2. • Medical genetics is a relatively a new branch of
an old science. Familial occurrences of specific
traits have been cited in the literature.
• The era of molecular genetics was marked by the
discovery of a molecular defect in the sickle cell
disease, initially postulated by Linus Pauling in
1949.
• Genetics is the study of heredity. Heredity is a
biological process where a parent passes
certain genes onto their children or offspring.
Every child inherits genes from both of their
biological parents and these genes in turn
express specific traits.
3. TERMINOLOGIES
GENE: a gene is a segment of nucleic acid that
contains genetic information necessary to control a
certain function, such as the synthesis of a
polypeptide. The genetic information lies within the
cell nucleus of each living cell in the body
CHROMOSOME: a chromosome is a filament-
like nuclear structure consisting of chromatin that
stores genetic information as base sequences in
DNA and whose number is constant in each species.
The genes lie within the chromosomes.
KARYOTYPE: a karyotype is the chromosomal
constitution of an individual, which is represented
by a laboratory- made display, in which
chromosomes are arranged by size and centromere
position.
4. GENETICS: it is a discipline
of biology, is the science
of genes, heredity, and a
variation in living organisms.
ALLELES: - All the different
molecular forms of the same
genes. - It is an alternative form
of a gene that can be present on
either one or both of a pair of
homologous chromosomes.
5. MUTATION: permanent change in
nucleotide sequence or arrangement of
DNA
POLYMORPHISM: ≥ 2 relatively common
(each > 1% in population) alleles at a locus in
the population.
LOCUS - Each gene has a specific location locus on
a chromosome. A pair of homologous chromosomes,
each in the unduplicated state (most often, one from
a male parent and its partner from a female parent)
A gene locus (plural, loci), the location for a specific
gene on a specific type of chromosome
6. GENOTYPE: Particular genes and individual
carries / the genes that an organism inherits from
each parent. E.g. Genotype: TT @ Tt @ tt
PHENOTYPE: An individual’s observable traits/
the protein used by these genes that determine the
organism’s physical characteristic. E.g.: Phenotype:
Tall or dwarf Two terms help keep the distinction
clear between genes and the traits they specify
HOMOZYGOUS: Having the same alleles at a
particular gene locus on homologous chromosomes.
Or when both alleles of a pair are identical. So,
homozygous dominant has a pair of dominant
alleles (AA), homozygous recessive has a pair of
recessive alleles (aa).
7. HETEROZYGOUS: Having different alleles at one or more
corresponding chromosomal loci. When the two alleles of a
pair are not identical, so, heterozygous has a pair of non-
identical allele (Aa). We used capital letters for dominant
alleles and lowercase letters for the recessive one. Example, A
and a.
AUTOSOMES
Chromosomes 1-22
An individual inherits one chromosome from each parent
An individual therefore inherits a paternal copy and a
maternal copy of an autosomal
SEX CHROMOSOMES
X and Y
A female inherits an X from their mother and an X from their
father
A male inherits an X from their mother and the Y from their
father
8. SINGLE GENE INHERITANCE
Single-gene traits are often called ‘Mendelian’
because like the garden peas studied by Gregor
Mendel, they occur in fixed proportions among
the offspring of specific types of mating.
Single-gene disorders are primarily disorders of
the pediatric age range greater than 90%
manifest before puberty only 1% occur after the
end of the reproductive period.
9. PATTERNS OF SINGLE GENE
INHERITANCE
• Whether the gene is
on an autosome or a
sex chromosome
1.
• Whether the
phenotype is
dominant or recessive
2.
10. 4 BASIC PATTERNS OF SINGLE
GENE INHERITANCE
X-linked
Dominant
X-linked
Recessive
Autosomal
Dominant
Autosomal
Recessive
11. AUTOSOMAL RECESSIVE
Autosomal recessive is one of several ways that a trait, disorder, or
disease can be passed down through families.
• An autosomal recessive disorder means two copies of an abnormal
gene must be present in order for the disease or trait to develop.
• Information
• Inheriting a specific disease, condition, or trait depends on the type
of chromosome that is affected.
• The two types are autosomal chromosomes and sex chromosomes.
• It also depends on whether the trait is dominant or recessive.
• A mutation in a gene on one of the first 22 nonsex chromosomes can
lead to an autosomal disorder.
• Genes come in pairs. One gene in each pair comes from the mother,
and the other gene comes from the father. Recessive inheritance
means both genes in a pair must be abnormal to cause disease.
