genetics

1. GENETICS AND HEALTH
PRESENTED BY-NISHAYADAV
MSC NURSING 1ST YEAR
NINE, PGIMER,
CHANDIGARH

2. OUTLINE
• Basic concepts related to genetics- DNA, genes, chromosomes, cell
division, laws of inheritance, mutation
• Genetic disorders- chromosomal disorders, mendelian diseases
• Advances in molecular genetics- DNA technology, gene therapy,
human genome project, human genome diversity project
• Preventive and social measures- health promotion, early diagnosis
and treatment, rehabilitation
• Practical application of genetics in nursing
• Summary
• Conclusion
• References

3. BASIC CONCEPTS RELATED TO
GENETICS
• Genetics- definition, branches, history
• Cytological facts
• DNA
• Gene
• Chromosome- definition and
methods of chromosomal study
• Cell division- mitosis and meiosis
• Genotype and phenotype
• Laws of inheritance
• Mutation- definition, types

4. GENETICS
DEFINITION-
The science that deals with the study of heredity and variations is known as genetics.
BRANCHES OF GENETICS-
There are broadly 3 branches of genetics:
– Cytogenetics - The field which gives knowledge of structure of nucleus of cell and its parts, i.e.
chromosomes. Thus normal and abnormal chromosomes can be studied.
– Molecular genetics - The field dealing with the molecular structure of genetic material, i.e. DNA.
– Biochemical genetics - The field deals with the biochemistry of genetic material for normal
metabolic processes.

5. HISTORY OF GENETICS
 The concept of genetics dates back to 6000 years as evidenced in the stone
engravings from Chaldea in Babylonia in current Iraq these engravings depict
pedigrees relating to some characteristics in horses.
 As regards human heredity, hemophilia was the first genetic disorder known
about 1500 years ago
 In 1866: Gregor Mendel an Austrian monk who is usually considered “father of
genetics” advanced the field significantly by performing a series of cleverly
designed experiments on living organisms.
 He then used this experimental information to formulate a series of fundamental
principles of heredity
 1869: Friedrich Miescher identified DNA

6. o1900-1913:
 Chromosomal theory of inheritance : Sutton and
boveri
 Genes on chromosomes: TH Morgan
 Genes linearly arranged on chromosomes and
mapped- AH Sturtevant
o1941- George Beadle and Ed Tatum related gene to enzyme
and biochemical processes
o1944- Oswald Avery demonstrated that DNA was genetic
material

7. CYTOLOGICAL FACTS
• In 1956, Tjio and Levan found 46 chromosomes in the normal human karyotype
• Barr discovered that normal female cell nucleus contains a dark staining area at
periphery called as Barr body or sex chromatin which is not present in males
• The autosomes have been classified and divided on basis of length and certain
morphological similarities into 7 groups-
– Group A- 1 TO 3 pairs
– Group B- 4 and 5 pairs
– Group C- 6 to 12 pairs
– Group D- 13 to 15 pairs
– Group e- 16 to 18 pairs
– Group F- 19 and 20 pairs
– Group G- 21 and 2 pairs
• The X chromosome is included in group C with chromosomes 6-12 and the Y
chromosome is included in Group G with chromosome 21 and 22

8. STRUCTURE OF POLYNUCLEOTIDE CHAIN
 A nucleotide has three components— a nitrogenous base, a pentose sugar, and a
phosphate group. There are two types of nitrogenous bases– Purines and Pyrimidines.
 Purines – Adenine and Guanine.
 Pyrimidines – Cytosine, Uracil and Thymine.
 A nitrogenous base is linked to the pentose sugar through a N-glycosidic linkage to
form a nucleoside.
 When phosphate group is linked to 5’-OH of a nucleoside through phosphoester
linkage, corresponding nucleotide is formed. Two nucleotides are linked through 3’-
5’phosphodiester linkage to form dinucleotide.
 A polymer thus formed has at one end a free phosphate moiety at 5’-end of ribose
sugar, which is referred to as 5’ -end of polynucleotide chain.

 Similarly, at the other end of the polymer the ribose has a free 3’ -OH group which is
referred to as 3’-end of the polynucleotide chain.

9. DNA

10. DNA

11. WATSON AND CRICK DNA DOUBLE
HELIX MODEL
• In 1953, James Watson and Francis Crick gave his famous double helix model of
structure of DNA, based on the x-ray diffraction data produced by Maurice Wilkins
and Rosalind franklin.
• This proposition was based on the observation of Erwin Chargaff that for a double
stranded DNA, the ratio between adenine and thymine and guanine and cytosine are
constant and equal (A+G=T+C; A=T and G=C)

12. SALIENT FEATURES OF MODEL
 It is made of two polynucleotide chains, where the backbone is constituted by sugar-
phosphate, and bases project inside.
The two chains have antiparallel polarity. It means, if one chain has the polarity 5’-3’,the
other has 3’-5’.
 The bases in two strands are paired through hydrogen bond (H-bonds) forming base
pairs {bp}. Adenine forms two hydrogen bonds with Thymine from opposite strand
and vice versa. Similarly, Guanine is bonded with Cytosine with three H-bonds. As a
result, always a purine comes opposite to pyrimidine. This generates approximately
uniform distance between the two strands of the helix.
The two chains are coiled in a right-handed fashion. The pitch of the helix is 3.4 nm
and there are roughly 10 bp in each turn. Consequently, the distance between a bp in a
helix is approximately equal to 0.34 nm.
The plane of one base pair stacks over the other in double helix. This, in addition to H-
bonds, confers stability of the helical structure.

