GENETICS & HEALTH

Alka Mishra
M. Sc. Nursing 1st year
 Content
• Definition
• Genetic disorders
• Disease burden
• Human genomic project
• Gene therapy
• Preventive and social measures in genetics
• Research in India
• Genetic services
 DEFINITION
• Genetics is the study of gene, heredity,
and genetic variation in living organisms. It
is generally considered a field of biology,
but it intersects frequently with many of the
life sciences and is strongly linked with the
study of information systems.
 HISTORY
• The father of genetics is Gregor Mendel, a
late 19th-century scientist . Mendel studied
'trait inheritance', patterns in the way traits
were handed down from parents to
offspring. He observed that organisms
(pea plants) inherit traits by way of
discrete "units of inheritance". This term,
still used today, is a somewhat ambiguous
definition of what is referred to as a gene.
 HISTORY
• Trait inheritance and molecular inheritance
mechanisms of genes are still a primary
principle of genetics in the 21st century,
but modern genetics has expanded
beyond inheritance to studying the
function and behaviour of genes.
 HISTORY
• Gene structure and function, variation, and
distribution are studied within the context
of the cell, the organism (e.g. dominance)
and within the context of a population.
Genetics has given rise to a number of
sub-fields including epigenetics and
population genetics
 HISTORY
• Organisms studied within the broad field span
the domain of life, including bacteria, plants,
animals, and humans.
• Genetic processes work in combination with
an organism's environment and experiences
to influence development and behaviour,
often referred to as nature versus nurture.
The intra- or extra-cellular environment of a
cell or organism may switch gene
transcription on or off.
 Burden Of Genetic Disorders

• Each year more than 3 million children born

with a serious genetic defect die; most of
these deaths (90%) occur in developing
countries. In the western world, there is 1%
chance of having an inherited disease at
birth. Approximately 5% of the world’s
population carries trait genes for
haemoglobin disorders, mainly sickle-cell
disease and thalassemia. Over 300 000
babies with severe haemoglobin disorders
are born each year.
 Conted.........
• The estimated incidence of Down
Syndrome is 1 in 1,000 live births
worldwide.
• Each year approximately 3,000 to 5,000
children are born with this chromosome
disorder and it is believed there are about
250,000 families in the United States of
America who are affected by Down
Syndrome.
 Conted.....
• The incidence of Cystic Fibrosis varies
across the globe. Although it is severely
under diagnosed in Asia, existing evidence
indicates that the prevalence of CF is rare.
In the United States of America the
incidence of CF is reported to be 1 in
every 3500 births.
 BURDEN OF GENETIC DISORDERS IN INDIA
S.No. Disorder Incidence Births/ year

1. Congenital Malformation 1 : 50 678,000

2. Down Syndrome 1 : 800 34,000

3. Metabolic Disorders 1: 1200 22,500

4. B- Thalassemia & Sickle cell 1: 1700 16,700

disease

Congenital Hypothyroidism
5. 1: 2500 10,900
Duchenne muscular
6. 1: 10,000 2,700
dystrophy

7. 1: 10,000 2,700
Spinal muscular atrophy
Source : Centre of Medical Genetics, New Delhi,2011
 BURDEN OF NCD IN INDIA
Disease Prevalence/ 1000 Cases in Deaths in
millions/ year millions / year

Diabetes 62.4 37.7 0.11

Mellitus
Ischemic Heart 37 22.3 0.55
Disease
1.54 1.64 0.63
Stroke
159.4 94.8 -----
Hypertension
 REASONS OF HIGH PREVELANCE IN INDIA
• Consanguineous marriages
• High birth rate
• Poor governmental support facilities
• Lack of expertise in genetic counseling
• Lack of improved diagnostic facilities
 CLASSIFICATION
Classification of diseases based on their
genetic basis as

