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Introduction to Genetic
Dr Rosline Hassan
Department of Haematology
School of Medical Sciences
University Sains Malaysia
Table of contents
Chromosome
DNA
Protein synthesis
Mutation
Genetic disorder
Relationship between genes and cancer
Genetic testing
Technical concern
Chromosome
All living organisms
consist of cells.
In each cell there is
chromosomes.
Chromosomes are
strings of DNA
Chromosome consists
of genes, blocks of
DNA.
Each gene encodes a
particular protein.
Chromosome
Each gene has its own position in the
chromosome.
This position is called locus.
Complete set of genetic material (all
chromosomes) is called genome.
Particular set of genes in genome is called
genotype.
The genotype is with later development after
birth base for the organism's phenotype, its
physical and mental characteristics, such as
eye color, intelligence etc.
DNA
DNA is a double
helix composed of
two intertwined
nucleotide chains
oriented in opposite
directions.
The double helix
composed of
building block called
nucleotides
DNA
Each nucleotides
consist :
Phosphate group
Deoxyribose sugar
molecule
One of four different
nitrogenous bases
either Purines - Adenine
and Guanine, or Pyrimidines
-Cytosine and Thymine)
DNA
The functional units of DNA are genes.
A gene is a segment of DNA that can be
copied to make RNA.
The nucleotide sequence in RNA is translated
into the amino acid sequence of a protein.
Proteins are the main determinants of the
basic structural and physiological properties
of an organism.
Protein synthesis
DNA is duplicated
before a cell
divides
A process called
replication
Protein synthesis
Genes are transcribed
into RNA
(transcription).
Non-coding parts are
removed called mRNA
Transported out of the
nucleus
Outside the nucleus,
the proteins are built
(translation).
Mutation
Mutations
Inherited
Carrier or diseased
Acquired
Caused by radiation, toxins, diet,
infections
Mutation
Variation within a species may be from
hereditary variation, environmental variation,
or both.
The newly created offspring can then be
mutated.
Mutation means that the elements of DNA
are a bit changed.
The effect of mutation depends on both the
mutation and its location
Mutation
Errors in the replication of DNA have been
postulated as being responsible for the
mutations seen in conditions such as
Huntington's disease2 and myotonic
dystrophy.
Errors in recombination are responsible for
mutations called translocations, such as occur
in leukemias and other cancers.
Normal recombination produces genetic
variation by the exchange of genetic material
between paired chromosomes.
Mutation
Mutations can arise
through a variety of
mechanisms range from
changes in a single
nucleotide to the loss,
duplication or
rearrangement of entire
chromosomes.
When a gene contains a
mutation, the protein
encoded by that gene will
be abnormal and
sometimes changes are
insignificant
Mutation
Some mutations are silent; they affect neither
the structure of the encoded protein nor its
function.
Other mutations result in an altered protein.
Certain chemicals produce DNA damage that
leads to mutation, tobacco smoke, certain
dyes and chemotherapeutic agents
Alleles
Genes come in pairs,
with one copy inherited
from each parent.
Many genes come in a
number of variant forms,
known as alleles.
A dominant allele
prevails over a normal
allele.
A recessive gene
becomes apparent if its
counterpart allele on the
other chromosome
becomes inactivated or
lost.
Dominant genes
In dominant genetic
disorders, if one
affected parent has a
disease-causing allele
that dominates its
normal counterpart,
each child in the family
has a 50-percent
chance of inheriting the
disease allele and the
disorder.
Recessive genes
In diseases associated with
altered recessive genes, both
parents - though diseasefree themselves- carry one
normal allele and one altered
allele.
Each child has one chance in
four of inheriting two altered
alleles and developing the
disorder;
one chance in four of
inheriting two normal alleles,
two chances in four of
inheriting one normal and
one altered allele, and being
a carrier like both parents.
Genetic disorders
Chromosome
Abnormalities
A karyotype is a
display of the
chromosomes of a
single cell.
