2. Introduction
• Chromosome mutations have proved to be of great significance in applied biology
agriculture (including horticulture), animal husbandry and medicine.
• Chromosome mutations are inherited once they occur and are of the following types :
• A. Structural changes in chromosomes :
• 1. Changes in number of genes
• (a) Loss : deletion
• (b) Addition : Duplication
• 2. Changes in gene arrangement :
• (a) Rotation of a group of genes 1800 within one chromosome : inversion
• (b) Exchange of parts between chromosomes of different pairs : translocation.
• B. Changes in number of chromosomes :
• 1. Loss, or gain, of a part of the chromosome set (aneuploidy)
• 2. Loss, or gain, of whole chromosome set (euploidy)
• (a) Loss of an entire set of chromosomes (haploidy)
• (b) Addition of one or more sets of chromosomes (polyploidy)
3. STRUCTURAL CHANGES IN CHROMOSOMES
• For better understanding of the abnormalities of chromosome
structure, let us consider two important features of chromosome
behaviour :
• (1) During prophase I of meiosis, homologous regions of
chromosomes show a great affinity for pairing and they often go
through considerable contortions in order to pair. This property
results in many curious structures observed in cells containing one
normal chromosome set plus an aberrant set.
• (2) structural changes usually involve chromosome breakage; the
broken chromosome ends are highly “reactive” or “sticky”, showing
strong tendency to join with broken ends.
4. Types of Structural Changes in Chromosome
• Structural changes in chromosome may be of the following types (Fig. 14.1)
:
• 1. deficiency or deletion which involves loss of a broken part of a
chromosome;
• 2. duplication involves addition of a part of chromosome (i.e., broken
segment becomes attached to a homolog which, thus, bears one block of
genes in duplicate);
• 3. inversion in which broken segment reattached to original chromosome
in reverse order, and
• 4. translocation in which the broken segment becomes attached to a non
homologous chromosome resulting in new linkage relations.
5. • Further, structural abnormalities can occur in both homologous
chromosomes of a pair or in only one of them.
• When both homologous chromosomes are involved, these are called
structural homozygotes, e.g., deletion homozygote, duplication
homozygote, etc.
• When only one homologous chromosome is involved, it is called
structural heterozygote.
6. 1. Deletion (or Deficiency)
• The simplest result of breakage is the loss of a part of a chromosome.
Portions of chromosomes without a centromere (called acentric fragments)
lag in anaphase movement and are lost from reorganizing nuclei or
digested by nucleases. Such loss of a portion of a chromosome (and of
some genes) is called deletion.
• The chromosomes with deletions can never revert to a normal condition.
• If gametes arise from the cells having a deleted chromosome, this deletion
is transmitted to the next generation. Further, a deletion can be terminal
or intercalary (interstitial).
• In terminal deletion a terminal section of a chromosome is absent and it is
resulted by only one break (Fig. 14.3).
7. • While in the intercalary deletion, an intermediate section or portion
of chromosome is lost and it is caused by two breaks —one on either
end of the deleted region (Fig. 14.3).
• Thus, in the latter case, the chromosome is broken into three pieces,
the middle one of which is lost and the remaining two pieces get
joined again
8.
9. • In general, if a homozygous deletion is made, it is lethal.
• Even individuals heterozygous for deletion (deletion in one of the
homologous chromosomes) may not survive.
• However, smaller deletion in heterozygous condition can be tolerated
by the organisms.
• If meiotic chromosomes in such heterozygotes are examined, the
region of deletion can be detected by the failure of the corresponding
segment on the normal chromosome to pair properly; so a “deletion-
loop” results.
10. • Deletion loops are also detected in polytene chromosomes of
Drosophila, where the homologs exist in permanent state of pairing
(Fig. 14.4).
• The cytological studies of pairing between normal and deleted
chromosomes have helped a lot in finding out the relative positions of
genes in chromosomes.
11.
12. • Genetical effects of deletion.
