This document discusses human genetic technologies and their implications for preventative healthcare. It begins with definitions of key genetic terms and branches of genetics. It then covers advances in genetic technologies like genetic epidemiology, molecular genetics techniques such as DNA sequencing and recombinant DNA, and applications like genetic testing and gene therapy. Population genetics concepts are explained, and the roles of genetics in public health and disease prediction are discussed. The document also examines ethical, legal and social implications of genetic technologies.

1. Human Genetic Technologies:
Implications for Preventive
Health Care
Dr. Aparna Sen Chaudhary

2. Contents
 Definitions
 Genetic Epidemiology
 Genetic Technologies Application
 Advances in Molecular Genetics
 Population Genetics
 Genetic Testing: How it is Used for Healthcare
 Ethical, legal and social implications
 Preventive and social measures
 Inadequacy of Genetics Services
 Personalized Medicine, Metagenomics, NIPT Test 02-02-2018
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3. Definitions
Genetics
Branch of science that deals with the study of
hereditary
Human Genetics
Basic biological science for understanding the
endogenous factors in health and disease and
the complex interaction between nature and
nurture.
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4. Branches in Genetics
Cytogenetics
Biochemical Genetics
Clinical Genetics
Pharmacogenetics
Immunogenetic
Microbial Genetics
Population Genetics
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5. Genetic Epidemiology
It represents a hybrid of epidemiologic
designs and statistical models that explicitly
consider both genetic and environmental risk
factors for complex disease, that is, those
disease that have some genetic components
to their aetiology but are not exclusively
Mendelian.
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6. Eras in Genetic Epidemiology
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7. Genetic factors and disease aetiology
 According to the degree of gene mutation,
diseases are categorised into the following:
1. Chromosomal diseases
2. Unifactorial disorders
3. Multifactorial disorders
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8. 02-02-2018
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Source : Pradhan S, Sengupta M, Dutta A, Bhattacharyya K, Bag S.K, Dutta C, etal. Indian genetic disease database. Nucleic Acids Research. 2011;39:D933–8

9. Chromosomal disorders
300 numerical and structural types of
chromosomal aberrations have been described
The incidence – 5.6 per 1000 live births
2 per 1000 live births represent sex aneuploids
1.7 per 1000 live births autosomal aneuploidies
1.9 per 1000 live births chromosomal
translocations
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10. Chromosomal disorders
1. Related to Sex Chromosomes
a) Klinefelter’s Syndrome (XXY, XXXY)
• Frequency is 1 in 400 among males at birth
b) XYY Syndrome
• Frequency is 1 in 1000 males at birth
c) Turner’s Syndrome (XO)
• Frequency is 1 in 3000 live girls at the birth
d) Super Female (XXX, XXXX, XXXXX)
• Frequency is 1 in 1000
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Source : Gender and Genetics. Available at: http://www.who.int/genomics/gender/en/index1.html

11. Chromosomal disorders
2. Relating to Autosomes
a) Down Syndrome
• Incidence between 1 in 1000 to 1 in 1100 live
births
• India incidence is 1.4/1000 live births
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Source:
1. Gender and Genetics. Available at: http://www.who.int/genomics/gender/en/index1.html
2. Sharma R. Birth defects in India: Hidden truth, need for urgent attention. Indian J Hum Genet. 2013; 19(2): 125–9.

12. Unifactorial (Monogenic) disorders
1. Autosomal Dominant Disease • Huntington’s chorea,
• Marfan’s syndrome,
• Retinoblastoma,
• Polycystic Kidney
2. Autosomal Recessive Disease • Phenylketonuria
• Cystic fibrosis
• Alkaptonuria
• Hemoglobinopathies
3. Sex – linked Dominant Disease • Vitamin D resistant Rickets
• Familial hypophosphatemia
4. Sex- linked Recessive Disease • Haemophilia
• G6PD Deficiency
• Colour blindness
• Retinitis Pigmentosa
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13. Multifactorial (Polygenic) disorders
Campbell (1965) stressed that environmental
factors and genetic interact closely resulting in
abnormalities.
The frequency is high compared with that of
Mendelian and chromosomal disorders.
Examples include:
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• Essential Hypertension • Diabetes
• Ischemic Heart Disease • Schizophrenia
• Congenital Heart Disease • Mental Retardation