14. GENE
 Gene term was coined by W Johansen in 1909.
 E R Garrod(1908) proposed one gene-one product
hypothesis.
 Gene theory was proposed by T H Morgan in 1911.
 The first structure of gene was given by Seymour
Benzere(1962).
 Gene concept was given by Sutton.

15. Morgan's Concept of the Gene (Classical Concept)
• TH Morgan (1910) proposed that the genes are arranged on a chromosome in a linear
sequence like beads on a string. Each gene occupies a specific place called its “locus”. It
the basic unit of structure which is not subdivisible by recombination and is the smallest
unit of genetic material capable of independent mutation. Thus, Morgan regarded the
gene as the unit of function and the unit of structure defined by recombination and
mutation.
Modern Molecular Concept of the Gene
• According to the current molecular concept, the gene is the unit of function, the unit of
inheritance coding for one polypeptide chain. Structurally, it consists of a segment of
molecule having a specific sequence of nucleotide.
•
• DNA is a long polymer of deoxyribonucleotides. The length of DNA is usually defined
a number of nucleotides present in it. This also is the characteristic of an organism.

16. CHARACTERISTICS OF GENES
• Genes are the units of heredity. They contain the hereditary information encoded in
their chemical structure for transmission from generation to generation.
• Genes also occur in pairs. If the genes comprising a pair are alike(AA), the individual is
described as homozygous for that gene, and if it is different (Aa) the individual is
described as heterozygous.
• A gene is said to be dominant when it manifest its effect both in the heterozygous and
the homozygous state
• A gene is said to be recessive when it manifest its effect only in the homozygous state
• Gene whose combined action affects one particular character are known as polygenes
or multiple genes.
• Genes are usually stable but sometimes normal genes may be converted into abnormal
ones- this change is called as mutation.

17. GENOTYPE AND PHENOTYPE
• The term Genotype refers to the total genetic constitution of an
individual
• Phenotype refers to the outward expression of the genetic constitution
• For e.g. In ABO blood group system
Genotype- AA, AB, BB, AO, BO, OO
Phenotype- A, B, O
• There are two aspects of the genetic material- one fixed and the other
one is plastic.
• Fixed characters are the genotype and the plastic ones are the
phenotype.

18. CHROMOSOMES
Chromosomes are rod-like condensations of chromatin. They
become visible in the nucleus only during cell division. They
occur in pairs - one member of each pair comes from the
father, and other from the mother.

19. METHODS OF STUDYING THE
CHROMOSOMES
Process of karyotyping:
• The cells which divide rapidly in culture medium are used. The most commonly used cells are
of skin, bone marrow cells and peripheral blood lymphocytes and even exfoliated amniotic fluid cells
from a pregnant woman.
• Viable cells can also be obtained within few hours of death of individual or following abortion. From
peripheral blood, the lymphocytes are separated and added to a culture medium with
phytohemagglutinin added to it.
• This stimulates the leukocytes to divide. The cells are cultured under aseptic measures at 37 degree
Celsius (C) for about 3 days; the cell division is arrested by adding a small amount of colchicine to the
culture.
• After one hour of adding colchicine, a hypnotic solution is added to swell the cells and allow the
chromosomes to spread on the slide. Now a high powered photomicrograph is taken and each
chromosome is cut-out from photograph, arranged in pairs in decreasing order of size and numbered
22 and two sex chromosomes indicated separately, forming a karyotype.
• The whole process is called karyotyping. The karyotyping will tell only the number and gross features
chromosomes but it is difficult to detect the structural abnormalities of chromosomes, however minor
may be.

20. CELL DIVISION
Why Do Cells Divide?
 Cells divide for many reasons. Cells also divide so living things can grow. When
organisms grow, it isn't because cells are getting larger. Organisms grow
because cells are dividing to produce more and more cells. In human bodies,
nearly two trillion cells divide every day.
 In cell division, the cell that is dividing is called the "parent" cell. The parent cell
divides into two "daughter" cells. The process then repeats in what is called the
cell cycle.
How do cells divide ?
Depending on the type of cell, there are two ways cells divide—mitosis and
meiosis. Each of these methods of cell division has special characteristics.
 One of the key differences in mitosis is a single cell divides into two cells that
are replicas of each other and have the same number of chromosomes.

21. MITOSIS
• During ordinary cell division, each chromosome divides lengthwise into two sister
chromosomes called chromatids. The chromatids are joined together for a short
time at a point called centromere. Then the chromatids separate, one goes to one
daughter cell, and one to the other daughter cell. In this manner, each daughter cell
inherits the same number and kind of sister chromosomes. This process of nuclear
division is called as mitosis
Mitosis cell division creates two genetically identical daughter diploid cells. The major steps of
mitosis are shown here. (Image by Mysid from Science Primer and National Center for
Biotechnology Information)

22. The mitosis division process has several steps or phases of the cell cycle—interphase,
prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis—to
successfully make the new diploid cells

23. MEIOSIS
• Meiosis is cell division that creates sex cells, like female egg cells or male sperm cells. In
meiosis, each new cell contains a unique set of genetic information. After meiosis, the
sperm and egg cells can join to create a new organism.
The meiosis cell cycle has two main stages of division -- Meiosis I and Meiosis II. The end result of
meiosis is four haploid daughter cells that each contain different genetic information from each other
and the parent cell.

24. Meiosis has two cycles of cell division, conveniently called Meiosis I and Meiosis II. Meiosis I halves the number of
chromosomes and is also when crossing over happens. Meiosis II halves the amount of genetic information in each
chromosome of each cell. The end result is four daughter cells called haploid cells. Haploid cells only have one set
of chromosomes - half the number of chromosomes as the parent cell.

