CHROMOSOME STRUCTURE,

VARIATION AND
ABNORMALITIES.

samridhi singh
BSC .MICROBIOLOGY  sem4th
INTRODUCTION

German biologist Walter Flemming in the early 1880s revealed that

during cell division the nuclear material organize themselves into
visible thread like structures which were named as chromosomes
which stains deep with basic dyes. The term chromosome was
coined by W. Waldeyer in 1888. Chrome is coloured and soma is
body, hence they mean “colored bodies” and can be defined as
higher order organized arrangement of DNA and proteins. It contains
many genes or the hereditary units, regulatory elements and other
nucleotide sequences. Chromosomes also contain DNA-bound
proteins, which serve in packaging the DNA and control its functions.
Chromosomes vary both in number and structure among organisms
and the number of chromosomes is characteristic of every species.
Benden and Bovery in 1887 reported that the number of
chromosomes in each species is constant. W.S. Sutton and T. Boveri
in 1902 suggested that chromosomes are the physical structures
which acted as messengers of heredity.
Chromosomes are tightly coiled DNA around basic histone proteins,
which help in the tight packing of DNA. During interphase, the DNA is
not tightly coiled into chromosomes, but exists as chromatin. The
structure of a chromosome. In eukaryotes to fit the entire length of
DNA in the nucleus it undergoes condensation and the degree to
which DNA is condensed is expressed as its packing ratio which is the
length of DNA divided by the length into which it is packaged into
chromatin along with proteins.
Figure 2: Eukaryotic chromosome

The shortest human chromosome contains 4.6 x 107 bp of DNA. This

is equivalent to 14,000 µm of extended DNA. In its most condensed
state during mitosis, the chromosome is about 2 µm long. This gives
a packing ratio of 7000 (14,000/2). The DNA is packaged stepwise
into the higher order chromatin structure and this is known as
“hierarchies of chromosomal organization”. The level of DNA
packaging is schematically represented in Table 2.
Chromosome number:
There are normally two copies of each chromosome present in every
somatic cell. The number of unique chromosomes (N) in such a cell is
known as its haploid number, and the total number of chromosomes
(2N) is its diploid number. The suffix ‘ploid’ refers to chromosome
‘sets’. The haploid set of the chromosome is also known as the
genome. Structurally, eukaryotes possess large linear chromosomes
unlike prokaryotes which have circular chromosomes. In Eukaryotes
other than the nucleus chromosomes are present in mitochondria
and chloroplast too. The number of chromosomes in each somatic
cell is same for all members of a given species. The organism with
lowest number of chromosome is the nematode, Ascaris
megalocephalusunivalens which has only two chromosomes in the somatic

cells (2n=2).
Autosomes and sex chromosomes:
In a diploid cell, there are two of each kind of chromosome (termed
homologus chromosomes) except the sex chromosomes. In humans
one of the sex has two of the same kind of sex chromosomes and the
other has one of each kind. In humans there are 23 pairs of
homologous chromosomes (2n=46). The human female has 44 non
sex chromosomes, termed autosomes and one pair of homomorphic
sex chromosomes given the designation XX. The human male has 44
autosomes and one pair of heteromorphic sex chromosomes, one X
and one Y chromosome.

