Genetics and health

1. GENETICS AND HEALTH
Dr Jazeela Mohamed Siddique
Senior resident
Department Of Community Medicine

2. Introduction
• Human genetics for understanding
• the endogenous factors in health and disease and
• the complex interaction between the nature and nurture
• Effective medical and preventive intervention in many diseases
• Genetic engineering – controlling traits of individuals

3. Chromosomes
• Chromatin coiled in form of rod like structures called chromosomes in nucleus of
human cells
• Chromosomes – made of DNA
• Each chromosome contain genes in a linear order
• Genes are codes for cells to make proteins
• Alteration in genes or chromosomes alter the protein produced
• 23 pair chromosomes  1 – 22 pairs are autosomes ; 23rd pair – sex chromosome
• Somatic cells – diploid (23 pairs) ; Germ cells – haploid (23 )

4. Genes
• Genes allele pair are alike (AA) – homozygous; allele different (Aa) – heterozygous
• Dominant gene – manifest effect in homozygous and heterozygous state
• Recessive gene – manifest effect only in homozygous state
• Genes whose combined action affects one particular character – POLYGENES
Eg : Muscular dystrophy, colour of skin, height & weight, life span
• The extent to which a genetically determined condition is expressed in an individual
– Penetrance
• Mutation – normal genes converted into abnormal ones

5. Chromosomal abnormalities
• Non disjunction
• Translocation
• Deletion
• Duplication
• Inversion
• Isochromosomes
• Mosaicism

6. Laws of inheritance
Two alleles of the same gene
come from different gametes
Law of segregation Law of dominance
When two different alleles are
present, only one is dominant
and will be expressed
Law of unit characters
A hereditary trait is carried by a
pair of genes

7. Genetic
disorders
Chromosomal
diseases
Sex chromosome
disorders
Autosomal disorders
Mendelian
diseases
Autosomal dominant
traits
Autosomal recessive
traits
Recessive sex linked traits
Dominant X linked traits
Multifactorial
diseases
Classification

8. Sex chromosome disorders
Klinefelter’s syndrome
• Aneuploidy
• Abnormal males XXY, XXXY
• Eunuchoid males with non-functional
testis, spermatozoa absent in ejaculate
• Scanty hair growth on face, axilla, pubis
• Gynaecomastia and mental retardation
XYY syndrome
• Male with extra Y chromosome
• Anti-social, aggressive, criminal
behaviour
• Height ≥ 6 feet
• Personality disorder  behavioural
disturbances

9. Turner’s syndrome
• Apparent females with underdeveloped
sex glands
• 45 X0  non-disjunction of sex
chromosomes
• Short stature, infertile, primary
amenorrhoea
• Coarctation of aorta, pulmonary stenosis,
renal malformations, mental retardation
Super females
• XXX, XXXX, XXXXX
• Higher the number X chromosomes –
higher degree of mental retardation
and congenital anomalies
• Underdeveloped external genitalia,
uterus and vagina

10. Autosomal disorders
• Mongolism or Down syndrome - Trisomy 21
• Short stature, small round head, narrow tilted eye slits, malformed
ears, short broad hands, lax limbs, mental retardation
• Congenital - cardiac defects, atresia of alimentary tract
• Frequency of mongolism rises with increasing maternal age

11. Mendelian diseases

12. Autosomal dominant traits Achondroplasia
Huntington’s chorea
Neurofibromatosis
Familial Polyposis coli
Brachydactylia
Marfan’s syndrome
Retinoblastoma
ABO blood group system
Hyperlipoproteinemia I, II, III, IV
Polycystic kidney disease
Polydactyly
Hereditary spherocytosis
Autosomal recessive traits Fibrocystic disease of the pancreas
Phenylketonuria, Alkaptonuria
Albinism
Tay Sachs disease
Agammaglobulinemia – Swiss type
Haemoglobinopathies
Cystic fibrosis
Galactosemia
Maple syrup urine disease
Hirschsprung’s disease