People with only one defective gene in the pair are called carriers.
These people are most often not affected with the condition.
However, they can pass the abnormal gene to their children.
12. CHANCES OF INHERITING A TRAIT
• If you are born to parents who carry the same autosomal recessive
change (mutation), you have a 1 in 4 chance of inheriting the
abnormal gene from both parents and developing the disease. You
have a 50% (1 in 2) chance of inheriting one abnormal gene.
This would make you a carrier.
• In other words, for a child born to a couple who both carry the gene
(but do not have signs of disease), the expected outcome for each
pregnancy is:
• A 25% chance that the child is born with two normal genes (normal)
• A 50% chance that the child is born with one normal and one
abnormal gene (carrier, without disease)
• A 25% chance that the child is born with two abnormal genes (at
risk for the disease)
• Note: These outcomes do not mean that the children will definitely
be carriers or be severely affected.
13. AUTOSOMAL DOMINANT
Autosomal dominant is one of several ways that a
trait or disorder can be passed down (inherited)
through families.
• In an autosomal dominant disease, if you inherit
the abnormal gene from only one parent, you
can get the disease. Often, one of the parents
may also have the disease.
14. Dominant inheritance means an abnormal gene from
one parent can cause disease. This happens even when
the matching gene from the other parent is normal. The
abnormal gene dominates.
This disease can also occur as a new condition in a child
when neither parent has the abnormal gene.
A parent with an autosomal dominant condition has a
50% chance of having a child with the condition.
This is true for each pregnancy.
It means that each child's risk for the disease does not
depend on whether their sibling has the disease.
Children who do not inherit the abnormal gene will not
develop or pass on the disease.
If someone is diagnosed with an autosomal dominant
disease, their parents should also be tested for the
abnormal gene.
16. AUTOSOMAL DOMINANT
INHERITANCE, AD
• The gene concerned to single-gene disorder was
located on an autosome, and the phenotype is
dominant. It can be:
1. Completely dominant
2. Incompletely dominant
3. Irregularly dominant
4. Co dominant
5. Delayed dominant
6. Sex-influenced dominance
17. CHARACTERISTICS OF
AUTOSOMAL DOMINANT
INHERITANCE
• The phenotype usually appears in every generation,
each affected person having an affected parent.
• Any child of an affected parent has a 50 percent risk
of inheriting the trait.
• Phenotypically normal family members do not
transmit the phenotype to their children.
• Males and females are equally likely to transmit the
phenotype, to children of either sex.
• A significant proportion of isolated cases are due to
new mutation
18. • COMPLETELY DOMINANT: A phenotype
expressed in the same way in both homozygotes and
heterozygotes are completely dominant. Eg.
Brachydactyly and Syndactyly type.
19. INCOMPLETELY DOMINANT: The
phenotype due to a heterozygous
genotype is different from the
phenotype seen in both
homozygous genotypes and
its severity is intermediate
between them.
• E.g., Achondroplasia:
Improper development of
cartilage at the ends of the
long bones, resulting in a
form of congenital dwarfism.
20. • IRREGULAR DOMINANT: The phenotypes of some of the
heterozygotes, for some reason, do not appear as affected. It
can be seen as a skipped generation.
• Marfan Syndrome: it is a disorder of connective tissue
involving a triad of ocular, skeletal and cardiovascular
alterations. The most common ocular abnormality is a
subluxation of the lens. Common skeletal findings include tall
stature, arachnodactylic (spider-like) hands and feet and
scoliosis. Severe scoliosis may compromise respiratory
function in pregnant women with Marfan Syndrome. The
major life threatening risk, however is the frequent occurrence
of aortic fusiform or dissecting aneurysms. Fifty percent of
aortic aneurysms in affected women under age 40occur
during pregnancy with rupture most likely to occur during
pregnancy.
21.
22. • CODOMINANT: Of or relating to two alleles of a gene
pair in a heterozygote that are both fully expressed.
Blood type-- type AB is codominant because both the
antigen A and antigen B show up in the genotype.
23.
24. • DELAYED DOMINANT: The individual who carries
mutant allele doesn’t onset until particular age.
• E.g., Huntington’s disease: it is an inherited disease that
causes certain nerve cells in the brain to waste away.
