Chromosomes

variations

Dr. Asad Ilyas

• Variations in the number and structure of
chromosomes are termed chromosome mutations
• Chromosome mutations can be grouped into three basic categories:
chromosome rearrangements, aneuploidy, and polyploidy

• Chromosome rearrangements alter the structure of chromosomes;

for example, a piece of a chromosome may be duplicated, deleted, or
inverted
• In aneuploidy, the number of chromosomes is altered: one or more
individual chromosomes are added or deleted.

• In polyploidy, one or more complete sets of chromosomes are added.

A polyploidy is any organism that has more than two sets of
chromosomes (3n, 4n, 5n, or more).
Chromosome Rearrangements
• Chromosome rearrangements are mutations that change the
structure of individual chromosomes.

• The four basic types of rearrangements are duplications, deletions,

inversions, and translocations
 Duplications
• A chromosome duplication is a mutation in which part of the
chromosome has been doubled

• This type of duplication, in which the duplicated segment is immediately

adjacent to the original segment, is called a tandem duplication.
• If the duplicated segment is located some distance from the original
segment, either on the same chromosome or on a different one, the
chromosome rearrangement is called a displaced duplication

• A duplication can be either in the same orientation as that of the

original sequence, as in the two preceding examples, or inverted:
AB•CDEFFEG. When the duplication is inverted, it is called a reverse
duplication.
• An individual that is homozygous for a duplication carries that
duplication on both homologous chromosomes, and an individual
that is heterozygous for a duplication has one normal chromosome
and one chromosome with the duplication.
• In heterozygotes, problems in
chromosome pairing arise at prophase I
of meiosis because the two
chromosomes are not homologous
throughout their length.
• The pairing and synapsis of homologous
regions require that one or both
chromosomes loop and twist so that
these regions are able to line up
• The appearance of this characteristic
loop structure in meiosis is one way to
detect duplications.
Deletions
• A second type of chromosome rearrangement is a chromosome
deletion, the loss of a chromosome segment
A chromosome with segments
AB•CDEFG that
undergoes a deletion of segment
EF would generate the mutated
chromosome AB•CDG.
• The phenotypic consequences of a deletion depend on which genes are
located in the deleted region.

• If the deletion includes the centromere, the chromosome will not

segregate in meiosis or mitosis and will usually be lost.

• Many deletions are lethal in the homozygous state because all copies of
any essential genes located in the deleted region are missing
• Even individuals heterozygous for a deletion may have multiple defects,
for three reasons.
• First, the heterozygous condition may produce imbalances in the
amounts of gene products, similar to the imbalances produced by extra
gene copies.
• Second, normally recessive mutations on the homologous chromosome
lacking the deletion may be expressed when the wild-type allele has
been deleted (and is no longer present to mask the recessive allele’s
expression).
• The expression of a normally recessive mutation is referred to as
pseudodominance, and it is an indication that one of the homologous
chromosomes has a deletion.

• Third, some genes must be present in two copies for normal function.
• When a single copy of a gene is not sufficient to produce a wild-type
phenotype, it is said to be a haplo insufficient gene.
Inversions
• A third type of chromosome rearrangement is a chromosome
inversion, in which a chromosome segment is inverted— turned 180
degrees
• If a chromosome originally had segments AB•CDEFG, then
chromosome AB•CFEDG represents an inversion that includes
segments DEF.
• For an inversion to take place, the chromosome must break in two
places.
• Inversions that do not include the centromere, such as AB•CFEDG,
are termed paracentric inversions

• whereas inversions that include the centromere, such as ADC•BEFG,

are termed pericentric inversions
• Individual organisms with inversions have neither lost nor gained any
genetic material; only the order of the chromosome segment has been
altered.

• Nevertheless, these mutations often have pronounced phenotypic

effects. An inversion may break a gene into two parts, and one part may
move to a new location and destroy the function of the gene in that
location.

• Even when the chromosome breaks lie between genes, phenotypic

effects may arise from the inverted gene order
Translocations
• A translocation entails the movement of genetic material between
nonhomologous chromosomes or within the same chromosome.
• In a nonreciprocal translocation, genetic material moves from one
chromosome to another without any reciprocal exchange. Consider the
following two nonhomologous chromosomes: AB•CDEFG and
MN•OPQRS.