14. Genetic Technologies Application
There are three main categories of the application of
genetic technologies:
1. Human Cloning:
 Creation of either human embryos or human
children that are genetically identical to their living
or dead parents.
2. Genetic Trait Selection:
 Selection of sperm, eggs or embryos that possess
genes which are associated with certain traits
3. Genetic modification:
 Changes and manipulation of genes in living human
cells 02-02-2018
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15. Advances in Molecular Genetics
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16. Advances in Molecular Genetics
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What we KNEW
• Structure of DNA
• Genes code for
proteins
• Human genes were
cloned
• DNA sequencing was
just being developed.
What we KNOW
• Entire Human
Genome
• Using large-scale
approaches like
genome wide
association (GWA)
• Discover new roles
for RNA
• Genetic tools like
DNA fingerprinting.
Hope to LEARN
• Use genetic
information to tailor
drug prescriptions,
screening tests, and
lifestyle
recommendations
• Predict and prevent
the emergence and
spread of infectious
diseases

17. Advances in Molecular Genetics
DNA Technology
• Synthesis of DNA probes with specific sequences
identifying complementary DNA sequences – allow
genetic diagnosis and further analysis
• DNA sequencing – rapid analysis of unknown DNA and
identification of mutation
• PCR – amplifying known DNA sequence
• Coding sequences – production of therapeutic agents
(insulin, erythropoietin, factor VIII)
• Positional cloning strategies – simplified the study of
families.
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18. Advances in Molecular Genetics
DNA Technology
• In Vitro – examining protein product of gene sequences
with unknown function
• Fluorescence in situ hybridization (FISH) – permits direct
visualization of genes to one another
• Comparison between DNA sequences- elucidate
mechanism of evolution
• Insertion of coding DNA sequences into animal embryos
– create transgenic animals.
• Insertion of missing DNA or excision of harmful one
(GENE THERAPY)
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19. Advances in Molecular Genetics
Recombinant DNA Technology
When two DNAs of different origin are combined, the
result is a recombinant DNA molecule.
The recombinant DNA molecule is placed in a host cell.
The host cell then replicates (producing a clone), and
following its amplification it can be purified for further
analysis.
The top four applications are:
a) Diagnosis of Genetic Diseases
b) DNA Typing
c) Gene Therapy
d) Synthesis of Human Insulin and Hepatitis B Vaccine
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20. Advances in Molecular Genetics
Gene Therapy
Introduction of a gene sequence into a cell
Aim of modifying the cell’s behaviour
Gene may be introduced using virus (retrovirus or
adenovirus) or by means of lipid or receptor targeting.
Used –
• Genetic mutation – Cystic Fibrosis
• Kill a cell – Cancer
• Modify susceptibility – Coronary Heart Disease
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21. Advances in Molecular Genetics
The Human Genome Project
Is an attempt to systematize the research on
mapping and isolating human genes that is
already in progress in many countries.
Agencies include UNESCO, the Genome Data
Base, HUGO, the National Institute of
Health/Department of Energy (USA), the Medical
Research Council (UK), Genethon (France) and
the European Union.
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22. 02-02-2018

23. Advances in Molecular Genetics
The Human Genome diversity project
Is aimed at increasing understanding of Human
evolution
Major objective – define the genetic relationships
between human population and interpret them.
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Source: The Human Genome Diversity Project: past, present and future (2005)