• Monogenic (Mendelian) disorders

• Chromosomal aberrations
• Polygenic disorders
 Mendelian disorders
6 general patterns of inheritance are observed:
• Autosomal recessive
• Autosomal dominant
• X-linked recessive
• X-linked dominant
• Co-dominant
• Mitochondrial
 Mendelian disorders
Autosomal recessive
• The disease appears in
male and female children
of unaffected parents.
e.g., Cystic Fibrosis,
Phenylketonuria
 Mendelian disorders
Autosomal dominant
• Affected males and
females appear in each
generation of the pedigree.
• Affected mothers and
fathers transmit the
phenotype to both sons
and daughters.
• e.g., Neurofibromatosis,
Adult polycystic kidney
disease
 Mendelian disorders
X-linked recessive
• Many more males than
females show the
disorder.
• All the daughters of an
affected male are
“carriers”.
• None of the sons of an
affected male show the
disorder or are carriers.
• e.g., Hemophilia A and
B, Colour blindness
 Mendelian disorders
X-linked dominant
• Affected males pass the
disorder to all daughters
but to none of their sons.
• Affected heterozygous
females married to
unaffected males pass the
condition to half their
sons and daughters
• e.g. Vitamin D resistant
rickets, Familial
hypophosphatemia
 Mendelian disorders
Co-dominant inheritance

• Two different versions

(alleles) of a gene can be
expressed, and each
version makes a slightly
different protein
• Both alleles influence the
genetic trait or determine
the characteristics of the
genetic condition.
• E.g. ABO locus
 Mendelian disorders
Mitochondrial inheritance
• This type of inheritance
applies to genes in
mitochondrial DNA
• Mitochondrial disorders
can appear in every
generation of a family
and can affect both males
and females, but fathers
do not pass mitochondrial
traits to their children.
• E.g. Leber's hereditary
optic neuropathy (LHON)
 CHROMOSOMAL ABERRATIONS
• Alternations in the number or
structure of chromosomes
• Autosomes or sex
chromosomes
• Numerical abnormalities –
– Polyploidy ,
– Trisomy : Klienfelter’s
syndrome
– Monosomy : Turner’s
syndrome
• Structural abnormalities -
breakage followed by loss or
rearrangement deletion,
translocation. E.g. in CML, or
due to exposure to radiation
MULTIFACTORIAL INHERITANCE (POLYGENIC)
• Influence of multiple genes and environmental factors
• These include mainly the non-
communicable diseases
– Diabetes mellitus
– Hypertension
– Cardiovascular diseases
– Cancers
 Most diseases have a genetic component
• In many cases, a single defective gene is not sufficient to cause
a genetic disorder. Yet many of the common diseases of adult life,
such as diabetes mellitus, hypertension, schizophrenia, and most
common congenital malformations, such as cleft lip, cleft palate,
neural tube defects, have a strong genetic component to their
occurrence. It is thought that a large number of genes each act in a
small but significant manner to predispose an individual to the
genetic disease.
• Polygenic genetic diseases are those which are caused by the
impact of many different genes, each having only a small individual
impact on the final condition. Multifactorial traits are those which
result from an interaction between multiple genes and often multiple
environmental factors for example Some vegetarians with
'acceptable' cholesterol levels suffer myocardial infarction in the
30's. Other individuals seem to live forever despite personal stress,
smoking, obesity and sedentary lifestyle.
 Most diseases have a genetic component

Cystic fibrosis, DM, HT, Heart RSA, TB,

Trisomy21, disease, Struck by
fragile X, obesity, lightening,
Hemophillia schizophrenia, Meningococcal
Asthma infection
 Genetics v/s genomics
• Genetics:
– Conditions caused by an extra or missing
chromosome or part of a chromosome, caused by a
mutation in a single gene in chromosome or in a
mitochondria.
– Are important to the individuals and families who have
them
• 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
 HUMAN GENOME PROJECT

• In 1990 this project was initiated as joint

effort of U.S. Department of Energy and
the National Institutes of Health. In April
2003 Human Genomic Project sequencing
is completed and Project is declared
finished two years ahead of schedule.
 HUMAN GENOME PROJECT

• Improve diagnosis of disease

• Detect genetic predispositions to disease:
• screening
• advice
• risk factor modification
• Create drugs based on molecular information
• Design “custom drugs” (pharmacogenomics) based on
individual genetic profiles
• Use gene therapy for treatment
• Identify potential suspects whose DNA may match
evidence left at crime scenes
• Exonerate persons wrongly accused of crimes
 PHARMACOGENOMICS

