Chromosomes pdf - D. Dhafer

  Thi -Qar University                                                                                                              Human genetic
  Medical College                                                                                                                    Lec 3
  Microbiology Department                                                                                                  Dr Dhafer A. Alghezi

Chromosomes

A chromosome is a structure that occurs within cells and contains the cell's

genetic material. The genetic material, which determines how an organism develops,
is a molecule of deoxyribonucleic acid (DNA). In prokaryotes, or cells without a
nucleus, the chromosome is merely a circle of DNA. In eukaryotes, or cells with a
distinct nucleus, chromosomes are much more complex in structure.

The structure of chromosomes

A chromosome is an organized structure of DNA and protein that is found in cells.

It  is  a  single  piece  of  coiled  DNA  containing  many  genes,  regulatory  elements  and
other  nucleotide  sequences.  Chromosomes  also  contain  DNA-bound  proteins,  which
serve  to  package  the  DNA  and  control  its  functions.  Chromosomes  vary  widely
between  different  organisms.  The  DNA  molecule  may  be  circular  or  linear,  and  can
be  composed  of  10,000  to  1,000,000,000  nucleotides  in  a  long  chain.  Two
chromosomal  regions  have  special  importance  in  the  formation  of  chromosome
aberrations: the centromeres and the telomeres.

The centromere is primary constriction of chromosomes where sister chromatids

are connected, situated in strictly imposed position of the chromosome. It divides the
chromosome  into  two  sections,  or  “arms.”  The  short  arm  of  the  chromosome  is
labeled  the  “p  arm.”  The  long  arm  of  the  chromosome  is  labeled  the  “q  arm.”  The
location  of  the  centromere  on  each  chromosome  gives  the  chromosome  its
characteristic shape, and can be used to help describe the location of specific genes.

The chromosome ends, the telomeres are rich in TTAGGG repetitive sequences,

and ensure the integrity and stability of the chromosome structure and play a role in
cell aging, in tumorigenicity and the formation of structural chromosome aberrations,
since in the absence of a telomere the chromosome structure becomes unstable and
fragments without telomeres easily adhere, opening the way for a wide variety of
disorders (Figure 1).

Figure 1: chromosome structure.

Humans have 46 chromosomes that occur in 23 pairs. Twenty-two of these pairs

are called autosomes. All of these chromosomes are found in both males and females.
One pair of chromosomes is called sex chromosomes because this pair contains the

genes that control gender. Males have the sex chromosomes X and Y, and females
have two X chromosomes.

Any cell in the body except red blood cells, which lack a nucleus, can be a source

of chromosomes for examination. In adults, it is easiest to obtain and use white blood
cells separated from a blood sample for the purpose of looking at the chromosomes.

A karyotype:

A karyotype is the characteristic chromosome complement of a eukaryote species.

It  describes  the  number  of  chromosomes,  and  what  they  look  like  under  a  light
microscope (Figure 2). The term is also used for the complete set of chromosomes in
a  species,  or  an  individual  organism.  The  study  of  whole  sets  of  chromosomes  is
sometimes  known  as  karyology.  The  preparation  and  study  of  karyotypes  is  part  of
Cytogenetics which represents a field of genetics dealing with species or cell specific
number  of  chromosomes,  and  their  structure  and  characteristic  segments,  their
functional roles, and all the differences - namely the chromosomal mutations - related
to them.

Karyotypes can be used for many purposes; such as, to study chromosomal

aberrations, cellular function, taxonomic relationships, and to gather information
about past evolutionary events.

Figure 2: Human karyotypes

Chromosome Inheritance:

Normally, an individual receives 22 pairs of autosomes and two sex

chromosomes. Each pair of autosomes carries alleles for particular traits. The alleles
can be different, as when one calls for freckles and one does not.

A. Changes in chromosomes number:

Sometimes individuals are born with either too many or too few autosomes or sex

chromosomes, most likely due to non-disjunction during meiosis.

Non-disjunction is a failure of the homologous chromosomes, or daughter

chromosomes, to separate correctly during meiosis I and meiosis II, respectively.

Non-disjunction may occur during meiosis I, when both members of a homologous
pair go into the same daughter cell. It can also occur during meiosis II, when the sister
chromatids fail to separate and both daughter chromosomes go into the same gamete.

Some abnormal eggs have 24 chromosomes, whereas others have only 22

chromosomes. If an egg with 24 chromosomes is fertilized with a normal sperm, the
result  is  a  trisomy,  so  called  because  one  type  of  chromosome  is  present  in  three
copies. If an egg with 22 chromosomes is fertilized with a normal sperm, the result is
a monosomy, so called because one type of chromosome is present in a single copy.
An abnormal number of autosomes causes a developmental abnormality. Monosomy
of all but the X chromosome is fatal. The affected infant rarely develops to full term.
Trisomy  is  usually  fatal,  though  there  are  some  exceptions.  Among  autosomal
trisomies, only trisomy 21 (Down syndrome) has a reasonable chance of survival after
birth. The chances of survival are greater when trisomy or monosomy involves the sex
chromosomes.  In normal XX females,  one of the X chromosomes becomes  a darkly
staining  mass  of  chromatin  called  a  Barr  body  (named  after  the  person  who
discovered  it).  A  Barr  body  is  an  inactive  X  chromosome.  Beyond  a  single  one
become Barr body; this explains why poly-X females and XXY males are seen fairly
frequently.