• If chromosome segment EF moves from the first chromosome to the

second without any transfer of segments from the second chromosome
to the first, a nonreciprocal translocation has taken place, producing
chromosomes AB•CDG and MN•OPEFQRS.
• More commonly, there is a two-way exchange of segments between the
chromosomes, resulting in a reciprocal translocation. A reciprocal
translocation between chromosomes AB•CDEFG and MN•OPQRS might
give rise to chromosomes AB•CDQRS and MN•OPEFG.
• Translocations can affect a phenotype in several ways.

• First, they can physically link genes that were formerly located on
different chromosomes.

• These new linkage relations may affect gene expression: genes

translocated to new locations may come under the control of different
regulatory sequences or other genes that affect their expression.

• Second, the chromosome breaks that bring about translocations may

take place within a gene and disrupt its function.
• Deletions frequently accompany translocations. In a Robertsonian
translocation, for example, the long arms of two acrocentric
chromosomes become joined to a common centromere through a
translocation, generating a metacentric chromosome with two long
arms and another chromosome with two very short arms
Aneuploidy
• Variations in chromosome number can be classified into two basic
types:

• aneuploidy, which is a change in the number of individual

chromosomes
• polyploidy, which is an increase in the number of chromosome sets.
• Aneuploidy can arise in several ways.
• First, a chromosome may be lost in the course of mitosis or meiosis if, for
example, its centromere is deleted.
• Loss of the centromere prevents the spindle microtubules from attaching, so
the chromosome fails to move to the spindle pole and does not become
incorporated into a nucleus after cell division.

• Second, the small chromosome generated by a Robertsonian translocation

may be lost in mitosis or meiosis.

• Third, aneuploidy may arise through nondisjunction, the failure of

homologous chromosomes or sister chromatids to separate in meiosis or
mitosis.
• Nondisjunction leads to some gametes or cells that contain
an extra chromosome and other gametes or cells that are
missing a chromosome
Types of Aneuploidy
• Nullisomy is the loss of both members of a homologous pair of
chromosomes.
• It is represented as 2n - 2, where n refers to the haploid number of
chromosomes.
• Thus, among humans, who normally possess 2n = 46 chromosomes, a
nullisomic zygote has 44 chromosomes.
• Monosomy is the loss of a single chromosome, represented as 2n - 1.
A human monosomic zygote has 45 chromosomes.
• Trisomy is the gain of a single chromosome, represented as 2n + 1.

• A human trisomic zygote has 47 chromosomes.

• The gain of a chromosome means that there are three homologous
copies of one chromosome
• Tetrasomy is the gain of two homologous chromosomes, represented
as 2n + 2.
• A human tetrasomic zygote has 48 chromosomes.

• Tetrasomy is not the gain of any two extra chromosomes, but rather
the gain of two homologous chromosomes, so that there are four
homologous copies of a particular chromosome.
• Aneuploidy usually alters the phenotype drastically.
• In most animals and many plants, aneuploid mutations are lethal.
• Because aneuploidy affects the number of gene copies, but not their
nucleotide sequences, the effects of aneuploidy are most likely due to
abnormal gene dosage.
• Aneuploidy alters the dosage for some, but not all, genes, disrupting
the relative concentrations of gene products and often interfering
with normal development.
DOWN SYNDROME,
Trisomy 21
• Down syndrome, also known as trisomy 21, is
the most common autosomal aneuploidy in
humans
• intellectually disabled patients: all of them
possessed a broad, flat face, a small nose, and
oval-shaped eyes

• worldwide incidence is about 1 in 700 human

births
• Appriximately 92% of Down syndrome cases have Three full copies of
chromosome 21 (and therefore a total of 47 chromosomes), a
condition termed primary Down syndrome