• Deletion of some chromosome regions produce their own unique
phenotypes. A good example of this is a dominant notch-wing
mutation in Drosophila.
• In fact, this is a small deletion and acts as a recessive lethal in this
regard.
• Further, in the presence of a deletion, a recessive allele of the normal
homologous chromosome will behave like a dominant allele, i.e., it
will be phenotypically expressed, this phenomenon is called
pseudodominance (Fig. 14.5).
13. • The phenomenon of pseudodominance exhibited by deficiency
heterozygotes has been utilized for the location of genes on specific
chromosomes and in preparing cytological maps in Drosophila, maize,
bacteriophage and other organisms.
• Such cytological maps are often used to verify the genetic maps
(based on linkage analysis) of these organisms
14.
15. • Examples of pseudodominance (deletion).
• 1. Gates (1921) demonstrated the effects of pseudodominance.
Certain mice carrying the recessive allele (v) in homozygous condition
move about erratically until exhausted.
• Such mice are called ‘waltzing mice’. When homozygous waltzing
mice (vv) are mated with normal mice carrying the dominant allele
(VV), all the affecting (Vv) are normal.
• However, in a cross between homozygous normal female and a
waltzer male, one of the seven offspring was a waltzer.
• A deletion had resulted in the elimination of the dominant allele (V);
so that the recessive allele (v) for waltzing had expressed itself.
16. • 2. Human babies missing a portion of the short arm of chromosome 5
(autosome) have a distinctive cat-like cry; hence, the French name
“cri du chat” (cry of the cat) syndrome.
• They are also mentally retarded (IQ below 20), have malformation in
the larynx, moon faces, saddle noses, small mandibles (micrognathia),
malformed low-set ears and microcephally (small head).
• The standard designation for the short arm of a non-metacentric
chromosome is p, that for the longer arm is q. A deletion is indicated
by a superscript minus sign, and added segments are indicated by
supercript plus sign. Hence, the karyotype of a cri du chat patient is
5p–.
17. 2. Duplication
• The presence of a part of a chromosome in excess of the normal
complement is known as duplication.
• Thus, due to duplication some genes are present in a cell in more
than two doses.
• If duplication is present only on one of two homologous
chromosomes, at meiosis the chromosome bearing the duplicated
segment forms a loop to maximize the juxtaposition (during pairing)
of homologous regions (Fig. 14.7).
18.
19. Types of Duplication
• Extra segments in a chromosome may arise in a variety of ways such
as follows :
• 1. Tandem duplication. In this case the duplicated region is situated
just by the side of the normal corresponding section of the
chromosome and the sequences of genes are the same in normal and
duplicated region.
• For example, if the sequence of genes in a chromosome is ABC.
DEFGH (The full stop depicts the centromere) and if the chromosomal
segment containing the genes DEF is duplicated, the sequence of
genes in tandem duplication will be ABC. DEF .DEF.GH.
20. • 2. Reverse tandem duplication. Here, the sequence of genes in the
duplicated region of a chromosome is just the reverse of a normal
sequence. In the above mentioned example, therefore, the sequence
of genes due to reverse tandem duplication will be ABC. DEF.EFD.GH.
• 3. Displaced duplication. In this case the duplicated region is not
situated adjacent to the normal section. Depending on whether the
duplicated portion is on the same side of the centromere as the
original section or on the other side, the displaced duplication can be
termed either homobranchial or heterobranchial.
• Example. Homobranchial duplication = ABC. DEFG .DEF.H
Heterobranchial duplication = A DEFB C. DEFGH
21. • 4. Transposed duplication. Here, the duplicated portion of
chromosome becomes attached to a non-homologous chromosome.
• For example, if ABC.DEFGH and LMNOPQ. RST represent the gene
sequences of two non homologous chromosomes, a transposed
duplication will result into chromosomes with gene sequence ABC.GH
and LMN .DEF OPQ. RST. Such a transposed duplication may be either
interstitial (e.g., LMN .DEF OPQ. RST) or terminal (i.e., LMN OPQ. RST
DEF. ).
