What is Genomics?

• Genetics is the study of inheritance or

the way traits are passed down from
one generation to another (eye
color,hair).
• Genomics is a newer term describing
the study of all of a person’s genes and
the interactions of those genes with
each other and with the environment
 GENOMICS refers to those
conditions plus ….
• Discoveries from the Human Genome
Project (HGP) which show that most
adult onset and chronic diseases can
be partially caused or prevented by
genetic factors
• Environmental factors also play a
significant role
 Importance of Genomics
• Genomics have a role in 9 of the 10 leading
causes of death in the US
• All humans have 99.9% identical genetic
makeup
• The remaining 0.1% difference may provide
useful information about diseases
• The goal of genetics is to show why some
people get sick from certain infections and
environmental changes while others do not
 Human Genome Project(HGP)
• A 13 year project where all of the genes in the
human DNA were discovered
• Determined the sequences of approximately 3
billion chemical base pairs that make up the
human DNA
• Completed in 2003 by the U.S. Department of
Energy and the National Institutes of Health with
help from many other countries including Japan,
Germany and France
 What are genetic disorders?
• A disease caused in whole or in part by
a variation or mutation of a gene
• Researchers are discovering that nearly
all diseases have a genetic component
• Some are caused by a mutation in the
gene or group of genes in a person’s
cells
• These may be random or from
environmental exposure such as cigarette
smoke
• Others are hereditary
• the mutated gene is passed down
through the family
• Most are multifactorial inheritance
disorders
• -caused by a combination of small
variations in genes, often connected with
environmental factors
 Three Categories of Genetic Disorders

• 1) Single Gene Disorders

• Caused by a mutation in a single gene.
The mutation may be present on one or
both chromosomes
• Such as Sickle cell disease, cystic fibrosis
• 2) Chromosome Disorders
• -caused by an excess or deficiency of
genes on the chromosomes or structural
changes within chromosomes
• -Down syndrome
• 3) Multifactorial Inheritance Disorders are
rare disorders caused by mutations in non-
chromosomal DNA located within the
mitochondria.
• These disorders can be found to affect any part of
the body including the brain and the muscles

• -heart disease, most cancers, and behavioral

disorders such as alcoholism, obesity, mental
illness, and Alzheimer’s disease are examples
• Genes are also known to play a role in the
occurrence of infectious diseases like tuberculosis
and AIDS as well as some non communicable
diseases like cancer and diabetes
 Monogenic diseases
• result from modifications in a single gene occurring
in all cells of the body.
• Though relatively rare, they affect millions of
people worldwide.
• Scientists currently estimate that over 10,000 of
human diseases are known to be monogenic.
• Pure genetic diseases are caused by a single error
in a single gene in the human DNA. The nature of
disease depends on the functions performed by
the modified gene.
• The single-gene or monogenic diseases can
be classified into three main categories:
• 1) Dominant: that involve damage to only one gene
copy
• 2) Recessive : occur due to damages in both copies
or allele
• 3) X-linked: are linked to defective genes on the X
chromosome which is the sex chromosome. The X
linked alleles can also be dominant or recessive.
• Monogenic diseases are responsible for a heavy
loss of life. The global prevalence of all single gene
diseases at birth is approximately 10/1000.
 Thalassemia
• Thalassemia is a blood related genetic disorder
which involves the absence of or errors in genes
responsible for production of haemoglobin, a
protein present in the red blood cells.
• Each red blood cell can contain between 240
and 300 million molecules of haemoglobin.
• The severity of the disease depends on the
mutations involved in the genes, and their
interplay.
 Sickle-cell anemia
• is a blood related disorder that affects the
haemoglobin molecule, and causes the entire
blood cell to change shape under stressed
conditions.
• In sickle cell anaemia, the haemoglobin molecule
is defective. After haemoglobin molecules give
up their oxygen, some may cluster together and
form long, rod-like structures which become stiff
and assume sickle shape.
• and cause blockages that deprive organs and
tissues of oxygen-carrying blood
 Haemophilia
• Haemophilia is a hereditary bleeding disorder, in
which there is a partial or total lack of an essential
blood clotting factor.
• It is a lifelong disorder, that results in excessive
bleeding, and many times spontaneous bleeding,
which, very often , is internal.
• Haemophilia A is the most common form, referred
to as classical haemophilia. It is the result of a
deficiency in clotting factor 8, while haemophilia B
(Christmas Disease) is a deficiency in clotting
factor 9.
• This illness is a sex-linked recessive disorder.
 Cystic Fibrosis
• a genetic disorder that affects the respiratory, digestive and
reproductive systems involving the production of
abnormally thick mucus linings in the lungs and can lead to
fatal lung infections.
• The disease can also result in various obstructions of the
pancreas, hindering digestion.
• An individual must inherit two defective cystic fibrosis
genes, one from each parent, to have the disease.
• Each time two carriers of the disease conceive, there is a
25 percent chance of passing cystic fibrosis to their
children ; a 50 percent chance that the child will be a
carrier of the cystic fibrosis gene; and a 25 percent chance
that the child will be a non-carrier.
 Huntington’s disease
• a degenerative brain disorder, in which afflicted individuals
lose their ability to walk, talk, think, and reason.
• They easily become depressed, and lose their short-term
memory capacity.
• They may also experience a lack of concentration and
focus. This disease begins between ages 30-45, and every
individual with the gene for the disease will eventually
develop the disease.
• Huntington's is an autosomal dominant genetic disorder
which means that if one parent carriers the defective
Huntington's gene, his/her offspring have a 50/50 chance of
inheriting the disease.
 Genes and chromosomal diseases
• Down Syndrome
• a type of mental retardation caused by extra genetic
material in chromosome 21.
• This can be due to a process called nondisjunction, in
which genetic materials fail to separate during a crucial part
of the formation of gametes, resulting in an extra
chromosome (called trisomy 21).
• The cause of nondisjunction is not known, although it
correlates with a woman’s age reference. The additional
material present influences development and results in the
state known as Down Syndrome.
• Some physical characteristics of Down Syndrome
in infants are decreased muscle tone, a flat face,
eyes slanting up, irregular shaped ears, ability to
extend joints beyond the usual, large space
between the big toe and its neighbouring toe, large
tongue relative to the mouth, etc.