• The development of drugs tailored to specific

subpopulations based on genes.
Pharmacogenomics has the potential to:
• Decrease side effects of drugs
• Increase drug effectiveness
• Make drug development faster and less costly
• use of medications otherwise rejected because of side
effects
• new medications for specific genotypic disease
subtypes.
•
 GENE THERAPY

• Gene Therapy is Introduction of normal genes into

cells that contain defective genes to reconstitute a
missing protein product. Gene therapy is used to
correct a deficient phenotype so that sufficient
amounts of a normal gene product are
synthesized to improve a genetic disorder.
Modification of cells by transferring desired gene
sequences into the genome. Delivery systems
available:
– In vivo: delivery of genes takes place in the body
– Ex vivo: delivery takes place out of the body, and then
cells are placed back into the body
 GENE THERAPY

• In vivo techniques usually utilize viral

vectors,Virus; carrier of desired gene, e.g.
adenovirus, retroviruses, herpes simplex virus.
Virus is usually “crippled” to disable its ability to
cause disease. Viral methods have proved to be
the most efficient to date. Many viral vectors can
stably integrate the desired gene into the target
cell’s genome.
• Ex vivo manipulation techniques
asElectroporation, Liposomes Calcium phosphate,
Gold bullets (fired within helium pressurized gun),
Retrotransposons (jumping gene), Human artificial
chromosomes.
 PREVANTIVE AND SOCIAL MEASURES IN
GENETICS

• Health promotional measures

– Eugenics: Positive and Negative Eugenics
– Euthenics
– Genetic counseling
– Nutritional genomics
• Specific protection
• Early diagnosis and treatment
• Rehabilitation
 1)Health Promotion Measures
• Eugenics:
• In 1883 Fracis Galton coins the word
‘Eugenics’ from the Greek for good (‘eu’)
and born (‘genics’).
• It is defined as “the science of
improvement of the human race through
better breeding.” It is of two types, Positive
eugenics and negative eugenecis.
 POSITIVE EUGENICS
• promotes marriage and
breeding between people
considered "desirable",
and though a positive
Eugenist may view certain
persons as "undesirable",
they will not initiate in
such practices as non-
voluntary sterilization,
genocide, active
euthanasia, or any other
forms of violence
 Conted.....
• In fact, as these eugenists say that, “the
defective will always be with us, since
people with hereditary defects come from
the general population and not strictly,
from other defectives there is no logical
way to get rid of them. By promoting
marriage and unions between Desirables,
it may be possible to increase the national
even universal average in the course of
four or so generations”
 NEGATIVE EUGENICS
• Negative eugenics: improving the quality of
the human race by eliminating or excluding
biologically inferior people from the
population.
• This goal required severe restrictions on
reproductive rights, for those with "defects"
had to be kept from reproducing, if
necessary through the forceful sterilization.
• Elderly and sick people killed under Hitler's
policy of eugenics.
 EUTHENICS
• Euthenics is a science concerned with improving the
well-being of mankind through improvement of the
environment.
• Mere improvement of genotype is of no use unless the
improved genotype is given access to a suitable
environment, which will enable the gene to express
themselves readily. E.g. Children with mild mental
retardation when placed in an encouraging environment
showed improvement in their IQ.
• Euthenics measures must be comprehensive to include
physical, intellectual, social & cultural components
whereby genetically disadvantaged individuals can
achieve a reasonable degree of development. Measures
must be aimed at improving the environment in order to
improve health, appearance, behavior, or well-being of
society.
 GENETIC COUNSELLING

