GENETICS & HEALTH

Alka MishraM. 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.

2.

3.

4.

5.

6.

7.

Congenital Malformation

Down Syndrome

Metabolic Disorders

B- Thalassemia & Sickle cell disease

Congenital Hypothyroidism

Duchenne muscular dystrophy

Spinal muscular atrophy

1 : 50

1 : 800

1: 1200

1: 1700

1: 2500

1: 10,000

1: 10,000

678,000

34,000

22,500

16,700

10,900

2,700

2,700

Source : Centre of Medical Genetics, New Delhi,2011

BURDEN OF NCD IN INDIADisease Prevalence/ 1000 Cases in

millions/ yearDeaths in millions / year

Diabetes Mellitus

Ischemic Heart Disease

Stroke

Hypertension

62.4

37

1.54

159.4

37.7

22.3

1.64

94.8

0.11

0.55

0.63

-----

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

CLASSIFICATIONClassification of diseases based on their genetic basis as

• Monogenic (Mendelian) disorders• Chromosomal aberrations• Polygenic disorders

Mendelian disorders6 general patterns of inheritance are observed:• Autosomal recessive • Autosomal dominant• X-linked recessive• X-linked dominant• Co-dominant• Mitochondrial

Mendelian disordersAutosomal recessive • The disease appears in male and female children of unaffected parents. e.g., Cystic Fibrosis, Phenylketonuria

Mendelian disordersAutosomal 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 disordersX-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 disordersX-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 disordersCo-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 disordersMitochondrial 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, Trisomy21, fragile X,

Hemophillia

DM, HT, Heart disease, obesity,

schizophrenia, Asthma

RSA, TB, Struck by lightening,

Meningococcal 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 • Previous child with a

chromosome abnormality• Family history of a

chromosome abnormality• Family history of single

gene disorder• Family history of neural

tube defect (NTD)

•Family history of other congenital structural abnormalities•Abnormalities identified in pregnancy•Other high risk factors (consanguinity, poor obstetric history, maternal illnesses)

Prenatal screening for genetic disorders

• Invasive testing:

− Amniocentesis− Chorionic villus

sampling (CVS)− Cordocentesis− Preimplatation genetic

diagnosis− Fetoscopy

• Non-invasive testing:

− Ultrasonography− Maternal serum AFP− Isolation of foetal cells

from maternal circulation

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

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www.ncahg.org/vision&mission.html4. National health profile 2010. Health Status Indicators Available from:

http://cbhidghs.nic.in/writereaddata/mainlinkFile/File1012.pdf5. Gregor Mendel. Available from: http://en.wikipedia.org/wiki/Gregor_Mendel6. The Basics of Gene Therapy. Available from: http://genmed.yolasite.com/basics-

of-gene-therapy.php7. Genetic Research in India. Available from:

www.chillibreeze.com/articles_various/Genetic-Research.asp8. Diseases and Gene Therapy - ADA-SCID. Available from:

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