25. MENDEL’S LAWS OF INHERITANCE
 Gregor Mendel, conducted hybridization experiments on garden peas for seven years
(1856-1863) and proposed the laws of inheritance in living organisms. During Mendel’s
investigations into inheritance patterns it was for the first time that statistical analysis
and mathematical logic were applied to problems in biology.
 Mendel investigated characters in the garden pea plant that were manifested as two
opposing traits, e.g., tall or dwarf plants, yellow or green seeds.
 Mendel selected 14 true-breeding pea plant varieties, as pairs which were similar except
for one character with contrasting traits. Some of the contrasting traits selected were
smooth or wrinkled seeds, yellow or green seeds, smooth or inflated pods, green or
yellow pods and tall or dwarf plants.

26. Results of Mendel’s Experiments:
Results of Mendel’s experiments on crossing a pure tall pea plant with a pure short pea plant.
 In the F1 generation, Mendel observed that all plants were tall. there were no dwarf plants.
 In the F2 generation, Mendel observed that 3 of the offspring were tall whereas 1 was dwarf.
 Similar results were found when Mendel studied other characters.
 Mendel observed that in the F1 generation, the characters of only one parent appeared whereas, in the F2 generation, the
characters of the other parent also appeared.
 The characters that appear in the F1 generation are called dominant traits and those that appear for the first time in the F2
generation are called recessive traits.

27. LAWS OF INHERITANCE
• Mendel proposed three laws of inheritance:
 Law of Dominance
 The Law of Segregation
 Law of independent assortment

29. MUTATION
A mutation occurs when a DNA gene is damaged or changed in such a way as to alter
the genetic message carried by that gene.
A mutation is a permanent change in the DNA sequence of a gene. Mutation is a
gene's DNA sequence’ can alter the amino acid sequence of the protein encoded by
the gene.
Causes of Mutations
1. DNA fails to copy accurately
2. External influences can create mutations

30. Types of Mutations
• Missense mutation
• Non- sense mutation
• Silent mutation
• Splice site mutation
Single base substitution
• Frameshift mutation
Insertion and deletion
• Inversion
• Deletion
• Translocation
• Nondisjunction
• duplication
Chromosomal mutations

31. SINGLE BASE SUBSTITUTION
• Missense mutations: In a missense mutation, the new base alters a codon resulting in a
different amino acid being incorporated into the protein chain. This is what happens in sickle
cell anemia. The 17th nucleotide of the gene for the beta chain of hemoglobin is changed
from an ‘a’ to a ‘t’. This changes the codon from ‘gag’ to ‘ggt’ resulting in the 6th amino acid
of the chain being changed from glutamic acid to valine. This apparently trivial alteration to
the beta globin gene alters the quaternary structure of hemoglobin, which has a profound
influence on the physiology and well-being of the individual.

32. • Nonsense mutations: In a nonsense mutation, the new base changes a codon that specified an
amino acid into one of the stop codons (taa, tag, tga). This will cause translation of the mRNA to
stop prematurely and a truncated protein to be produced. This truncated protein will be unlikely to
function correctly. Nonsense mutations occur in between 15 to 30% of all inherited diseases
including cystic fibrosis, hemophilia, retinitis pigmentosa and duchenne muscular dystrophy.
• Silent mutations: Silent mutations are those that cause no change in the final protein
product and can only be detected by sequencing the gene. Most amino acids that make-
up a protein are encoded by several different codons. So, if for example, the third base in
the ‘cag’ codon is changed to an ‘a’ to give ‘caa’, a glutamine (Q) would still be
incorporated into the protein product, because the mutated codon still codes for the
same amino acid. These types of mutations are ‘silent’ and have no detrimental effect.

33. INSERTION AND DELETION
• Frameshift mutation- Insertions and deletions of one or two bases or multiples of one
or two cause frameshifts (shift the reading frame). These can have devastating effects
because the mRNA is translated in new groups of three nucleotides and the protein
being produced may be useless.

34. CHROMOSOMAL MUTATIONS
• Translocations: Translocations are the transfer of a piece of one chromosome to a non-
homologous chromosome. They are often reciprocal, with the two chromosomes
swapping segments with each other. In most cases of chronic myelogenous leukemia
(CML), the leukemia cells share a chromosomal abnormality known as Philadelphia
chromosome. This abnormality is the result of a reciprocal translocation between
chromosomes 9 and 22. An abnormal hybrid gene is created leading to the production of
a novel protein that is not normally found in the cell. This protein prevents normal
growth and development, leading to leukemia.

35. • Inversion: A region of DNA on the chromosome can flip its orientation with respect to
the rest of the chromosome.
• Deletions: A large section of a chromosome can be deleted resulting in the loss of a
number of genes

36. • Nondisjunction: During cell division, the chromosomes fail to successfully separate
to opposite poles, resulting in one of the daughter cells having an extra
chromosome and the other daughter cell lacking one.
• If this nondisjunction occurs in chromosome 21 of a human egg cell, a condition
called Down's syndrome (DS) occurs. A person suffering with DS has 47
chromosomes in every cell instead of the normal 46. They suffer from heart defects,
mental retardation and stunted growth. However, it must be pointed out that the
distributions of IQs of people with DS overlaps considerably with the IQ distribution
of ‘normal’ (non-DS) population, mainly due to changes in education policy in the
last 30 years.
• Duplications: In this mutation, some genes are duplicated and displayed twice on
the same chromosome.

