inherited the 14/21 long arm
chromosome, both chromosome 21 and one 14
Translocation Carrier Gametes:
A carrier parent has 1
copy of 21, 1 copy of 14, 1 copy of 14/21
carriers: inherited
14/21 from mom, normal 14 and 21 from dad
normal: inherited 14
and 21 from mom and dad
downs: inherited 21
and 14/21 from mom, and 14 and 21 from dad
lethal: monosomy or
trisomy combinations
Trisomy 18: Edward Syndrome, 1/8000 live bitths
Trisomy 13: Patau syndrome 1/15000 live births
Trisomy 8: 1/25000-1/50000 live births
Why is there a drastic decrease in frequency of
this trisomic syndrome from chromosome 18 to chromosome 8?
Most cases of down syndrome and aneuploy is
caused by maternal disjunction, and the chances of that increases as the
mothers age increases
Uniparental Disomy: both chromosomes are inherited from the
same parent
Starts off as a trisomy, with 2 chromosomes from
one parent and one from the other
If one of the chromosomes is lost, the embryo can
survive (most autosomal trisomies dont); by chance the two remaining
chromosomes may be from one parent resulting in the uniparental disomy
originalte as a trisomy but one chromosome is lost
early in development and the remaining 2 chromosomes are from one
parent

 Mosaicism: type of nondisjunction where patches of tissues have

different chromosome constitutions
8.4 Polyploidy is the Presence of More than Two Sets of Chromosomes
Polyploidy: organism possesses more than two set of chromosomes (triploids-3n,
tetraploids-4n, pentaploid- 5n)
Autopolyploidy: all chromosome sets are from a single species
Allopolyploidy: chromosome sets are from 2 or more species
Autopolypoloidy (via nondisjunction)

Mitosis:
A 2n cell (2n=4) replicates chromsomes (4 chromsomes), they
separate in anaphase (8 chromosomes) but the cell doesnt divide due to
nondisjunction
Product: cell with 8 chromosomes, or 4n
Meiosis
A diploid 2n cell (2n = 4) replicates its chromosomes (4
chromsomes) but undergoes nondisjunction, faling to produce 2 1n gammetes
like meiosis 1 should. It forms 2, 2n gametes with Meiosis II, those gametes
interact wit ha healthy 2n, and form 3n triploid zygotes (autotriploid)
Product:
2 gametes that are 2n like parents fusing with a
normal gamete 1n
producing 3n triploid gamete
Autopolyploids are often sterile

Autotriploid during Meiosis


With normal 2n cells, there 2 chromosomes for a homologous pair align and
separate. But with autotriploids, there are 3 chromosomes that are homologous.
The 3 homologous chromosomes have options in mieosis I:
two chromosomes pair and the other segregates randomly
gamete 1: 2 chromosomes
gamete 2: 1 chromosme
All three pair and all three segregate randomly
gamete 1: 2 chromsomes
gamete 2: 1 chromsome
None pair and all three move to the same cell
Gamete 1: 3 chromsomes
Gamete 2: no chromsomes
NO matter which combination, the result is unbalanced gametes because
numbers of copies of chromsomes varies (2 copies of chromosome 1, 3 copies of
chromsome 2, no copies of chromsome 4)
When these unbalanced gametes fuse with nomormal 2n gametes, the difference
in number creates unbalanced gene dosage that is lethal.
Triploids do not produce viable offspring
Triploid Bananas, watermelons are bred on purpose and are seedless
Allopolyploidy (hybridization between species)

Alloploidy: results from hybridization of two species

The F1 generation hybrid of 1n and 1n gametes (a 2n gamete) is sterile because
if it tried to fuse with a normal gamete, it would contribute unbalanced gametes and they
would die.
The product with ABCGHI is still considered diploid beacuse it
has the same number of chromosomes as the diploid parents.
Parent 1 = 2n, and Parent 2= 2n
F1 is 1n, and F1 is 1n
F1 gametes fuse, and produce a 2n cell, but it is
only diploid because it contains the same amount of chromosomes as the
parent cells, although the chromosmes are not homologous pairs and it is
functionally haploid
However, the F1 hybrid can undergo mitotic
chromosome duplication, doubling the number of each chromsome, and
becoming functionally diploid becasue every chromsome has one and
only one other homologous partner, which is exactly what is needed so

successfully undergo meiosis. it will produce balanced gametes that have

one of each chromosome, and is 1n

The significance of Polyploidy

polyploid cells are physically larger than diploid cells
Plants are polyploids more often the animials
animals are less likely to breed with different
species
Evolution: may give rise to new species

Concept Check 5 (look at worked problem in book)

23.5 Changes in Chromosome Number and STructure are often Associated with Cancer
Chromosomal instability is a general feature of cancer cells
cause by various delations, inversions, translocations
Example: a reciprocal translocation between chromsome 9 and 22
causese chronic myelogenous leukemia
Aneuploidy
Chronic Myelogenous Leukemia
forms ne Philadelphia chromsome that becomes hyperactive
protein; gene overexpression in a position where its not normaly expressed
Burkitt Lymphoma
translocation causes increased proliferation