Structure of Chromosome: A chromosome at mitotic metaphase

consists of two symmetrical structures called chromatids. Each
chromatid contains a single DNA molecule and both chromatids are
attached to each other by centromere and become separated at the
beginning of anaphase. The chromomeres are bead like
accumulations of chromatin material that are sometimes visible
along interphase chromosomes. The chromomere bearing chromatin
has an appearance of a necklace in which several beads occur on a
string. Chromomeres are regions of tightly folded DNA and become
especially prominent in polytene chromosomes. Centromere in a
chromosome contain specific DNA sequences with special proteins
bound to them, forming a disc shaped structure, called kinetochore.
In electron microscope the kinetochore appears as a plate or cup like
disc, 0.20-0.25 nm, in diameter situated upon the primary
constriction or centromere. The chromosomes of most organisms
contain only one centromere and are known as monocentric
chromosomes. Some species have diffused centromeres, with
microtubules attached along the length of the chromosomes and are
termed holocentric chromosomes. Chromosomes of Ascaris
megalocephala are examples of diffused centromeric chromosomes.
Telomere is the chromosomal ends which prevents other
chromosomal segments to be fused with it. Besides the primary
constrictions or centromeres, chromosomes also posses secondary
constriction at any point of the chromosome and are constant in
their position and extent. These constrictions are helpful in
identifying particular chromosomes in a set. Chromosomes also
contain nucleolar organizers which are certain secondary
constrictions that contain the genes coding for 5.8S, 18S and 28S
ribosomal RNA and induce the formation of nucleoli. Sometimes the
chromosomes bear round, elongated or knob like appendages known
as satellites. The satellite remains connected with the rest of the
chromosomes by a thin chromatin filament.
Chromatin:
Chemical composition of chromatin
Chromatin consists of DNA, RNA and protein. The protein of
chromatin could be of two types: histones and non histones.
DNA: DNA is the most important chemical component of chromatin,
since it plays central role of controlling heredity and is most
conveniently measured in picograms. In addition to describing the
genome of an organism by its number of chromosomes, it is also
described by the amount of DNA in a haploid cell. This is usually
expressed as the amount of DNA per haploid cell (usually expressed
as picograms) or the number of kilobases per haploid cell and is
called the C value. This is constant for all cells of a species. For
diploid cells it is 2C. Extending the C value we reach the C-value
paradox. One immediate feature of eukaryotic organisms highlights a
specific anomaly that was detected early in molecular research. Even
though eukaryotic organisms appear to have 2-10 times as many
genes as prokaryotes, they have many orders of magnitude more
DNA in the cell. Furthermore, the amount of DNA per genome is
correlated not with the presumed evolutionary complexity of a
species. This is stated as the C value paradox: the amount of DNA in
the haploid cell of an organism is not related to its evolutionary
complexity. Lower eukaryotes in general have less DNA, such as
nematode Caenorhabditis elegans which has 20 times more DNA than E.
coli . Vertebrates have greaer DNA content about 3pg, in general
about 700 times more than E. coli . Salamander Amphiuma has a very high
DNA content of about 84pg. Man has about 3pg of DNA per haploid
genome.

Histones: Histones are basic proteins as they are enriched with basic
proteins arginine and lysine. At physiological pH they are cationic and
can interact with anionic nucleic acids. They form a highly condensed
structure. The histones are of five types called H1, H2A H2B, H3, and
H4-which are very similar among different species of eukaryotes and
have been highly conserved during evolution. H1 is the least
conserved among all and is also loosely bound with DNA. H1 histone
is absent in Sacharomyces cerevisiae.
Non-histones: In addition to histones the chromatin comprise of
many different types of non-histone proteins, which are involved in a
range of activities, including DNA replication and gene expression.
They display more diversity or are not conserved. They may also
differ between different tissues of same organism.

