For medical, nursing, and physiotherapy undergraduates, and postgraduates

1. STRUCTURE OF
CHROMOSOME
DR. SUNDIP CHARMODE
ASSOCIATE PROFESSOR
DEPARTMENT OF ANATOMY
AIIMS RAJKOT

2. INTRODUCTION
• The word chromosome is derived from the Greek
chroma (= color) and soma (= body).
• Under the electron microscope, chromosomes are
seen to have a rounded and rather irregular
morphology.
• Special stains selectively taken up by DNA have
enabled each individual chromosome to be identified.

3. CHROMOSOME MORPHOLOGY
• At cell division, each chromosome can be seen to
consist of two identical strands known as chromatids,
or sister chromatids.
• These sister chromatids can be seen to be joined at a
primary constriction known as the centromere.
• Each centromere divides the chromosome into short
and long arms, designated p (= petite) and q (‘g’ =
grande), respectively.

11. TELOMERE
• The tip of each chromosome arm is known as the
telomere.
• Telomeres play a crucial role in sealing the ends of
chromosomes and maintaining their structural integrity.
• During DNA replication, an enzyme known as
telomerase replaces the 5′ end of the long strand, which
would otherwise become progressively shorter until a
critical length was reached when the cell could no
longer divide and thus became senescent.

12. TELOMERE
• This is in fact part of the normal cellular aging
process, with most cells being unable to undergo
more than 50 to 60 divisions.
• However, in some tumours, increased
telomerase activity has been implicated as a
cause of abnormally prolonged cell survival.

13. CHROMOSOME CLASSIFICATION
• Acrocentric chromosomes sometimes have stalk-like
appendages called satellites that form the nucleolus of
the resting interphase cell and contain multiple repeat
copies of the genes for ribosomal RNA.

14. CHROMOSOME CLASSIFICATION
• Based on the three parameters of length, position of
the centromere, and the presence or absence of
satellites, chromosomes, were subdivided into groups
labelled A to G based on overall morphology:
(A, 1–3; B, 4–5; C, 6–12 X; D, 13–15; E, 16–18;
F, 19–20; G, 21–22 1 Y).

15. CHROMOSOMAL
ABERRATIONS
DR. SUNDIP CHARMODE
ASSOCIATE PROFESSOR
DEPARTMENT OF ANATOMY
AIIMS RAJKOT

16. INTRODUCTION
• Numerical aberrations
• Structural aberrations

17. NUMERICAL ABERRATIONS

18. ANEUPLOIDY
• However, if one or more chromosomes (not an
entire set) are missing, or are present in
excess, then the cell would be considered to
represent a state called aneuploidy.
• Aneuploid cells do not contain multiples of
the haploid number of chromosomes.

19. EUPLOIDY
• Euploidy is a condition when a cell or an
organism has one or more than one complete
set of chromosomes.

20. MONOSOMY
• Loss of single chromosome
• Monosomy of autosomes is lethal
• Turners syndrome
• Cause : Disjunction

21. TRISOMY
• Gain of homologous chromosome
• Trisomy 21
• Trisomy 18
• Trisomy 13
• Klienfelters syndrome

26. NON-DISJUNCTION
• Unequal distribution of chromosomes in
daughter cells.
• Instead of a member of homologous
chromosome pair, the pair goes to one
daughter cell and the other daughter cell is
devoid of this chromosome.

28. THE ORIGIN OF NON-DISJUNCTION
• The consequences of non-disjunction in meiosis I and meiosis
II differ in the chromosomes found in the gamete.
• An error in meiosis I leads to the gamete containing both
homologs of one chromosome pair.
• In contrast, non-disjunction in meiosis II results in the gamete
receiving two copies of one of the homologs of the
chromosome pair.
• Studies using DNA markers have shown that most children
with an autosomal trisomy have inherited their additional
chromosome as a result of nondisjunction occurring during
one of the maternal meiotic divisions (Table 3.4).

29. THE ORIGIN OF NON-DISJUNCTION
• Non-disjunction can also occur during an early
mitotic division in the developing zygote.
• This results in the presence of two or more different
cell lines, a phenomenon known as mosaicism.

31. THE CAUSE OF NON-DISJUNCTION
• The cause of non-disjunction is uncertain.
• The most favoured explanation is that of an aging
effect on the primary oocyte, which can remain in
a state of suspended inactivity for up to 50 years
(p. 32).
• This is based on the well-documented association
between advancing maternal age and increased
incidence of Down syndrome in offspring (see
Table 17.4; see p. 237).
• A maternal age effect has also been noted for
trisomies 13 and 18.

32. THE CAUSE OF NON-DISJUNCTION
• It is not known how or why advancing maternal
age predisposes to non-disjunction, although
research has shown that absence of
recombination in prophase of meiosis I
predisposes to subsequent non-disjunction.
• This is not surprising, as the chiasmata that are
formed after recombination are responsible for
holding each pair of homologous chromosomes
together until subsequent separation occurs in
diakinesis.

33. THE CAUSE OF NON-DISJUNCTION
• Thus, failure of chiasmata formation could allow
each pair of homologs to separate prematurely
and then segregate randomly to daughter cells.