13. Recessive sex linked traits Haemophilia A & B
Duchenne muscular dystrophy
Colour blindness
G6PD deficiency
Hydrocephalus
Retinitis pigmentosa
Agammaglobulinemia – Bruton type
Dominant X linked traits Vit D resistant rickets
Familial hypophosphatemia
Blood group Xg
Blood group Disease
O • Duodenal ulcer, Gastric ulcer
• Hemolytic tendencies
A • Stomach cancer, Uterus & cervical cancer, pernicious anaemia
• Thrombosis

14. Erythroblastosis foetalis
• Rh positive foetus in Rh negative mother
• Foetal red cells cross the placenta  enter maternal circulation
• Foreign antigen  Rh antibody production
• Rh antibody – 2 types
1. Strong or saline antibodies
2. Weak or albumin antibodies  cross the placental barrier  pass back into
foetal circulation  foetal RBCs destroyed  death in utero (or) born with
jaundice, anaemia and oedema

15. Sickle cell anaemia
• Autosomal recessive disorder – abnormal hemoglobin
• Point mutation in DNA
• Heterozygous individuals  clinically healthy
• Homozygous suffer from acute hemolytic anaemia – die before puberty (organ failure)
• Rate of sickling depends on concentration of HbS in RBC
• Disorder onset in 1st year of life when HbF falls
• Delayed puberty, chronically ill, jaundice, hepatomegaly, enlarged heart
• No specific treatment
• Prenatal diagnosis and genetic counselling for couples at risk

16. Thalassemia
• Reduction in the synthesis of globin chain (α or β) reduced Hb synthesis
• Hypochromic microcytic anaemia
• α thalassemia – gene deletion
• Β thalassemia – point mutations
• Signs develop after 6 month when Hb synthesis shifts from HbF to HbA
• Pre natal diagnosis for at risk couple

17. Hemophilia
• Affects males, carrier females
• Deficient function of blood coagulating factor
 prolonged bleeding in large joints
• Progressive joint disease and muscle atrophy
Cystic fibrosis
• Gene defect affecting respiratory and GI tracts
and sweat glands
• Treatment – Gene therapy
Phenylketonuria
• Deficiency of liver enzyme phenylalanine
hydroxylase
• Phenylpyruvic acid in urine
• Phenylalanine accumulates in blood and tissues
 toxic effect on brainmental retardation
• Elevated blood levels of phenylalanine
• Bottle fed infants tested after 1st successful
formula (>48 hours)
• Breast fed infants tested after 7 days

18. Multifactorial disorders (Polygenetic inheritance)
• Controlled by a number of genes located at different sites
• Mode of inheritance is complex – because environmental factors are also
involved
• Eg : Diabetes, Hypertension, ischemic heart disease
• Genetic predisposition
• Premature onset of common diseases of adult life such as cancer, coronary
heart disease, diabetes, hypertension and mental disorders
• Family oriented approach with appropriate therapies

19. Advances in Molecular Genetics
• DNA technology
• Gene therapy
• Human genome project
• Human genome diversity project

20. Gene therapy
• Introduction of a gene sequence into a cell
with the aim of modifying the cell’s behaviour
into a clinically relevant fashion
• Gene introduced using
 virus (retrovirus or adenovirus) or
lipid or receptor targeting
• Inserting a gene into patient’s cell  can
become alongside other treatments in future

21. Gene therapy in Severe Combined Immunodeficiency (SCID)
Approaches to gene therapy
• In-vivo gene therapy – normal genes
are delivered inside the body
• Ex-vivo gene therapy – genes are
inserted in the cells outside the body
Cystic fibrosis
Hemophilia
Muscular dystrophy
Sickle cell anemia

22. Human Genome Project
• systematise the research on mapping and
isolating human genes, in order to create
a single linear map of the human
genome, with each coding gene defined
and sequenced
• Aimed to determine complete sequence
of nucleotide base pairs that makes up
human DNA and all gene it contains
• Coordinating HGP data – UNESCO,
Genome Data Base, HUGO, National
Institute of Health/ Department of Energy
(USA), Medical Research Council (UK),
Genethon (France) and European Union
• Started in 1990, 13 year project
• By April 2023, 92.1% completed