• Primary Down syndrome usually arises from spontaneous

nondisjunction in egg formation: about 75% of the nondisjunction
events that cause Down syndrome are maternal in origin, most arising
in meiosis I.
• Most children with Down syndrome are born to normal parents, and
the failure of the chromosomes to divide has little hereditary
tendency.
• A couple who has conceived one child with primary Down syndrome
has only a slightly higher risk of conceiving a second child with Down
syndrome.
• Similarly, the couple’s relatives are not more likely to have a child with
primary Down syndrome
• About 4% of people with Down syndrome are not trisomic for a
complete chromosome 21.
• Instead, they have 46 chromosomes, but an extra copy of part of
chromosome 21 is attached to another chromosome through a
translocation.
• This condition is termed familial Down syndrome because it has a
tendency to run in families. The phenotypic characteristics of familial
Down syndrome are the same as those of primary Down syndrome
• Trisomy 18, also known as Edward syndrome, arises with a frequency
of approximately 1 in 8000 live births.
• Babies with Edward syndrome have severe intellectual disability, low-
set ears, a short neck, deformed feet, clenched fingers, heart
problems, and other disabilities.
• Few live for more than a year after birth. Trisomy 13 has a frequency
of about 1 in 15,000 live births and produces features that are
collectively known as Patau syndrome
• Characteristics of this condition include severe intellectual disability, a
small head, sloping forehead, small eyes, cleft lip and palate, extra
fingers and toes, and numerous other problems.

• About half of children with trisomy 13 die within the first month of
life, and 95% die by the age of 3.
• Rarer still is trisomy 8, which arises with a frequency ranging from
about 1 in 25,000 to 1 in 50,000 live births.
• This aneuploidy is characterized by intellectual disability, contracted
fingers and toes, low-set malformed ears, and a prominent forehead.

• Many people who have this condition have a normal life expectancy.
Polyploidy
• Polyploidy is an increase in the number of chromosome sets.
• Polyploids include triploids (3n), tetraploids (4n), pentaploids (5n),
and even higher numbers of chromosome sets.
• Polyploidy is common in plants and is a major mechanism by which
new plant species have evolved.

• Polyploidy is less common in animals but is found in some

invertebrates, fishes, salamanders, frogs, and lizards.

• No naturally occurring, viable polyploids are known in birds and

mammals
Autopolyploidy
• Autopolyploidy is caused by accidents of mitosis or meiosis that
produce extra sets of chromosomes, all derived from a single species

• Nondisjunction of all chromosomes in mitosis in an early 2n embryo,

for example, doubles the chromosome number and produces an
autotetraploid (4n),
• An autotriploid (3n) may arise when nondisjunction in meiosis
produces a diploid gamete that then fuses with a normal haploid
gamete to produce a triploid zygote

• Nondisjunction can be artificially induced by chemicals that disrupts

spindle formation. Colchicine is often used to induce polyploidy in
agriculturally and ornamentally important plants.
Allopolyploidy
• Allopolyploidy arises from hybridization between two species; the
resulting polyploid carries chromosome sets derived from two or
more species.
• Species 1 (AABBCC, 2n = 6) produces
haploid gametes with chromosomes
ABC,
• and species 2 (GGHHII, 2n = 6) produces
haploid gametes with chromosomes GHI
If gametes from species 1 and 2 fuse, a
hybrid with six chromosomes (ABCGHI) is
created

• The hybrid has the same chromosome

number as that of both diploid species,
so the hybrid is considered diploid
• However, because the hybrid
chromosomes are not homologous, they
will not pair and segregate properly in
meiosis; this hybrid is functionally
haploid and sterile

• The sterile hybrid is unable to produce

viable gametes through meiosis, but it
may be able to perpetuate itself
t0hrough mitosis (asexual reproduction)
• On rare occasions, nondisjunction takes place in a
mitotic division, which leads to a doubling of
chromosome number and an allotetraploid with
chromosomes AABBCCGGHHII.

• This type of allopolyploid, consisting of two

combined diploid genomes, is sometimes called an
amphidiploid
• Although the chromosome number has doubled
compared with what was present in each of the
parental species,
• the amphidiploid is functionally diploid: every
chromosome has one and only one homologous
partner, which is exactly what meiosis requires for
proper segregation.

• The amphidiploid can now undergo normal

meiosis to produce balanced gametes with six
chromosomes each.