• The genetic is done by a genetic counselor who is

a health professional who is academically and
clinically prepared to provide genetic services to
individuals and families seeking information about
the occurrence, of risk of occurrence, of a genetic
condition or birth defect.
• The counselor provides client-centered,
supportive counseling regarding the issues,
concerns, and experiences meaningful to the
client’s circumstances.
 GENETIC COUNSELLING
• The genetic counselor communicates
– Genetic,
– Medical and
– Technical information
• in a comprehensive, understandable
manner with knowledge of psychosocial
and cultural background of each client and
their family.
 Prenatal Genetic Counseling
• Preconception Counseling: if learned prior to
conception that female and/or her partner are
at high risk for having a child with a severe or
fatal defect.
• Options will be:
– Pre-implantation diagnosis - when eggs that have been
fertilized in vitro (in a laboratory, outside of the
womb) are tested for defects at the 8-cell (blastocyst)
stage, and only non-affected blastocysts are implanted
in the uterus to establish a pregnancy
– Using donor sperm or donor eggs
– Adoption
 Indications for Prenatal Diagnosis
• Aadvanced maternal age •Family history of other
• Previous child with a congenital structural
chromosome abnormality abnormalities
• Family history of a •Abnormalities identified
chromosome abnormality in pregnancy
• Family history of single •Other high risk factors
gene disorder (consanguinity, poor
• Family history of neural obstetric history, maternal
tube defect (NTD)
illnesses)
 Prenatal screening for genetic disorders
• Invasive testing: • Non-invasive testing:

− Amniocentesis − Ultrasonography
− Chorionic villus − Maternal serum AFP
sampling (CVS) − Isolation of foetal cells
− Cordocentesis from maternal
− Preimplatation genetic circulation
diagnosis
− Fetoscopy
 Process of Genetic Counselling
1) Benificeries: Individual or couple-

• Have affected child

• Are carriers
• Have genetic disease in family
• Have recurrent abortions
• High maternal/paternal age
• Exposed to a mutagen/teratogenic
• Are consanguineous
 Process of Genetic Counselling
• 2) Reaching accurate diagnosis:
• Family history
• Physical/clinical examination
• Cytogenetic studies/radiology
• Laboratory/DNA analysis
 Process of Genetic Counselling
• 3) Estimation of Recurrence Risk-
• Family pedigree
• Applying various methods
• Risk calculation
• -Mendel's
 Process of Genetic Counselling
• 4) Genetic Counseling –
• Available options
• Risk calculations
• New developments
• Disease course
• Treatment availability
 Process of Genetic Counselling
• 5) Decision making-
• Knowledge of disease recurrence
• Available options
• Family pressure
• Religious beliefs
• Social status
• Economic status
• Community influence
 Process of Genetic Counselling
• 6) Gene Therapy-
• In vivo
• Ex vivo
 Nutritional Genomics
• The study of how different foods can
interact with particular genes and alter the
diseases process, as in type 2 diabetes,
obesity, heart disease and some cancers.
It’s beneficial as well as harmful up to
some extent. As food stuffs containing anti
–oxidents.
 Nutritional Genomics
• Potential Benefits:
– Increased focus on a healthy diet and lifestyle
– Motivate positive behavior change
– Improved health and quality of life
– Focus on prevention
– Decreased morbidity and premature mortality
– Reduced health care costs
– Identify subgroups who might be particularly
responsive or resistant to environmental (dietary)
intervention
– Better understanding of the mechanisms involved in
disease susceptibility
 Nutritional Genomics
• Potential Harms:
– Focus on specific nutrients/foods
– Attention is drawn away from other modifiable
risk factors
– Decreased use of other services
– False sense of security
– Misleading claims
– Increased costs associated with personalized
diets and designer foods.
 2)SPECIFIC PROTECTION

• Protection of individuals and whole

community against mutagens such as X-rays
and other ionizing radiations.
• Patients undergoing X-ray examination
should be protected against unnecessary
exposure of gonads to radiations.
• Prevention of Rh hemolytic disease of
newborn by immunization with anti-D globulin
 3) EARLY DIAGNOSIS AND TREATMENT