• 5. Extra-chromosomal duplication. In the presence of centromere the
duplicated part of a chromosome act as independent chromosome.
22. Genetical effects of duplication.
• Due to duplication, there occur unequal crossing over which results in deletion
and reduplication which produce distinct phenotypes as shown by the following
examples :
• 1. Bar eye in Drosophila.
• The Bar phenotype of Drosophila is characterized by narrower, oblong, bar-
shaped eye with few facets. It is determined by a X-linked recessive allele B.
• The classical studies of Bridges (1936) showed that the bar trait of Drosophila is
associated with the duplication of a segment of the X-chromosome, called
section 16A, as observed in salivary gland chromosomes.
• Each added section 16A intensifies the bar phenotype (i.e., duplication behaves
genetically as a dominant factor).
• However, the narrowing effect is greater if the duplicated segments are on the
same chromosome (called position effect) (Table 14-1).
23. • 2. In humans, unequal crossing over between homologous
chromosomes bearing σ (sigma) and β (beta) genes for σ and β
subunits of adult haemoglobin (HbA), results in deletions and
duplications of these genes.
• Deletions result in Lepore and Kenya variants of adult haemoglobin
(HbA), both causing anaemia (i.e., one type of thalassemia), while
duplication result in Anti-Lepore and AntiKenya variants of
haemoglobin A.
• Genetic redundancy, of which duplication is one type, may protect
the organism from the effects of a deleterious recessive gene or from
an otherwise lethal deletion.
24. • Thus, cis and trans arrangements of the same number of 16A
segments give different phenotypes (compare heterozygous ultrabar
and homozygous bar eyes).
• Some of the other well known duplications of Drosophila lead to
following phenotypic effects :
• (1) a reverse repeat in chromosome 4 causes eyeless dominant (Ey);
• (2) a tandem duplication in chromosome 3 causes confluens (Co)
resulting in thickened veins, and
• (3) another duplication causes hairy wing (Hw).
25. 3. Inversion Inversion
• Involves a rotation of a part of a chromosome or a set of genes by
180° on its own axis. It essentially involves occurrence of breakage
and reunion.
• The net result of inversion is neither a gain nor a loss in the genetic
material but simply a rearrangement of the gene sequence.
• An inversion can occur in the following way : suppose that the normal
order of segments within a chromosome is 1-2- 3-4-5-6 ; breaks occur
in regions 2-3 and 5-6 and broken piece is reinserted in reverse order.
• This results in an inverted chromosome having segments 1-2-5-4-3-6
26. • An inversion heterozygote has one chromosome in the inverted order and its
homologue in the normal order.
• The location of the inverted segment can be detected cytologically in the meiotic
nuclei of such heterozygotes by the presence of an inversion loop in the paired
homologs.
• The location of the centromere relative to inverted segment determines the
genetic behaviour of the chromosomes.
• If the centromere is not included in the inversion it is called paracentric inversion
and when inversion includes the centromere it is called pericentric inversion (Fig.
14.9).
• Homologous chromosomes, with identical inversions in each member, pair and
undergo normal distribution in meiosis. However, crossing over in inversion
heterozygotes produce deletions, duplications and other curious configurations.
27. • A. Crossing over in pericentric inversion.
• Crossing over in a heterozygous pericentric inversion result in deletions and
duplications and also produces rod-shaped (acrocentric) chromosomes.
• The first meiotic anaphase figures appear normal, but the two chromatids
of each chromosome usually have arms of unequal length depending upon
where the crossing over occurred (Fig. 14.10).
• Half of the meiotic products (gametes/pollen grains) are non-functional
and inviable due to the presence of duplications and deletions in them.
• The other half of the gametes are functional : one-quarter have the normal
chromosome order, one-quarter have the inverted arrangement.
28. • B. Crossing over in paracentric inversion.
• A crossing over in the inverted region of a heterozygous paracentric
inversion produces a dicentric chromosome (possessing two centromeres)
which forms a bridge from one pole to the other during first anaphase.