25. Population Genetics
Defined as a study of the precise genetic
composition of population and various factors
determining the incidence of inherited traits in
them.
Founded by Hardy in England and Weinberg in
Germany in 1908.
Hardy – Weinberg Law states “the relative
frequencies of each gene allele tends to remains
constant from generation to generation.”
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26. Population Genetics
Factors influencing Gene Frequency
a) Mutations
b) Natural Selection
c) Population Movements
d) Breeding Structure
e) Public Health Measures
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27. Role of Genetics in Public Health
Identification of a genetic condition or
predisposition before the onset of clinically
recognized, irreversible disease.
Evidence that screening for a genetic trait and
providing early intervention results in improved
prognosis and favourable health outcomes.
Helps in identification and modification of
environment risk factors among persons
susceptible to disease due to genotype.
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28. Population targeted by Public Health
Genetics Intervention
Priorities need to be established
Depends on the burden of these rare diseases
Ethnic group can be target population of
screening programs
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29. Genetic Predisposition in Human Disease
Genetic predisposition in human disease can
help accomplish goals of Public Health
1. Improved prediction of individuals at risk
2. Design and implementation of targeted
biologic interventions
3. Deeper insights into biology of a disease
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30. Genetic Testing: How it is Used for
Healthcare
 Yesterday
a) Late 1800s - Chromosomes first discovered
b) Early 1900s - inherited diseases were first linked to
chromosomes.
c) 1950s - Genetic tests for genetic conditions such as
Down syndrome, cystic fibrosis, and Duchenne
muscular dystrophy.
d) Genetic testing was used to confirm a diagnosis of a
genetic condition, and to screen new-borns for
conditions such as phenylketonuria (PKU).
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31. Genetic Testing: How it is Used for
Healthcare
 Today
a) Genetic testing is available for over 2000 rare and
common conditions.
b) There are a number of different types of genetic tests
available today
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1. Diagnostic testing 5. Pre-implantation testing
2. Predictive and pre-
symptomatic testing
6. New-born testing
3. Carrier testing 7. Research genetic testing
4. Prenatal testing 8. Pharmacogenetics testing

32. Genetic Testing: How it is Used for
Healthcare
 Tomorrow
a) Genetic Test Registry
b) Cost of genetic testing to decline. Eventually the
cost of sequencing an individual’s entire genome
- will be less than $1,000.
c) Time of more effective “Personalized Medicine”.
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33. Ethical, legal and social implications
1. Use of genetic information: confidentiality and
discrimination
a) Genetic information does not change over time
b) Genetic information about one individual has
implications not only for the individual but also
for his/her family members.
c) Information might be used as a source of
discrimination
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35. Ethical, legal and social implications
2. DNA Banks
a) Many DNA banks were formed from DNA samples
collected for specific research or projects
b) Once they serve their use…. WHAT SHOULD NOW
BE DONE WITH THESE SAMPLES?CAN THE
RESEARCHERS USE THEM WITHOUT THE CONSENT
OF THOSE WHO GAVE THE SAMPLES? Etc.
c) Researchers and ethicists face such issues because
nature of prospective research will depend on
decision to use the sample from DNA bank or not.
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37. Ethical, legal and social implications
3. Prenatal diagnosis, assisted reproduction and
embryo selection
a) Genetic test performed make it possible to select
only embryos that fit certain criteria.
b) For now, it is use to avoid birth of children with
severe hereditary disorders.
c) It might open the door to “Embryo selection”
d) Prenatal diagnosis implies that selective abortion is
an option
e) It raises the question of legal status of embryo. 02-02-2018
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38. Ways to address privacy concerns
• UNESCO Bioethics Committee and International
Regulation of Gene Therapy, 1994
• Genetic Information Non-discrimination Act GINA,
US;2008
• Gene Technology Act 2000
• Genetic Engineering Appraisal Committee (GEAC), 1989
• Recombinant DNA Safety Guidelines, 1990 & 1994
• Guidelines for Generating Preclinical and Clinical Data for
rDNA vaccine, 1989
• The Biotechnology Regulatory Authority of India Bill, 2013
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INDIAN GUIDELINES