• Down Syndrome patients can also be afflicted with

other conditions, including heart disease,
Alzheimer’s disease, and leukaemia.
Genes and noncommunicable diseases
• Most diseases involve many genes in complex
interactions, in addition to environmental
influences.
• An individual may not be born with a disease but
may be at high risk of acquiring it. This is called as
genetic predisposition or susceptibility.
• The genetic susceptibility to a particular disease
due to the presence of one or more gene
mutations, and/or a combination of alleles need not
necessarily be abnormal.
• major noncommunicable diseases, like cancer,
diabetes, cardiovascular disease, asthma, and
some mental illnesses.
• In some cases, such as cancer, individuals are
born with genes that are altered by lifestyle
habits or exposure to chemicals.
• Cancer, for example, may involve tumour-
suppressor genes, genes which suppress
tumour formation, which lose their function, thus
giving rise to carcinomas.
• Cardiovascular disease tends to manifest itself in
specific ways unique to various communities.
• For example, African communities tend to have
strokes as a result of cardiovascular disease,
while south asians tend to have heart attacks.

• Understanding genetic predisposition to disease

and knowledge of lifestyle modifications that either
exacerbate the condition or that lessen the
potential for diseases (i.e., no smoking or drinking)
is necessary for the public to make informed
choices.
 Genes and communicable diseases
• In addition to diseases which have an inherent genetic
component or a genetic influence, there are some major
communicable diseases which can be treated with genetic
based interventions,
• HIV/AIDS, tuberculosis, and malaria

• For each of these diseases, genomic interventions are

being conducted in all over the world. In the Health
Professionals Resources section, one can find examples of
best practices in genomics applications to these common
diseases.
 Genetic Testing
• Today more than 900 genetic tests are
available.
• There are also susceptibility tests which can
determine an estimated risk for developing the
disease
• List of common tests available:
http://www.ornl.gov/sci/techresources/Human_Genome/
medicine/genetest.shtml
• Database for the entire human genome
• www.genome.gov
 Genetic Testing: How it Works
• Scientists scan a patient’s DNA for mutated
sequences
• The DNA sample can come from any tissue
including blood
• For some tests, probes, short pieces of DNA, are
designed with sequences complimentary to the
mutated sequence
• The probe will seek its compliment
among the base pairs and will bind to it
and flag the mutation
• Other tests compare the bases in a
patient’s gene to that of a normal gene
 Genetic Tests: Types Available
1. Carrier Screening
•Identifies unaffected individuals who carry one copy
of the gene that needs two to express the disease
2. Preimplantation genetic diagnosis
• embryo from in vitro fertilization is tested
before implanted in the uterus
3. Prenatal Diagnostic Testing

4. Newborn screening
Prenatal diagnostic testing: What tests show

• Neural tube defects

• Birth defects of the brain or spinal cord
• Chromosomal Abnormalities
• Indicated by abnormal amounts of substances in
the mother’s blood such as alfa-feto protein and
estriol
• Most fetuses with these abnormalities die before
birth
 Prenatal diagnostic testing:Types of tests

1.Ultrasonography
• Performed before other tests to detect obvious
structural defects in the fetus
• Chorionic Villus Sampling
• A doctor removes a small sample of the chorionic
villi, which are small projections that make up part
of the placenta
• Can be done between 10-12 weeks of pregnancy
so the diagnosis is earlier
2. Amniocentesis
•One of the most
common prenatal tests

•A sample of amniotic
fluid is removed and
tested for alpha-
fetoprotein level
 Benefits of Genetic Testing
• Some tests can clarify a diagnosis for a
more concise treatment
• Other tests can prevent families from
having children with devastating
diseases
 Disadvantages of Genetic Testing

• They only give a probability for developing the

disorder
• People who carry the mutation may never develop the
disorder
• Possibility for errors due to contamination or
misidentification
• Cost can range from hundreds to thousands of dollars
• Currently we treat most diseases by trying to reduce the
symptoms. Often we don’t understand the biological basis.
• By finding the genes involved and then determining the
proteins they code for, we will learn the biological basis of
diseases.
• It may then be possible to target the cause, not the
symptom.
• It might also be possible to slow down or prevent the onset
of adult diseases if we understood the biological basis.
• Pharmacogenomics realizes that we react different to
medications because of metabolizing enzymes, etc. and
that is controlled by genes.