Genetic disorders
Single-Gene Disorders
Some disorders due to a
single gene to be
altered or missing.
Example is sickle-cell
anemia.
Mutations in the betaglobin gene cause blood
cells to become a sickle
shape.
The sickle cell easily get
clogged in the narrow
passages.
Genetic disorders
Multifactorial Disorders
Multifactorial disorders result from mutations
in multiple genes, often coupled with
environmental causes. The complicated bases
of these diseases make them difficult to study
and to treat.
Heart disorder, diabetes and cancer are
examples of this type of disorder.
What is the relationship
between genes and cancer?
All cancer is genetic
It is triggered by altered genes.
A small portion of cancer is inherited
A mutation carried in reproductive cells,
passed on from one generation to the
next, and present in cells throughout
the body.
What is the relationship
between genes and cancer?
Most cancers come from random
mutations that develop in body cells
during one's lifetime - either as a
mistake when cells are going through
cell division or in response to injuries
from environmental agents such as
radiation or chemicals.
What is the relationship
between genes and cancer?
Cancer usually arises in a single cell.
The cell's progress from normal to malignant
to metastatic appears to follow a series of
distinct steps, each one controlled by a
different gene or set of genes.
Several types of genes have been implicated.
Oncogenes normally encourage cell growth;
when mutated or overexpressed
Tumor-suppressor genes normally restrain cell
growth
What is Genetic Testing?
Means a laboratory test of a person’s
genes or chromosomes for
abnormalities, defects, or deficiencies,
including carrier status, that are linked
to physical or mental disorders or
impairments or a susceptibility to them.
Genetic testing
How do they test?
Testing for extra
chromosomes
Testing of DNA
Testing for a protein
Genetic testing
In clinical research programs, doctors make
use of genetic tests :
early detection (familial adenomatous polyposis)
genes prompt close surveillance for colon cancer);
diagnosis (different types of Leukaemia can be
distinguished);
prognosis (the product of a mutated p53 tumour
suppressor gene) flags cancers that are likely to
grow aggressively); and
treatment (antibodies block a gene product that
promotes the growth of breast cancer).
Genetic testing
Methods for detecting genetic
abnormalities, depend upon the size
and nature of the mutation.
Some techniques are applied to test for
chromosomal DNA itself, some to the
RNA copies and some to the protein
product of the gene
Genetic testing
Single base pair mutations can be identified
by any of the following methods:
Direct sequencing, which involves identifying
each individual base pair, in sequence, and
comparing the sequence to that of the normal
gene
This tends to be a labour-intensive method
reserved for previously unidentified mutations
or rare mutations of a common disease (such
as cystic fibrosis), when other methods do not
detect the disease that is clinically suspected.
Genetic testing
Larger mutations involve the deletion,
rearrangement, expansion or duplication
of parts of genes, entire genes or
multiple genes:
A number of strategies use the
polymerase chain reaction to amplify
specifically the region involving the
mutation.
Genetic testing
Results of genetic tests could show:
Genetic diseases
Will get or already has the disease
Genetic predispositions
Could, maybe, might get the disease
Genetic Tests Find
Mutations, NOT Disease
Women with the BRCA1 breast cancer
susceptibility gene have an 80-percent
chance of developing breast cancer by
the age of 65.
The risk is high but not absolute
Family members who negative for the
BRCA1 mutation are not exempt from
breast cancer risk
over time, they can acquire breast
cancer-associated genetic changes at
the same rate as the general population
Technical Concerns
Before predictive gene tests become
generally available, specialists and
society must come to grips with major
technical, ethical, and economic
concerns.
If widespread gene testing becomes a
reality, it will be necessary to develop
tests that are simple, cost-effective,
and accurate.
Technical Concerns
Testing thousands to millions of people
will require many new labs and
personnel as well as more genetic
counselors.
Widespread gene testing will require
many health care providers have a
basic understanding of genetic
principles in order to interpret the tests.
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