Down Syndrome: An Autosomal Trisomy:

The most common autosomal trisomy seen among humans is Down syndrome,

also called trisomy 21.

Persons with Down syndrome usually have three copies of chromosome 21

because the egg had two copies instead of one. The chances of woman having a Down
syndrome  child  increase  rapidly  with  age,  starting  at  about  age  40.  The  reasons  for
this  are  still  being  investigated.  Although  an  older  woman  is  more  likely  to  have  a
Down syndrome child, most babies with Down syndrome are born to women younger
than  age  40  because  this  is  the  age  group  having  the  most  babies.  Karyotyping  can
detect a Down syndrome child.

Down syndrome is easily recognized by these common characteristics: short

stature;  an  eyelid  fold;  a  flat  face;  stubby  fingers;  a  wide  gap  between  the  first  and
second toes;  a large, fissured tongue;  a round head; and a palm crease, the so-called
simian  line.  Unfortunately,  mental  retardation,  which  can  vary  in  intensity,  is  also  a
characteristic.  The genes that cause Down syndrome are located on the bottom third
of chromosome 21.

B. Changes in Sex chromosome number:
An abnormal sex chromosome number is a result of inheriting too many or too

few X or Y chromosomes. Turner syndrome (XO) and Klinefelter syndrome (XXY)
diseases are two examples for this changing.

Turner Syndrome:
It is a rare chromosomal condition that affects development in females. It is caused by
partial or complete loss (monosomy) of the second sex chromosome. From birth, a

girl  with  Turner  syndrome  has  only  one  sex  chromosome,  an  X  (Figure  3).  the
Turner  syndrome  female  is  a  short,  with  a  broad  chest  and  folds  of  skin  on  the
back  of  the  neck.  The  ovaries,  oviducts,  and  uterus  are  very  small  and
underdeveloped.  Turner  females  do  not  undergo  puberty  or  menstruation,  and  their
breasts do not develop.

Figure 3: Monosomy (Turner syndrome) karyotype

Klinefelter Syndrome:
It is a chromosomal variation in males in which one extra X chromosome is present,
resulting in  a XXY sex chromosome karyotype  (Figure 4). 1:  650  of  males are born
with two X chromosomes and one Y chromosome.   The symptoms of this condition
(referred to as “47, XXY”) are often so subtle that only 25% are ever diagnosed, and
those  are  usually  not  diagnosed  until  after  age  15.  Disorder  occurring  due  to
nondisjunction of the X chromosome.



The sperm containing both X and Y combines with an egg containing X,

results in a male child.



The egg may contribute the extra X chromosome.

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Males with some development of breast tissue normally seen in females.



Little body hair is present, and such person are typically tall, have small testes.



Infertility results from absent sperm.



Evidence of mental retardation may or may not be present.

Figure 4: Klinefelter Syndrome karyotype

Poly-X females:

A poly-X female has more than two X chromosomes and extra Barr bodies in the
nucleus. Females with three X chromosomes have no distinctive phenotype. Females
with more than three X chromosomes occur rarely.

Jacobs Syndrome:

XYY males with Jacobs syndrome can only result from nondisjunction during
spermatogenesis. Affected males are usually taller than average, suffer from persistent
acne, and tend to have speech and reading problems.

C. Changes in Chromosome Structure:

There are various agents in the environment, such as radiation, certain organic
chemicals or even viruses, that cause chromosome to break. Changes in chromosome
structure include deletions, translocations, duplications, and inversions of
chromosome segments.

1. An inversion: occurs when a segment of a chromosome is turned around 180

c (Figure 5)°, you might think this is not a problem because the same genes are
present, but the new position might lead to altered gene activity.

Figure 5: An inversion of chromosome

2. A deletion: occurs when an end of a chromosome breaks off or when two

simultaneous breaks lead to the loss of an internal segment (Figure 6).

Figure 6: A deletion of chromosome

3. A translocation: is the movement of a chromosome segment from one

chromosome to another non homologous chromosome (Figure 7) .
Translocation heterozygotes usually have reduced fertility due to production
of abnormal gametes.

Figure 7: A translocation of chromosome

4. A duplication: is the doubling of chromosome segment (Figure 8) . There are

several ways a duplication can occur. A broken from one chromosome can
simply attach to its homologue, or unequal crossing- over may occur leading
to a duplication and deletion.

Figure 7: A translocation of chromosome