39. Preventive and social measures
Health Promotional Measures
1. Eugenics
a) Proposed by GALTON
b) Aim – to improve the genetic endowment of
human population
c) Can be
I. Negative Eugenics
II. Positive Eugenics
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40. Preventive and social measures
Health Promotional Measures
2. Euthenics
a) This consist of improving the quality of
human environment, since it has influence on
the genetic potential/development.
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41. Preventive and social measures
Health Promotional Measures
3. Genetic Counselling
a) Process of offering advice to the individuals
to improve the genetic constitution at the
individual family level.
b) Two types
I. Prospective Counselling
II. Retrospective Counselling
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42. Preventive and social measures
Health Promotional Measures
4. Other General Measures
a) Prevention of Consanguineous Marriage
(prevents albinism, alkaptonuria,
phenylketonuria)
b) Avoiding Late Marriages (prevents Down’s
Syndrome)
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43. Preventive and social measures
Specific Measure
a) Avoiding exposure to mutagens (radiation,
chemicals)
b) Immunization against Rubella
c) Immunization of Rh-ve mothers with anti D-globulin
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44. Preventive and social measures
Early Diagnosis and Treatment
a) Detection of Genetic Carriers
b) Prenatal Diagnosis
i. USG
ii. Amniocentesis
iii. Chorionic Villous Sampling
c) Neonatal Screening Procedures
i. Clinical and Biochemical Examination
ii. Hb Electrophoresis
d) General population screening procedures 02-02-2018
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45. Preventive and social measures
Indication for Prenatal
Diagnosis
Methods
I. Advanced maternal age,
previous child with
chromosome aberration,
intrauterine growth delay
Cytogenetic (Amniocentesis,
Chorionic villous sampling)
2. Biochemical disorders Protein assay, DNA diagnosis
3. Congenital anomalies Sonography, foetoscopy
4. Screening for neural tube
defects and trisomy
Maternal serum Alpha-feto
protein and chorionic
gonadotropin 02-02-2018
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46. Preventive and social measures
Disease Treatment
• Phenylketonuria Diet low in phenylalanine
• Hemophilia Factor VIII
• Spina Bifida Surgery
• Galactosemia Restriction of galactose
• Lactase Deficiency Restriction of Lactose
• Agammaglobulinemia Administration of Gamma Globulin
• Homocystinuria Administration of Pyridoxine
• Maple syrup urine disease Administration of Thiamine
• Hereditary spherocytosis Splenectomy
• Familial polyposis of colon Colectomy
• Adult polycystic kidney disease Kidney Transplantation
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47. Established Genetic population-screening services
Type of service Conditions Preventive or screening action
Primary
Prevention
• Rhesus haemolytic disease
• Congenital rubella
• Congenital malformation
Postpartum use of Anti- D globulin
Immunization of girls
Folic acid, control maternal
diabetes, avoidance of mutagens
Antenatal
screening
• Congenital malformations
• Chromosomal
abnormalities
• Inherited disease
USG of Foetal anomaly scan,
maternal serum AFP estimation
Maternal age and maternal serum
factor levels
Carrier screening
Neonatal
screening
• Congenital malformations
• Phenylketonuria, sickle cell
anemia
Examination of new-born for early
treatment
Biochemical test for early
treatment 02-02-2018
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48. Inadequacy of Genetics Services
Paucity of Resources
Unaddressed needs in areas of Health Care
Presence of other competing priorities
Low genetic literacy among general public
Culture, legal or religious limitations
Insufficient number of trained health professionals
Inadequate data on health and economic burden
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49. Personalized Medicine
It is the practice of sequencing a patient’s genome
and combining this information with new
knowledge of genetic basis of many disease, as
well as the genetic component of treatment.
The Personalized Medicine Coalition, an
independent, non-profit group “works to advance
the understanding and adoption of personalized
medicine for ultimate benefit of patients”.
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50. Personalized Medicine…
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Advantages
a) Pharmacogenomics
b) Reduce inappropriate
prescriptions
c) Personalized health
and nutritional
recommendations.
E.g. SCIONA
Disadvantages
a) Possibility of
unauthorized or even
discriminatory use of the
information
b) Genomic information of
one person can imply to
genetic makeup of the
blood relatives, raising
privacy issues.