37. GENETIC DISORDERS
 CHROMOSOMAL DISORDERS
• Klinefelter disorder
• XYY syndrome
• Turner syndrome
• Superfemales
• Down syndrome
 MENDELIAN DISORDERS

38. 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
hemoglobin disorders, mainly sickle-cell disease and thalassemia.
 Over 300 000 babies with severe hemoglobin disorders are born each year.

39. CLASSIFICATION OF GENETIC
DISORDERS
• These may be classified as:
Chromosomal abnormalities
Unifactorial/ monogenic/ Mendelian disorders
Multifactorial disorders

40. CHROMOSOMAL ABNORMALITIES
 Relating to sex chromosomes
 Klinefelter's syndrome
 XYY syndrome
 Turners syndrome
 Super females
 Relating to autosomes
 Trisomy 21
 Trisomy 18
 Trisomy 13

41. C H R O M O S O M A L D I S O R D E R S :
R E L AT I N G T O S E X C H R O M O S O M E S
• Klinefelter’s syndrome
• XYY syndrome
• Turner’s syndrome
• Superfemales

42. KLINEFELTER SYNDROME
• This is a common sex - chromosome
aneuploidy.
• Persons suffering from this syndrome are
abnormal males having two or more X-
chromosomes in addition to one Y-
chromosome (XXY, XXXY).
• They have a normal autosomal set of 22.
• The main features of this syndrome are that
the affected persons are eunuchoid males
with non-functional testis. Spermatozoa are
absent in their ejaculations.
• The growth of hair on face, axillae and
pubes is scanty.
• The condition is associated with
gynaecomastia and mental retardation.
• The incidence of this syndrome is about 1 in
1000 among males at birth

43. XYY SYNDROME
• The male with an extra Y-chromosome
has attracted much attention because
of his reported tendency to anti-social,
aggressive and often criminal
behaviour.
• The principal features of this syndrome
appear to be exceptional height
(usually six feet and over) and a serious
personality disorder leading to
behavioural disturbances
•
• The incidence of this syndrome is
about l in 1000 males at birth

44. TURNERS SYNDROME
• An incidence of 1 in 7,500 live born girls .
• Persons suffering from this syndrome are
apparent females with underdeveloped sex
glands.
• They have 45 chromosomes instead of the
normal complement of 46.
• Their sex chromosome constitution is XO
instead of XX . This abnormal condition is
due to non-disjunction of the sex
chromosomes.
• Clinically the patients are of short stature,
infertile and have primary amenorrhoea.
• They often show other congenital defects
such as coarctation of the aorta. pulmonary
stenosis, renal malformations and mental
retardation.

45. SUPER FEMALES
• Females with 3 to 5 X-chromosomes (XXX,
XXXX. XXXXX) have been found.
• In general, the higher the number of X-
chromosomes.
• The greater the degree of mental retardation
and congenital abnormalities, e.g.,
underdeveloped external genitalia, uterus and
vagina.

46. C H R O M O S O M A L D I S O R D E R S
R E L AT I N G T O A U T O S O M E S
• D o w n s y n d r o m e
• E d w a r d s y n d r o m e
• P a t a u s y n d r o m e

47. DOWN SYNDROME
• Mongolism or Down's Syndrome was described by
Langdon Down in 1866.
• Most cases of mongolism are caused by an extra
chromosome which occurs on the 21st pair. The anomaly
is therefore sometimes described as "Trisomy 21“
• The syndrome is easily recognized in the older child and
adult by the short stature and small round head, narrow,
tilted eye-slits, mat-formed ears, short broad hands, lax
limbs, mental retardation and quite a few other
abnormalities especially internal congenital defects such
as cardiac defects and atresia of the alimentary tract.
• The risk for a woman of 20 is estimated at about 1 in
3,000 and that for a woman of 45, 1 in 50

48. MENDELIAN DISEASES
1. Autosomal dominant traits
 Achondroplasias
 Huntington's disease
 Neurofibromatosis
 Marfans syndrome
 Retinoblastoma
 ABO blood group system
 Polycystic, kidney
2. Autosomal recessive traits
 Phenylketonuria
 Tay sachs disease
 Cystic fibrosis
 Megacolon
 Albinism
 Haemoglobinopathies
 Galactosemia
 Fibrocystic disease of the pancreas
3. Recessive sex-linked traits
 Hemophilia type A and B
 Color blindness
 G6PD Deficiency
 hydrocephalus
 Retinitis pigmentosa
 Agammaglobulinemia, Bruton type
 Duchenne type of muscular dystrophy
4. Dominant X-linked traits
 Vitamin D resistant rickets
 familial hypophosphatemia
 Blood group Xg

49. 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

50. AUTOSOMAL RECESSIVE
The disease appears in male and female children
of unaffected parents
e.g., Cystic Fibrosis, Phenylketonuria

51. 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

52. 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 Aand B, Color blindness

53. SICKLE CELL ANEMIA
• Autosomal recessive disorder in which an abnormal Hb leads to chronic
haemolytic anaemia with a variety of severe clinical consequences.
• Persons with 2 genes (homozygous) of this disease suffer from acute
anaemia and in most cases die before puberty.
• The rate of sickling is influenced by a number of factors, most importantly
by concentration of haemoglobin S in the individual red blood cell.
• The disease is prevalent among blacks, specially in certain parts of Africa .
It has been found that the areas where the disease is most prevalent also
showed the higher frequencies of malaria.
• The disorder has its onset during the first year of life, when haemoglobin
F level falls. These patients are prone to delayed puberty. On
examination, patients are often chronically ill and jaundiced. There is
hepatomegaly, but the spleen is not palpable in adult life. The heart is
enlarged, with hyperdynamic pericardium and systolic murmurs.
Nonhealing ulcers may be present.
• Sickle cell anaemia becomes a chronic multisystem disease, with death
from organ failure commonly occurring between ages 20 and 40 years.

