Genetics (SGS124n)
Lecture2:The Human chromosomes
Dr Samar Samir elkhateeb
Lecturer Biochemistry and Genetics
Faculty of Dentistry –MSA university
[email protected] The chromosomes
• Nucleus = library
• Chromosomes = bookshelves
• Genes = books
• Almost every cell in an organism contains the same libraries and the
same sets of books.
• Books represent all the information (DNA) that every cell in the body
needs so it can grow and carry out its various functions.
SGS 124:Genetics-Lec4; Dr. Ahemd Aref 2
Cont.
• The study of chromosomes and their abnormalities is called
cytogenetics.
• Chromosomes are thread like structures visible only during
mitosis of cell division.
• They consists of DNA, histones and non-histone proteins .
• Histone proteins are proteins with a high proportion of positively
charged amino acids ( Lysine and Arginine).
• This enable them to bind firmly to the negatively charged DNA
double helix which is important in DNA packing. 3
Cont.
• Chromosomes are folded and coiled in a complex manner.
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DNA packing
The human haploid genome contains about 3 billion nucleotide pairs.
If uncoiled, the DNA contained by each of those chromosomes would measure
between 1.7 and 8.5 m long.
This is too long to fit into a cell.
Moreover, if chromosomes were composed of extended DNA, it is difficult to
imagine how the DNA could be replicated and segregated into two daughter cells
without breaking down. 5
Cont.
• The packing of DNA into chromosomes involves:
I. Primary coiling of the DNA double helix.
II. Secondary coiling around the histone beads, forming what are
called nucleosomes.
III. Tertiary coiling of the nucleosomes to form the chromatin fiber
which are further wound in a tight coil to make up the chromosome.
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Primary coiling
Secondary coiling
Tertiary coiling
Further coiling to
form chromatin
Chromosome
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Chromosomes morphology
• Chromosomes can be classified by centromere position into four types:
1. Metacentric
2. Submetacentric
3. Acrocentric
4. Telocentric
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Cont.
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Chromosome parts
•The Centromere appears as constricted area
of the metaphase chromosome, each
chromosome has one centromere.
•During cell division, the centromere is the last
segment of chromosome to replicate and
separate .
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Cont.
• The normal chromosome ends are capped by so, called telomeres,
which play an important role in chromosome stability.
• Telomeres consist of short nucleotide sequence (TTAGGG) repeated
several thousand time.
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Cont.
• Telomeres prevent normal chromosome ends from joining each other,
whereas broken ends lacking telomeres often tend to fuse and become sticky.
• Normal chromosome duplication leads to progressive shortening of
telomeres until, after a number of cell division, the chromosomes become
unstable and the cell dies. (Apoptosis)
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Telomers and cancer
• As a cell begins to become cancerous, it divides more often and its telomeres
become very short.
• If its telomeres get too short, the cell may die.
• It can escape this fate by up-regulating an enzyme called telomerase, which
can prevent telomeres from getting shorter and even elongate them.
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What is a locus?
• A locus describes the region of a chromosome where a gene is located.
• Example:11p15.5 is the locus for the human insulin gene.
• 11 is the chromosome number, p indicates the short arm of the
chromosome and 15.5 is the number assigned to a particular region on
a chromosome.
• The numbers that follow the letter represent the position on the arm:
region 1, band 5, sub-band 5.
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Cont.
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Chromosomal abnormalities
• Chromosome abnormalities are responsible for significant proportion of
genetic diseases.
Changes
Numerical Structural
Numerical changes
Aneuploidy: loss or gain of one or
more chromosomes , this means Normal Polyploidy
that the number is not an exact
multiple of the haploid (n).
Polyploidy: the addition of one or
more complete haploid set which
means that the number is more
than 2n i.e. (3n, 4n,…..etc..)
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Cont.
Aneuploidy can be seen in 2 forms:
Trisomy: only one of the chromosomes is present threefold (2n+ 1), all other
chromosome pairs are normal.
Monosomy: one chromosome of a pair is missing.
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Cont.
Three trisomies are known affecting chromosomes 13, 18, and 21.
Trisomy 13 (Patau syndrome)
Mental and physical retardation, skull and facial abnormalities, cleft lip and
extra digit.
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Trisomy 18 (Edward syndrome)
Mental and physical retardation, skull and facial abnormalities, cardiac
abnormalities.
Trisomy 21 (Down syndrome)
Mental retardation, flat face and high risk of cardiac abnormalties.
Sex chromosomes abnormalities
XO (Turner syndrome)
Female, no sexual maturity, short stature, narrow aorta.
XXX (Super female)
V.Tall and thin, menstrual irregularity.
XXY (Klinefelter syndrome)
Male, lack of secondary sexual characteristics , breast swelling, no sperm
formation.
XYY (Jacobs syndrome)
V.Tall male, learning disabilities ,Tremors
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XO (Turner syndrome)
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Structural abnormalities
In addition to the loss or gain of whole chromosomes, parts of the chromosome
can be lost or duplicated, and rearrangement of some portions can be altered.
Alterations in the chromosome's structure can take several forms:
Translocation:
It is the transfer of a segment from one chromosome to a non homologous
chromosome .
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Cont.
There are two main types of
translocations:
Reciprocal translocation: Segments
from two different chromosomes
have been exchanged.
Robertsonian translocation: long
arms of nonhomologus
chromosomes fuse to form a single
chromosome in humans these only
occur with chromosomes 13, 14, 15,
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Inversions:
A portion of the chromosome has
broken off, turned upside down and
reattached, therefore the genetic
material is inverted.
Deletion:
A portion of the chromosome is
missing or deleted.
e.g Wolf-Hirschhorn syndrome(Greek
warrior helmet), which is caused by
partial deletion of the short arm of
chromosome 4.
Insertions:
A portion of one chromosome has been deleted from its
normal place and inserted into another chromosome.
Duplication
Presence of extra piece of chromosome which has usually
originated by unequal crossing over between homologous
chromosomes .
Isochromosome:
is a chromosome that has lost one of its arms and
replaced it with an exact copy of the other arm.
This is sometimes seen in some females with Turner
syndrome or in tumor cells.
Ring chromosome
• Is a chromosome whose arms have fused together to form a ring.
• Ring chromosomes may form in cells following genetic damage by mutagens
like radiation.