• The bridge will rupture somewhere along its length and resulting fragments
will contain duplication and/or deletion. In this case, an accentric fragment
(without a centromere) is also formed and since it usually fails to move to
either pole, it is not included in any meiotic products (gametes).
• Here also half of the meiotic products are nonfunctional, one-quarter are
functional with a normal chromosome, and one-quarter are functional
with an inverted chromosome (Fig. 14.11).
• Thus, heterozygotes for paracentric inversions are highly sterile and
produce only parent-like progeny.
29.
30.
31. 4. Translocation
• The shifting or transfer of a part of a chromosome or a set of genes to a
non-homologous one, is called translocation.
• There is no addition or loss of genes during translocations, only a
rearrangement (i.e., change in the sequence and position of a gene).
Translocations may be of following three types (Fig. 14.12) :
• 1. Simple translocations. They involve a single break in a chromosome. The
broken piece gets attached to one end of a nonhomologous chromosome.
• 2. Shift translocation. In this type of translocation, the broken segment of
one chromosome gets inserted interstitially in a nonhomologous
chromosome.
• 3. Reciprocal translocations. In this case, a segment from one chromosome
is exchanged with a segment from another nonhomologous one, so that in
reality two translocation chromosomes are simultaneously achieved.
32. • Outcomes of reciprocal translocation.
• The exchange of chromosome parts between nonhomologous
chromosomes creates new linkage relationships.
• Such translocations also drastically change the size of a chromosome
as well as the position of its centromere.
• For example, a large metacentric chromosome is shortened by one-
half in length to an acrocentric one, where as the small chromosome
becomes a large one.
33. • Translocation complexes and lethality.
• In Oenothera, a rare series of reciprocal translocations have occurred
which involve all 7 of its chromosome pairs.
• If each chromosome end is labelled with a different number, the
normal set of 7 chromosomes would be represented as 1-2, 3-4, 5-6,
7-8, 9-10, 11-12, and 13-14; likewise a translocation set would be
represented as 2-3, 4-5, 6-7, 8-9, 10-11, 12-13 and 14-1.
34. • Such a multiple translocation heterozygotes would form a ring of 14
chromosomes during meiosis. Different lethals in each of two haploid
sets of 7 chromosomes administer structural heterozygosity.
• Since only alternate disjunction from the ring can form viable
gametes, each group of 7 chromosomes behaves as though it were a
single large linkage group with recombination confined to the pairing
ends of each chromosome.
• Each set of chromosomes which is inherited as a single unit is called a
“Renner complex.”
35. Variation in Chromosome Morphology
• Various changes in chromosome structure often produce variation in
chromosome morphology such as isochromosomes, ring
chromosomes and Robertsonian translocation.
• 1. Isochromosomes.
• An isochromosome is a chromosome in which both arms are
identical. It is thought to arise when a centromere divides in the
wrong plane, yielding two daughter chromosomes, each of which
carries the information of one arm only but present twice.
• For example, telocentric X chromosome of Drosophila may be
changed into an “attached-X” which is formed due to misdivision of
the centromere (Fig. 14.20).
36.
37. • 2. Ring chromosomes.
• Chromosomes are not always rod-shaped. Occasionally ring
chromosomes are encountered in higher organisms. Sometimes
breaks occur at each end of the chromosome and broken ends are
joined to form a ring chromosome.
• Crossing over between ring chromosomes can lead to bizarre
anaphase figures (Fig. 14.21).
38.
39. • 3. Robertsonian translocation.
• Sometimes whole arm fusions occur in the non-homologous
chromosomes. It is called Robertsonian translocation. Thus, Robertsonian
translocation is an eucentric reciprocal translocation where the break in
one chromosome is near the front of the centromere and the break in the
other chromosomes is immediately behind its centromere.
• The resultant smaller chromosome consists of largely inert
heterochromatic material near the centromere; it normally contains no
essential genes and tends to become lost.
• Thus, Robertsonian translocation results in a reduction of the chromosome
number (Fig. 14.22).