54. THALASSEMIA
• Hereditary disorders characterized by reduction in the synthesis of globin chain (alpha or
beta).
• Reduced globin chain synthesis causes reduced haemoglobin synthesis and eventually
produces a hypochromic microcytic anaemia because of defective haemoglobinization of red
cells.
• Thalassaemia's can be considered among hypo-proliferative anaemias, the haemolytic
anaemias, and the anaemias related to abnormal haemoglobin, since all of these factors may
play a role.
• Alpha thalassaemia is primarily due to gene deletion directly causing reduced a - globin chain
synthesis.
• Beta thalassaemia are usually caused by point mutations rather than large deletions.
• Signs of thalassaemia develop after 6 months of age, because this is the time when
haemoglobin synthesis switches from haemoglobin F to haemoglobin A.
• Prenatal diagnosis is available for couples at risk of producing a child with one of the severe
thalassaemia syndromes. Asian couples whose parents on both sides have alpha thalassaemia

55. HEMOPHILIA
• Affecting 15-20 of every 100,000 males born, with equal incidence in all ethnic groups and
geographical areas that have been surveyed.
• Prevalence, which depends on survival, varies according to available medical care. There are an
estimated 420,000 people with haemophilia worldwide.
• There are different forms of haemophilia. While the disorder affects males, it is carried by
females, who are only occasionally affected, usually mildly.
• The disorder concerns the absence, decrease or deficient function of blood coagulating factor,
leading to excessive, prolonged or delayed bleeding.
• In severe cases it most commonly occurs in the large joints of the limbs. Unless such bleeding
is controlled promptly by infusion of the deficient factor, there is progressive joint disease and
muscle atrophy, leading to serious physical, psychological and social handicaps.
• Until recently, the foremost cause of death was haemorrhage, especially in the skull. In
countries with highly developed haemophilia care programmes, therapy with plasma
derivatives has reduced mortality.
• In the past decade, the main causes of death have stemmed from infections as the side-effects
of treatment, including AIDS and liver disease secondary to hepatitis.
• Survival in patients without these infections is almost the same as that of the general

56. CYSTIC FIBROSIS
• Cystic fibrosis is a genetic disease occurring worldwide, which affects the respiratory and
gastrointestinal tracts and the sweat glands.
• Incidence ranges from 2.5 to 5 per 10,000 live births in most European populations.
• Upto 95% of cases in Latin America are never diagnosed, and the life expectancy of those
that are diagnosed is only about 10 years.
• The gene defect in cystic fibrosis was identified in 1989, since then there has been
unprecedented progress in understanding the disease, leading to new approaches to
drug treatment and hopes for gene therapy.
• Such treatments are expected to be available within the lifetime of most current patients,
with a corresponding anticipated improvement in outlook.

57. PHENYLKETONURIA
• Phenylketonuria is an autosomal recessive disorder resulting in a deficiency of the liver
enzyme phenylalanine hydroxylase which converts phenylalanine to tyrosine.
• The name PKU is derived from the build-up of phenyl pyruvic acid in the urine, a
characteristic of the disease. The frequency of the disease is about 1 in 10,000 births
(5).
• Phenylalanine accumulates in the blood and tissues and has a toxic effect on the brain
leading to mental retardation.
• Tests for elevated blood levels of phenylalanine are much more desirable than tests for
urine phenyl ketone, since blood levels must be elevated before urine detection is
possible.
• Testing of bottle-fed infants should be done no sooner than 48 hours after the first
successful formula feeding.
• Breast-fed babies, however, are tested at 7 days, since breast milk often has little
protein content before the 5th day

58. MULTIFACTORIAL DISORDERS
• Influence of multiple genes and environmental factors
• These include mainly the non- communicable diseases
– Diabetes mellitus
– Hypertension
– Cardiovascular diseases
– Cancers

59. CANCER
• It is not yet certain whether most cancers are hereditary. But a genetic predisposition may
be involved in as many as 10-25% of cases of cancer of the breast or colon. Numerous
genes are being identified that may affect susceptibility to tumour development. This may
lead to a general improvement in the diagnosis and treatment of cancer. For example, a
DNA screening test for breast cancer could soon be available. Advice could be offered on
the chemoprevention of cancers, tailored for families with different types of cancer risk.
Mental disorders
• Evidence from family and twin studies demonstrate the existence of genetic predisposition
to some common mental diseases. Alzheimer's disease, the most common form of senile
dementia. has a strong familial tendency and is known to be caused by at least four different
genes. Research may lead to the development of drugs useful in preventing or delaying the
onset of the disease. Enough is already known about the genetics of common diseases to
introduce a family- oriented approach into basic as well as specialist medical practice. A
major effort is being made to study the genetic factors involved, develop appropriate
therapies, and determine how these approaches can best be applied in practice.

60. CORONARY HEART DISEASE
• Until recently, it was generally believed that environmental factors alone cause
coronary heart disease. But investigating family histories often uncover genetic risks.
Mapping the human genome will make the genetic predisposition to CHO much
easier. High blood pressure and high blood cholesterol levels, major risk factors in
CHO, are also genetically influenced. A combination of risk detection and lifestyle
counselling, with drug treatment, might cut the incidence of heart attacks to the low
levels as two or three generations ago
Diabetes
Evidence for a genetic element in insulin dependent diabetes mellitus has emerged
from studies showing a higher concordance in identical twins (25-30%) than in non-
identical twins (5-10%). About 85% of cases of diabetes in developed countries are of
the non-insulin dependent form of the disease, which has a particularly strong familial
tendency. Diabetes of all types is an important candidate for future treatments such as
gene therapy of pancreatic tissue transplantation.