51. Metagenomics
 Metagenomics to envision medical microbiology from
ecological viewpoint.
 It skips the step of culturing and isolating individual
microbes and leaps to the step of sequencing the DNA
isolated directly from an investigational microbial
community.
 Leading to the revolutionary era of designing probiotics
which serve as a new approach to disease prevention
and treatment (Regenerative medicine).
 Lactobacillus reuteri 30242 has been found to lower
cholesterol. 02-02-2018
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52. NIPT Test/ Harmony Test/ Panorama Test
 Non invasive Prenatal Testing to detect chromosomal
abnormalities
 Maternal blood carries call free foetal DNA which can be
isolated and measured
 Accuracy – 99.5%
 Done typically between 10th – 24th week of gestation
 Recommended among
Maternal age above 35 years
Family history
Any abnormal Prenatal Test 02-02-2018
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53. Central Research Lab
KMC, Manipal

54. • Malformation Syndromes • Primary amenorrhea
• Chromosomal abnormalities (Down
syndrome, Turners Syndrome)
• Advanced maternal age (>35 years)
• Genetic anaemic (Thalassemia) • Infertility
• Mental retardation/ developmental delay • Exposure to teratogens during pregnancy
• Short stature • Familial cancers
• Skeletal dysplasia • Any familial / genetic disorder
• Myopathies • Neurodegenerative disorders
• Inborn errors of metabolism • Ambiguous genitalia
• Deafness • Genetic bleeding disorders
• Neural tube defects
• Clinical services offered (Evaluation, Diagnosis,
Counseling, Management and Prenatal Diagnosis)

55. • Laboratory facilities
1. Karyotyping from blood, tissues, chorionic villi, amniotic fluid and
products of conception
2. Quantitative fluorescent PCR (QF-PCR) for rapid detection of
aneuploidy in prenatal samples
3. Molecular diagnostic services and prenatal diagnosis for genetic
disorders
4. Biochemical testing for inborn errors of metabolism

56. Prenatal diagnosis and genetic counselling
1.Scanning for fetal malformations by ultrasound
2.Chorionic villus sampling
3.Amniocentesis
Fetal autopsy
In case of stillbirths and foetuses aborted after ultra sonographic detection of
malformations, detailed radiologic study and autopsy helps in providing a definitive
diagnosis of the condition.

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58. References
• Fallin MD, Duggal P, Beaty TH. Genetic Epidemiology and Public Health: The
Evolution From Theory to Technology. American Journal of Epidemiology.
2016;183(5):387-93.
• Laberge AM. Genetics and Public Health. Atlas Genet Cytogenet Oncol
Haematol. 2004:181-90.
• Hanen M. Genetic Technologies and Medicine: Privacy, Identity, and
Informed Consent. Available at :
https://www.idtrail.org/files/ID%20Trail%20Book/9780195372472_kerr_10
.pdf
• Brand A, Brand H, Baumen TS. The impact of genetics and genomics on
public health. European Journal of Human Genetics. 2008;16:5-13.
• Pradhan S, Sengupta M, Dutta A, Bhattacharyya K, Bag S.K, Dutta C, etal.
Indian genetic disease database. Nucleic Acids Research. 2011;39:D933–8.
• Kar SK. The Human Microbiome Concept of Disease Prevention and
Treatment: A Giant Leap in Medical Genetics. Hereditary Genet. 2016;5:1.
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59. References
• FACT SHEET - Genes: What We Knew, Know, and Hope to Learn National
Institutes of Health. 2010
• Fact Sheet - Genetic Testing: How it is Used for Healthcare National
Institutes of Health. 2010
• Gender and Genetics. Available at:
http://www.who.int/genomics/gender/en/index1.html
• Sharma R. Birth defects in India: Hidden truth, need for urgent attention.
Indian J Hum Genet. 2013; 19(2): 125–9.
• Suryakantha AH. Community Medicine with Recent Advances. 4th Edition.
New Delhi: Jaypee Brothers;2017
• Park K. Textbook of Preventive and Social Medicine. 23rd Edition. Jabalpur:
Bhanot Publishers ;2017
• Ali M A. Genetic Technologies and Ethics. J Med Ethics Hist Med. 2009; 2:
11.
• Fact Sheet - Human Genome Project National Institutes of Health.2010. 02-02-2018
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