There are four types of chromosomes based upon the

position of the centromere in humans

1) Metacentric: In this type of chromosome the centromere occurs in

the centre and all the four chromatids are of equal length.
2) Submetacentric: In this type of chromosome the centromere is a
little away from the centre and therefore chromatids of one side are
slightly longer than the other side.
3) Acrocentric: In this type of chromosome the centromere is located
closer to one end of chromatid therefore the chromatids on opposite
side are very long. A small round structure, attached by a very thin
thread is observed on the side of shorter chromatid. The small round
structure that is a part of the chromatid is termed as satellite. The
thin strands at the satellite region are termed as Nucleolar Organiser
Region.
4) Telocentric: In this type of chromosome the centromere is placed
at one end of the chromatid and hence only one arm. Such
telocentric chromosomes are not seen in human cells.
CHROMOSOMAL ABNORMALITIES
I. Abnormalities in chromosomal number
A. nondisjunction
1. nondisjunction - mistake in cell division where chromosomes do
not separate properly in anaphase
 usually in meiosis, although in mitosis occasionally; in meiosis, can
occur in anaphase I or II 2. polyploidy – complete extra sets (3n, etc.)
– fatal in humans, most animals 3. aneuploidy – missing one copy or
have an extra copy of a single chromosome
 three copies of a chromosome in your somatic cells: trisomy
 one copy of a chromosome in your somatic cells: monosomy
 most trisomies and monosomies are lethal well before birth in
humans; exceptions covered below
 generally, autosomal aneuploids tend to be spontaneously aborted
 over 1/5 of human pregnancies are lost spontaneously after
implantation (probably closer to 1/3)
 chromosomal abnormalities are the leading known cause of
pregnancy loss
 data indicate that minimum 10-15% of conceptions have a
chromosomal abnormality
 at least 95% of these conceptions spontaneously abort (often
without being noticed)
B. aneuploidy in human sex chromosomes 1. X_ female (Turner
syndrome)
 short stature; sterile (immature sex organs); often reduced mental
abilities; about 1 in 2500 human female births 2. XXY male
(Klinefelter syndrome)
 often not detected until puberty, when female body characteristics
develop; sterile; sometimes reduced mental abilities; testosterone
shots can be used as a partial treatment; about 1 in 500 human male
births 3. XYY male (XYY syndrome)
 usually tall, with heavy acne; some correlation with mild mental
retardation and with aggressiveness; usually still fertile; about 1 in
1000 human male births
4. XXX female (triple X syndrome)
  usually just like XX females, except for having 2 Barr bodies in
somatic cells; HOWEVER, more likely to be sterile, and if fertile, more
likely to have XXY and XXX children; about 1 in 1000 human female
births
C. aneuploidy in human autosomes
1. autosomic monosomy appears to be invariably fatal, usually very
early in pregnancy
2. most autosomic trisomy is fatal, but sometimes individuals
trisomic for autosomes 13, 15, 18, 21, or 22 survive to birth and even
beyond
 chromosome number reflects size; bigger number = smaller size,
and usually fewer genes
 extra 13, 15, or 18 leads to multiple defects and usually death well
before 1 year of age BIOL 1020 – CHAPTER 15 LECTURE NOTES 2 of 2
 extra 22 is much like extra 21 (Down syndrome, covered below),
but usually more severe, with shorter life expectancy
3. trisomy 21 (Down syndrome): the only autosomal trisomy
condition in humans that allows an appreciable number of
individuals to survive to adulthood
 found in about 1 in 750 live births; a phenotypically identical
condition occurs that is not due to a true trisomy (it involves a
chromosomal translocation, covered later)
 traits include abnormal facial appearance, high likelihood of
mental retardation (degree varies considerably), and increased
likelihood of developing leukemia and Alzheimer’s disease
 likelihood of a child being born with Down syndrome increases
with the age of the mother
 rate is as high as 1 in 16 live births for mothers age 45 and over at
conception; not completely clear why the odds go up so dramatically,
likely a combination of factors; nondisjunction is more common in
eggs than sperm; appears that spontaneous rejection of aneuploid
pregnancies is more common in younger women
II. Abnormalities in chromosomal structure: chromosomal
rearrangements and fragile sites
A. in addition to nondisjunction errors, there can be errors in
homologous chromosome pairing and in crossing over; these
produce chromosomal rearrangements
1. reciprocal translocation – nonhomologous chromosomes pair and
exchange parts (if only one gets new material, this is just called a
translocation)
 can lead to deletions (loss of genetic material) and duplications
(extra copies of genetic material)
 somewhat common in humans is a translocation of chromosome
21 to chromosome 14
 results in only 45 chromosomes in body cells of carrier (has one
chr 14, one chr 21, one 14/21 = normal phenotype), but that
individual has a high chance of producing offspring that are
essentially trisomy 21 (with one chr 14, two chr 21, and one 14/21)
 this is called translocation Down syndrome, accounting for about
3% of all phenotypic Down syndrome individuals
2. inversion – part of a chromosome is “flipped” relative to the
normal gene sequence; can lead to deletions and duplications
3. deletion
 causes include losses from translocations, crossovers within an
inversion, and unequal crossing over
 can also be caused by breaking without rejoining, usually leading to
large deletions
 small deletions are less likely to be fatal; large deletions are usually
fatal – but always, there is variation based on what genes are lost
 some medium-sized deletions lead to recognizable human
disorders
 several syndromes have been described that correspond to
deletions of certain chromosomal regions; most commonly found in
live births in humans is deletion of the short arm of chr 5  called cri
du chat (cat’s cry) syndrome  found in about 1 in 50,000 live births
 surviving infants have a distinctive cry, severe mental retardation,
and shortened lifespan
4. duplication
 causes include extras from translocations, crossovers within an
inversion, and unequal crossing over
 again, amount makes a difference, with larger duplications more
likely to be fatal, but there is variation based on what genes are
duplicated
 duplications also provide raw material for genetic evolution; for
example, there are many pseudogenes in humans that are
“inactivated” duplicates B. fragile sites 1. some chromosomes have
regions that are poorly connected to the rest of the chromosome;
 the “poor connection” is often a string rich in CGG or CGC repeats,
and is inherited like a gen
e  breaks from these fragile sites lead to loss of genetic material
2. human X can have such a site (fragile X syndrome)
 effects center on decreased mental capacity  more prominent
effects in males than females
 one of the trinucleotide repeat disorders:  normally 5-55 CGG
repeats  diseased individuals have 200-1300 repeats  like many
trinucleotide repeat disorders, the repeat number may increase from
one generation to the next
3. other fragile sites may play a role in cancer