61. ADVANCES IN MOLECULAR
GENETICS
• DNA Technology
• Gene Therapy
• The Human Genome Project
• The Human Genome Diversity Project
• Population genetics

62. ADVANCES IN MOLECULAR GENETICS
• DNA technology depends on a number of basic tools that have been gradually developed
over the past 20 years or so. A wide range of enzymes involved in DNA and RNA synthesis
and repair have been identified and become available for laboratory use, nucleotide bases
are available as laboratory reagents, and specific DNA sequences can be synthesized at will.
DNA diagnostic methods have been greatly simplified over the past 10 years. DNA has
many advantages for genetic diagnosis. It is easy to obtain, since every cell of an individual
or foetus contains the full DNA complement of that individual. Genes can be studied
whether they are actively producing their product or not. A definitive diagnosis can usually
be made in all genetic conditions.
• DNA technology
• Gene therapy
• The human genome project
• The human genome diversity project

63. DNA TECHNOLOGY
Major new techniques that are contributing to the advances in
medical genetics include the following :
• The synthesis of DNA probes with specific sequences that will
bind to and identify any complementary DNA sequences that may
be present. This allows genetic diagnosis and permits further
analysis of DNA by the examination of unknown sequences
adjacent to the known ones.
• DNA sequencing methods for the rapid analysis of unknown
DNA and the identification of mutations that give rise to disease.
• New diagnostic techniques, such as the use of restriction
enzymes that cut DNA consistently only at specific sequences,
and the polymerase chain reaction (PCR) for amplifying known
DNA sequences. Such methods allow simple and rapid diagnosis
using extremely small tissue samples. It is even becoming
possible to analyse the DNA contained in a single cell.

64. • Techniques for synthesis of DNA that allow the production of known sequences of increasing
length. Coding sequences produced in this way can be used for the production of therapeutic
agents such as insulin, erythropoietin and factor VIII. They may also be used in the creation of
transgenic animals and in gene therapy.
• Positional cloning strategies using genetic markers, which are now defined along the entire human
genome. These have greatly simplified the study of families. Even quite small kindreds can be
examined using highly informative probes, and disease mutations can be rapidly assigned to their
chromosomal position.
• In Vitro methods for examining the protein product of gene sequences with unknown functions.
• New cytogenetic techniques such as fluorescence in situ hybridization (FISH), which permits direct
visualization of the relationship of genes to one another in the nucleus of the living cell.
• Comparison between the DNA sequences of different genes and species. This helps elucidate the
mechanisms of evolution.
• Insertion of coding DNA sequences into animal embryos to create transgenic animals, including
animal models of human diseases. The availability of transgenic techniques and the use of
experimental site-specific mutagenesis are particularly valuable for studying the roles of specific
genes in multifactorial diseases, where combinations of different genotypes and environments can
be examined.
• Insertion of missing DNA sequences into individuals with genetically determined disorders, or the
excision of harmful sequences (gene therapy).

66. GENE THERAPY
 Gene therapy is the introduction of a gene sequence into a cell with the aim of
modifying the cell's behaviour in a clinically relevant fashion.
 It may be used in several ways, e.g., to correct a genetic mutation (as for cystic
fibrosis), to kill a cell (as for cancer} or to modify susceptibility (as for coronary artery
disease).
 The gene may be introduced using a virus (usually a retrovirus or adenovirus} or by
means of lipid or receptor targeting.
 There is now almost universal agreement that gene delivery to somatic cell to treat
disease is ethical, and that gene therapy should take its place alongside other forms
of medical treatment.

68. HUMAN GENOME PROJECT
• The human genome project was an international research effort to determine the
sequence of the human genome and identify the genes that it contains. The
project was coordinated by the national institutes of health and the US
department of energy. Additional contributors included universities across the
United States and international partners in the United Kingdom, France, Germany,
Japan, China and India. The human genome project formally began in 1990 and
was completed in 2003, 2 years ahead of its original schedule.
• The work of the human genome project has allowed researchers to begin to
understand the blueprint for building a person. As researcher learn about more
the functions of genes and proteins, this knowledge will have a major impact in
the fields of medicine, biotechnology and the life sciences.

69. GOALS OF HGP
Some of the important goals of HGP were as follows:
1. Identify all the approximately 20,000-25,000 genes in human DNA;
2. Determine the sequences of the 3 billion chemical base pairs that make up human
DNA;
3. Store this information in databases;
4. Improve tools for data analysis;
5. Transfer related technologies to other sectors, such as industries;
6. Address the ethical, legal, and social issues (ELSI) that may arise from the project.
7. The project also aimed to sequence the genomes of several other organisms that
are important to medical research, such as the mouse and the fruit fly.

70. SALIENT FEATURES OF HUMAN GENOME
 The human genome contains 3164.7 million bp.
The average gene consists of 3000 bases, but sizes vary greatly, with
the largest known human gene being dystrophin at 2.4 million bases.
The total number of genes is estimated at 30,000–much lower than
previous estimates of 80,000 to 1,40,000 genes. Almost all (99.9 per
cent) nucleotide bases are exactly the same in all people.
The functions are unknown for over 50 per cent of the discovered
genes.
Less than 2 per cent of the genome codes for proteins.
Repeated sequences make up very large portion of the human
genome.