34. POLYPLOIDY
• Multiples of haploid number
• Triploidy / tetraploidy
• Foetus does not survive.
• Causes :
1. Retention of polar body
2. Formation of diploid sperm
3. Dispermy – fertilization by 2 sperms

38. STRUCTURAL ABERRATIONS
• Structural rearrangements in chromosomes
essentially result from breaks followed by
reconstitution.
• The factors responsible are :
1. Ionizing radiation
2. Chemical agents
3. Viruses

39. STRUCTURAL ABERRATIONS
• Stable : e.g., deletions, inversions, translocations,
isochromosomes.
• Unstable : e.g., dicentric, ring chromosomes

40. DELETION
• This involve loss of a part of chromosome. It is of
two types :
• Terminal deletion
• Interstitial deletion

41. TERMINAL DELETION
• It involves a single break, and the terminal part of
the chromosome is lost.
• Spontaneously or may be induced by radiation ,
uv, chemicals, viruses.
• First observed by Bridges in 1917 in Drosophila.
• E.g. Crid du chat syndrome

42. CRID DU CHAT SYNDROME
• This results from deletion of the short arm of
chromosome 5.
• It is called so as the cry of baby mimics mewing of
a cat.
• Typical facial appearance, Microcephaly,
Hypertelorism and anti-mongoloid slant of
palpebral fissures, low set ears and Micrognathia.

45. INTERSTITIAL DELETION
• It involves two breaks and the intervening portion
of the chromosome is lost / Loss of segment in
between centromere and telomere.
• E.g. Prader willi syndrome, Wilms tumour with
aniridia called as Micro-deletion syndromes.
• Effects of Deletion :
• Crossing over does not occur
• Harmful effects on Diploid organisms
• Morphological effects

46. PRADER WILLI SYNDROME
• There is deletion of 3-4 mbp of chromosome 15.
• Inherited from father
• Short stature, Hypotonia, obesity, small hands
and feet, mild to moderate Mental retardation,
Hypogonadism, Hyperphagia, failure to thrive.

49. ANGELMAN SYNDROME
• There is deletion of 3-4 mbp of chromosome 15.
• Inherited from Mother.
• Developmental delay, absent speech, severe
mental retardation, seizures and ataxia gait.

52. GENOMIC IMPRINTING
• It refers to differential activation of genes
depending upon the parent from whom they
are inherited.
• The portion of chromosome 15 involved in
both the syndromes is referred to as ‘Critical
region’.

53. GENOMIC IMPRINTING
• In the critical region of chromosome 15,
several genes are transcriptionally active only
on chromosome inherited from father and
they are inactive on the chromosomes
inherited from mother.
• Similarly, other genes in this region are
transcriptionally active only on chromosome
inherited from mother and they are inactive
on the chromosomes inherited from father.

54. GENOMIC IMPRINTING
• With High Resolution Banding, it is now
possible to identify the number of such
deletions.
• FISH techniques made possible to detect
micro-deletions.(< 5mb)
• In 50 % cases, the actual locus is 15q, 11-13

55. MICRO-DELETION SYNDROMES
1. Angelman syndrome
2. Prader Willi syndrome
3. Miller Dieker syndrome
4. Wilms tumour with aniridia
5. Rubinstein Taybi syndrome
6. Langer Giedion syndrome
7. Smith Magenis syndrome

56. TRANSLOCATION
• There are two types :
1. Robertsonian translocation
2. Reciprocal translocation

57. ROBERTSONIAN TRANSLOCATION
• This involves only Acrocentric chromosomes.
• E.g., D /G group chromosomes - 13,14,15,21,22.
• Incidence is 1 in 1000
• The short arm of D group chromosome fuses with
short arm of G group chromosome.
• The fragment formed by their fusion is lost.
• This process is called ‘Centric fusion’.
• P arm contains repeated information.

58. ROBERTSONIAN TRANSLOCATION
• Fusion of long arms to form one chromosome.
• Total chromosome number is reduced to 45.
• Robertsonian translocation carriers are normal.
• But can produce unbalanced gametes resulting in
monosomic or trisomic zygotes
• Commonest example : Chromosome 13 and 14.

59. ROBERTSONIAN TRANSLOCATION
• Most important clinical effect of Robertsonian
translocation arises from those involving
chromosome 21.
• Translocation involving chromosome 22 are rare.
• Robertsonian translocation found in 4 % of Down
syndrome cases. Recurrence is common.
• Remaining cases of Downs are due to Non-
disjunction with no familial recurrence.

62. ROBERTSONIAN TRANSLOCATION
• Balanced translocation:
–When the exchange results in no loss or gain of
DNA.
–Individual is clinically normal
• Unbalanced translocation:
–Chromosomal deletion /addition

63. RECIPROCAL TRANSLOCATION
• Exchange of chromosome material distal to
breaks.
• It involves non-homologous chromosomes.
• This amounts to balanced translocation and no
material is lost.
• This amounts to production of abnormal gametes
– presenting unbalanced chromosomal
complement – spontaneous abortions / child
with congenital anomaly.

65. INSERTION
• It is a rare non-reciprocal type of translocation
that involves three breaks.
• Two breaks release the fragment from one
chromosome and one break occurs in another
chromosome to admit this fragment.

67. INVERTION
1. Peri-centric inversion
2. Para-centric inversion
• It involve two breaks along the chromosome.
• In Peri-centric inversion – both p and q are
involved
• In Para-centric inversion – only one arm p or q is
involved.
• It does not give rise to abnormal phenotype in
the individual.

69. ISO-CHROMOSOME
• This involves split along the centromere leading
to separation of arms.
• E.g. Turners syndrome

72. RING CHROMOSOME
• This involves two breaks at the terminal portions
of the chromosome followed by fusion of the cut
ends.
• 1/5th cases of Turner syndrome.

74. FACTORS PLAYING ROLE IN
CHROMOSOMAL ABERRATIONS
1. Maternal age
2. Non-disjunction gene
3. Radiation
4. Chromosomal abnormality
5. Autoimmune disorders

75. THANK YOU