23. Hardy Weinberg Equilibrium
• Allele and genotype frequencies in a
population will remain constant from
generation to generation in the absence of
other evolutionary influences
• Population genetics – study of precise
genetic composition of population and
various factors determining the incidence
of inherited traits in them
Factors influencing human gene pool
• Mutation
• Natural selection
• Population movements
• Breeding structure

24. Preventive and Social Measures
• Primary prevention
• Health promotion
• Specific protection
• Secondary prevention
• Early diagnosis and treatment
• Tertiary prevention
• Disability limitation
• Rehabilitation

25. Health promotion
• Eugenics
• Euthenics
• Genetic counselling
• Other genetic preventive measures

26. Eugenics
Positive eugenics
• Efforts aimed at increasing desirable
traits
• Examples:
• Encouraging the fit to have children
• In-vitro fertilization
• Cloning
Negative eugenics
• Efforts aimed at decreasing
undesirable traits
• Examples:
• Hitler killed the weak and defective to
improve German race
• Sterilisation – to reduce frequency of
hereditary disease and disability
• Science which aims to improve the genetic endowment of the population
• controlled breeding to increase the occurrence of desirable characteristics

27. Euthenics
• Study of improvement of human functioning and well being by improvement of
living conditions
• Environmental manipulation
• Education, controllable environment, prevention and removal of contagious
parasites, employment, housing, sanitation

28. Genetic counselling
• The practice of helping individuals and families to understand the medical,
psychological, social and reproductive implications of genetic and congenital
conditions
• Determine the facts
• Transmitting the information
• Supporting the decision

29. Prospective genetic counselling Retrospective genetic counselling
Genetic defect has not occurred yet Heriditary disease already occurred in the family
True prevention of disease Most common
Identifying heterozygous individuals for any
particular defect – screening procedures
Preventing heterozygous marriages Contraception, pregnancy termination,
sterilization
Sickle cell anaemia, Thalassemia Congenital abnormalities, mental retardation,
psychiatric illness, Inborn errors of metabolism

30. Other genetic preventive measures
• Prevent consanguineous marriages
• Avoid late marriages
• Avoid pregnancy among women >30 years

31. Specific protection
• Protection of individuals and communities from mutagens – Xrays, ionizing
radiations, chemical mutagens
• Anti-D globulin  Rh hemolytic disease

32. Early diagnosis and treatment
• Detection of genetic carriers – elevated creatine kinase in Duchenne muscular
dystrophy
• Prenatal diagnosis
• Screening of newborn infants – CDH, PKU, DMD, congenital hypothyroidism, CF
• Recognizing pre clinical cases – Type 1 diabetes, PKU, Thalassemia

33. Prenatal diagnosis
Indications Methods
Advanced maternal age
Previous child with chromosome aberration
Intrauterine growth delay
Cytogenetics
• Amniocentesis (14-16 weeks)
• Chorionic villus sampling (10-13 weeks)
Biochemical disorders Protein assay, DNA diagnosis
Congenital anomaly Sonography, foetoscopy
Screening from neural tube defects and
trisomy
Maternal serum alpha fetoprotein
Chorionic gonadotrophin

34. Disability limitation
• PKU  low phenylalanine diet
• Hemophilia, sickle cell anaemia, thalassemia – therapeutic and preventive measures
• CHD, cleft lip and palate, neural tube defects – Surgical treatment
• Teaching skills through aids
• Ashwasakiranam – Assistance to caregivers
Rehabilitation

35. Genetic population screening services
Type of service Conditions Preventive or screening action
Primary prevention Rh disease
Congenital rubella
Congenital malformations
Postpartum anti-D globulin
Immunization of girls
Maternal folic acid, control of
maternal DM, avoidance of
mutagens & teratogens
Antenatal screening Congenital malformations
Chromosomal abnormalities
Inherited disease
Fetal anomaly scan, αFP estimation
Maternal age and maternal serum
factor levels, family history
Carrier screening for
haemoglobinopathies, Tay Sachs
disease
Neonatal screening Congenital malformations
PKU, congenital hypothyroidism,
sickle cell disease
Examination of newborn for early
treatment
Biochemical tests for early
treatment

36. THANK YOU !!!
https://www.slideshare.net/JazeelaMohamedSiddiq