71. Cont.
Repetitive sequences are stretches of DNA sequences that are repeated
many times, sometimes hundred to thousand times. They are thought to
have no direct coding functions, but they shed light on chromosome
structure, dynamics and evolution.
Chromosome 1 has most genes (2968), and the Y has the fewest (231).
Scientists have identified about 1.4 million locations where single base DNA
differences (SNPs – single nucleotide polymorphism, pronounced as ‘snips’)
occur in humans. This information promises to revolutionize the processes
of finding chromosomal locations for disease-associated sequences and
tracing human history

72. ETHICAL, LEGAL AND SOCIAL IMPLICATIONS
OF HUMAN GENOME PROJECT
• The ethical, legal and social implications (ELSI) program was founded in 1990 as an integral
part of the Human Genome Project. The mission of the ELSI program was to identify and
address issues raised by genomic research that would affect individuals, families, and
society. A percentage of the Human Genome Project budget at the National Institute of
Health and the US Department of Energy was devoted to ELSI research.
• The ELSI program focused on the possible consequences of genomic research in four main
areas:
a. Privacy and fairness in the use of genetic information, including the potential for
genetic discrimination in employment and insurance.
b. The integration of new genetic technologies, such as genetic testing, into the practice of
clinical medicine.
c. Ethical issues surrounding the design and conduct of genetic research with people,
including the process of informed consent.
d. The education of healthcare professionals, policy makers, students and the public
about genetics and the complex issues that result from genomic research.

73. THE HUMAN GENOME DIVERSITY
PROJECT
• As part of the work of HUGO, the Human Genome Diversity Project is aimed at increasing
understanding of human evolution.
• The major objective is to define the genetic relationships between human populations and interpret
them in terms of natural selection. genetic drift. migration, etc.
• Differences in distribution between populations may often be accounted for by "founder effects".
When a population expands from a relatively few founding members, some contribute more, and some
less, to the genetic make-up of subsequent generations.
• If one prolific founder carries a genetic abnormality, this can lead to a localized cluster of affected
individuals. Studies of isolated and aboriginal populations can be particularly informative

75. POPULATION GENETICS
• Population genetics has been defined as the study of the precise genetic composition of population and
various factors determining the incidence of inherited traits in them (10). Population genetics is founded on
a principle enunciated independently by Hardy in England and Weinberg in Germany in 1908.
• Let us consider the results when a human population consisting of tall (TT). intermediate (Tt) and short (tt)
individuals were allowed to mate at random. Even after several generations of interbreeding, it will be
found that there will be some individuals who are tall (TT) some intermediate (Tt) and some short (tt). In
other words, we cannot produce a race which is "pure" or uniform in height. The Hardy-Weinberg law
states that "the relative frequencies of each gene allele tends to remain constant from generation to
generation" in the absence of forces that change the gene frequencies. Thus, the study of gene frequencies,
and the influences which operate to alter the "gene pool" and their long-term consequences is the central
theme in population genetics.

77. FACTORS WHICH INFLUENCE THE
GENE FREQUENCIES
• The Hardy-Weinberg law assumes that human population is static. But in reality, human
population and consequently human gene pool is never static. There are several factors
which influence the human gene pool.
• The following are some :
– Mutation
– Natural selection
– Genetic drift
– migration

78. PREVENTIVE AND SOCIAL MEASURES
1. Health Promotion Measures
2. Specific Protection
3. Early Diagnosis And Treatment
4. Rehabilitation

79. 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.

80. EUGENICS
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 violenceS
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.

81. 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.

82. 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.
• 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

83. Genetic counselling may be prospective or retrospective
(i) Prospective genetic counselling : This allows for the true prevention of disease. This approach
requires identifying heterozygous individuals for any particular defect by screening procedures and
explaining to them the risk of their having affected children if they marry another heterozygote for
the same gene. In other words, if heterozygous marriage can be prevented or reduced, the prospects
of giving birth to affected children will diminish. The application in this field, for example, are sickle
cell anaemia and thalassemia. It is possible that this kind of prevention may find wider application to
cover a number of other recessive defects
(ii) Retrospective genetic counselling : Most genetic counselling is at present retrospective, i.e ., the
hereditary disorder has already occurred within the family. A survey carried out by the WHO
showed that genetic advice was chiefly sought in connection with congenital abnormalities, mental
retardation, psychiatric illness and inborn errors of metabolism and only a few sought premarital
advice. The WHO recommends the establishment of genetic counselling centres in sufficient
numbers in regions where infectious disease and nutritional disorders have been brought under
control and in areas where genetic disorders have always constituted a serious public health
problem (e.g., sickle cell anaemia and thalassaemia)

84. OTHER GENETIC PREVENTIVE
MEASURES
• Consanguineous marriages : When blood relatives marry each other there is an increased risk in the
offspring of traits controlled by recessive genes, and those determined by polygenes. Examples are
albinism, alkaptonuria, phenylketonuria and several others. An increased risk of premature death is also
noted in such offspring
• Late marriages : The pendulum is swinging in favour of early marriages. The discovery of "Trisomy 21" in
Mongols coupled with the knowledge that mongolism is more frequent in children born of elderly
mothers, lends support to the view that early marriage of females is better than late marriage from the
point of view of preventing mongolism. Its incidence in a mother at age 20 is only 1 : 3000; by the age
40, it is 1:40. 2

85. SPECIFIC PROTECTION
• Increasing attention now being paid to the protection of individuals and whole
community against mutagens such as X-rays and other ionizing radiations and also
chemical mutagens.
• Patients undergoing x- ray examination should be protected against unnecessary
exposure of the gonads to radiation.