• Post-implantation: Received a diagnosis of a

severe or fatal defect after conception. Possible
options may include : -
– Preparing family for the challenges they will face
when they have a baby
– Fetal surgery to repair the defect before birth (surgery
can only be used to treat some defects, such as spina
bifida or congenital diaphragmatic hernia. Most
defects cannot be surgically repaired.)
– Ending the pregnancy: For some families, knowing
that they'll have an infant with a severe or fatal
genetic condition seems too much to bear.
 EARLY DIAGNOSIS AND TREATMENT
– Referral to cardiologist to discuss heart
surgery, and a neonatologist to discuss the
care of a post-operative newborn.
– Carrier screening for thalassemia and
hemoglobinopathies should be offered to a
woman if she and/or her partner are having a
positive family history.
– Ideally, this screening should be done pre -
conceptionally or as early as possible in the
pregnancy.
 4) Rehabilitation

• Rehabilitation:
Early referral of
children with
genetic disorders
which are known
to cause physical
or mental
disability.
 RESEARCH IN INDIA

• In India National Centre of Applied Human

Genetics was started in March 1980 at the
Institute of Medical Sciences, Banaras Hindu
University followed by establishing Human
Genetics in a university setting at Jawaharlal
Nehru University since March 1989. In April
2002 Human Genetics Laboratory of JNU
was announced as National Centre of Applied
Human Genetics.
 Research institutes in India
– NII (National Institute of Immunology) New Delhi.
– NCCS (National Centre for Cell Science) Pune.
– CDFD (Centre for DNA Fingerprinting and Diagnostics)
Hyderabad.
– NBRC (National Brain Research Centre) Manesar.
– Institute for Bio resources and Sustainable Development,
Imphal.
– Institute of Life Sciences, Bhubaneswar.
– Bharat Immunological and Biological Corporation Limited,
Bulandshehar.
– Indian Vaccines Corporation Limited Gurgaon.
• These institutions are equipped with world-class
instrumentation and have been provided with highly
competent human resources
 GENETIC SERVICES
• Medical termination of Pregnancy 1971 lays down legislative
framework of application of genetics science
• PC-PNDT act 1974-
• Sex Selective abortions need to be eliminated by
implementation of PC-PNDT Act.
• Antenatal clinics provide opportunity to educate individual &
family on genetics.
• Screening of Antenatal mothers for Rh grouping
• Avoidance of teratogenic drugs & radiation
• Promoting immunization against rubella before pregnancy is
preventive genetics.
• Contraception for limiting the size of family & bearing children
at right age is a example of positive & preventive genetics.
 GENETIC SERVICES
• Improving nutritional status & consumption of
Iron & folic acid
• Use of Ultrasonography to detect defective
children is essentially a good screening
activity.
• Early childhood development services in
ICDS programme by providing environmental
stimuli is an attempt to realize full potential of
genetic endowment of young children
 SUMMARY

• Genetics is a study of inheritance dealing

with the transmission of hereditary characters
from one generation to another. Human
genetics is concerned with the inheritance of
human traits & their relationship to the human
health. Deals with the hereditary disorders &
provide key to their prevention & control.
 CONCLUSION

• Genetics is the branch of medicine which

has huge potential for researches, which
will help in prevention early diagnosis and
cure of diseases. As most of the diseases
has a more or less of genetic component it
will help in creating more productive and
disease free society.
 BIBLIOGRAPHY
1. K. Park. Textbook of Preventive and Social Medicine. Genetics and health:
2011: 21:760-770
2. Sunder Lal. Textbook of Community Medicine. Medical genetics 2011: 3:
366-375
3.National Centre of Applied Human Genetics. Available from:
www.ncahg.org/vision&mission.html
4. National health profile 2010. Health Status Indicators Available from:
http://cbhidghs.nic.in/writereaddata/mainlinkFile/File1012.pdf
5. Gregor Mendel. Available from: http://en.wikipedia.org/wiki/Gregor_Mendel
6. The Basics of Gene Therapy. Available from:
http://genmed.yolasite.com/basics-of-gene-therapy.php
7. Genetic Research in India. Available from:
www.chillibreeze.com/articles_various/Genetic-Research.asp
8. Diseases and Gene Therapy - ADA-SCID. Available from:
www.bgmoedlingkeim.ac.at/fachbereiche/biologie/gentherapie/pages/krankh
eiten/krankheiten_6.html
`