86. EARLY DIAGNOSIS AND TREATMENT
• Detection of genetic carriers- it is now possible to identify the healthy carriers of a number of genetic disorders,
especially the inborn errors of metabolism. The female carriers of Duchenne type of muscular dystrophy, an X-
linked disorder, can now be detected by elevated levels of creatine kinase in 80% of carriers.
• Prenatal diagnosis- amniocentesis in early pregnancy about (14-16 weeks) has now made possible for prenatal
diagnosis of conditions associated with chromosomal anomalies (e.g., Down's Syndrome); many inborn e rrors of
metabolism (e.g., Tay-Sach's disease, galactosaemia, Maple syrup urine disease, Alpha-thalassaemia and neural
tube defects)
• Screening of new-born infants- we have today a long list of screening tests for early diagnosis of genetic
abnormalities- sex chromosome abnormalities, congenital dislocation of hip, etc. Neonates
should be routinely examined for congenital abnormalities, particularly dislocation of hip, which can be simply
corrected at this stage. Biochemical screening of new-born infants was first used for PKU in 1966.
• Recognizing pre-clinical cases- Genetic counselling can have the greatest impact when individuals or couples at
genetic risk are identified prospectively. i.e., before they have developed symptoms themselves or produced their
first affected child. Prospective counselling is technically possible only when carriers can be accurately identified.
Once diagnosed, some of the genetic conditions can be treated with complete or partial success by medical and
surgical measures. For example, diets low in phenylalanine are now prescribed as treatment for PKU children.
Modern surgical techniques have brought great improvements in dealing with cases of spina bifida.

87. INDICATIONS FOR PRENATAL
DIAGNOSIS
Indications Methods
Advanced maternal age, previous
child with chromosomal aberration,
intrauterine growth delay
Cytogenetics ( amniocentesis,
chorionic villus sampling)
Biochemical disorders Protein assay, DNA diagnosis,
sonography, fetoscopy, maternal
serum alpha- fetoprotein and
chorionic gonadotropin
Congenital anomaly ”
Screening for neural tube defects and
trisomy
”

88. AMNIOCENTESIS
• Examination of a sample of amniotic fluid makes possible the prenatal diagnosis of chromosomal anomalies and
certain metabolic defects. The procedure can be used as early as 14th week of pregnancy when abortion of the
affected fetus is still feasible. The diagnosis of chromosomal anomalies is made by culture and Karyotyping of fetal
cells from the amniotic fluid, and of metabolic defects by biochemical analysis of the fluid.
• Amniocentesis is called for in the following circumstances if the parents are prepared to consider abortion.
1. A mother aged 35 years or more (because of high risk of Down's syndrome with advanced maternal age).
2. Patients who have had a child with Down's syndrome or other chromosomal anomalies.
3. Parents who are known to have chromosomal translocation.
4. Parents who have had a child with a metabolic defect - detectable by amniocentesis. The most common
are defects of the neural tube, anencephaly and spina bifida which can be detected by an elevation of alpha
fetoprotein in the amniotic fluid.
5. When determination of the sex is warranted, given a family history of a sex-linked genetic disease e .g.,
certain muscular dystrophies. For the detection of neural tube defects there is now the possibility of
widespread screening by the determination of alpha-fetoprotein levels in the maternal serum. If the test is
positive it can be confirmed by amniocentesis

89. REHABILITATION
• Early referral of children with
genetic disorders which are
known to cause physical or
mental disability.

90. ESTABLISHED GENETIC POPULATION
SCREENING SERVICES
Type of service Conditions Preventive or screening action
Primary prevention Rhesus hemolytic disease
Congenital rubella
Congenital malformation
Postpartum use of anti- D globulin
Immunization of girls
Addition of folic acid to the maternal diet, control of maternal
diabetes, avoidance of mutagens such as alcohol, certain drugs
and possibly tobacco
Antenatal screening Congenital malformations
Chromosomal
abnormalities
Inherited diseases
USG fetal anomaly scan, maternal serum alpha-fetoprotein
estimation
Noting maternal age and maternal serum factors levels
Checking family history
Carrier screening for haemoglobinopathies, Tay Sachs disease
Neonatal screening Congenital malformations
Phenylketonuria,
congenital
hypothyroidism, sickle cell
disease
Examination of the newborn for early treatment
Biochemical tests for early treatment

91. PRACTICAL APPLICATION OF GENETICS IN NURSING
• All nurses have role in the delivery of genetic services & management of
genetic information. Nurses require genetic knowledge to identify,
support, refer & care for persons affected by or risk for genetic
disorders.
• Nurses can offer care that protects patients & families from the risk
associated with genetic information, including addressing family issues.
Nurses are also needed to refer patients to genetic specialist & assist in
making choice of genetic health care.
PRACTICAL APPLICATION OF GENETICS
IN NURSING

92. MAJOR PRACTICAL APPLICATIONS OF GENETIC IN
NURSING
Major Practical Applications of Genetic in Nursing
• Understands genetic basis of disease
• Early and effective diagnosis of genetic disorders.
• Contributes towards health promotion with genetic aspects
• Prevention of genetic conditions
• Management and care in genetic disorders
• Genetic information & counselling.
• Referral services
• Social & ethical issues in genetics

93. 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.

94. 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.

95. REFERENCES
1. K. Park. Textbook of Preventive and Social Medicine. Genetics and health: 2011:
23:820-830
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. Rawat HC, Brar NK. Textbook of advanced nursing practice: 2015: 1:205-263

97. THANK YOU