People are born with the defective gene, but symptoms
usually don't appear until middle age. Early symptoms of
HD may include uncontrolled movements, clumsiness or
balance problems. Later, HD can take away the ability to
walk, talk or swallow. Some people stop recognizing
family members. Others are aware of their environment
and are able to express emotions. HD is the most common
genetic cause of abnormal involuntary writhing
movements called chorea, which is why the disease used
to be called Huntington's chorea.
25.
26. • Sex-influenced dominance: The tendency for gene
action to vary between the sexes within a species.
• For example, the presence of horns in some breeds of
sheep appears to be dominant in males but recessive in
females and baldness in human.
28. AUTOSOMAL RECESSIVE
INHERITANCE
• Autosomal recessive inheritance, AR: The gene
concerned to single-gene disorder is located on an
autosome, and the phenotype is recessive.
• Consanguinity: Relationship by blood or by a
common ancestor. The chance that both parents are
carriers of a mutant allele at the same locus is
increased substantially if the parents are related and
could each have inherited the mutant allele from a
single common ancestor, a situation called
consanguinity.
29. CHARACTERISTICS OF
AUTOSOMAL RECESSIVE
INHERITANCE
• An AR phenotype, if it appears in more than one member
of a kindred, typically is seen only in the sibship of the
proband, not in parents, offspring, or other relatives.
• For most AR diseases, males and females are equally
likely to be affected.
• Parents of an affected child are asymptomatic carriers of
mutant alleles.
• The parents of the affected person may in some cases be
consanguineous.
• This is especially likely if the gene responsible for the
condition is rare in the population.
• The recurrence risk for each sib of the proband is 1 in 4.
30. CYSTIC FIBROSIS: CF is a disorder of the cells that
line the lungs, small intestines, sweat glands and
pancreas. Sticky, thick mucus contributes to the
destruction of lung tissue and impedes gas exchange in
the lungs. It also prevents nutrient absorption in the
small intestine, and blocks pancreatic ducts from
releasing digestive enzymes.
Cystic fibrosis (CF) is caused by a defect in a gene
called the cystic fibrosis transmembrane conductance
regulator (CFTR) gene. This gene makes a protein that
controls the movement of salt and water in and out of
the cells in your body. In people with CF, the gene does
not work effectively.
31.
32. • MUCOPOLYSACCHARIDOSES: this diverse group
of mucopolysaccharidoses accumulation disorders
(MPS) encompasses 6 different sydromes whose
primary types are: Hurler syndrome (type I), Hunter
syndrome (type II), Sanfilippo’s syndrome (type III)
and Mosquito syndrome (type IV). Individuals with
these diseases exhibit coarse faces in infancy, short
stature, skeletal and joint deformities, deafness, cornel
clouding, umbilical hernia, progressive mental
retardation.
33.
34. PHENYLKETONURIA: is an autosomal
recessive metabolic genetic disorder characterized by a
mutation in the gene for the hepatic
enzyme phenylalanine hydroxylase (PAH), rendering it
non-functional. This enzyme is necessary to metabolize
the amino acid phenylalanine (Phe) to the amino
acid tyrosine. When PAH activity is reduced,
phenylalanine accumulates and is converted
into phenylpyruvate (also known as phenylketone),
which is detected in the urine. Phenylalanine plays a
role in the body's production of melanin, the pigment
responsible for skin and hair color. Therefore, infants
with the condition often have lighter skin, hair, and
eyes than brothers or sisters without the disease.
35.
36. • SICKLE CELL DISEASE: or sickle-cell
anaemia (SCA) is an
autosomal recessive genetic blood disorder with over
dominance, characterized by red blood cells that
assume an abnormal, rigid, sickle shape. Sickling
decreases the cells' flexibility and results in a risk of
various complications. The sickling occurs because of
a mutation in the haemoglobin gene. Life expectancy is
shortened.
37.
38. • TAY- SACHS DISEASE: Tay–Sachs disease (also known as GM2
gangliosidosis or hexosaminidase A deficiency) is a rare autosomal
recessive genetic disorder. In its most common variant (known as infantile
Tay–Sachs disease), it causes a progressive deterioration of nerve cells and
of mental and physical abilities that commences around six months of age
and usually results in death by the age of four.
• The disease occurs when harmful quantities of cell membrane components
known as gangliosides accumulate in the brain’s nerve cells, eventually
leading to the premature death of the cells. A ganglioside is a form of
sphingolipid, which makes Tay–Sachs disease a member of
the sphingolipidoses.
• There is no known cure or treatment. Infants with Tay-Sachs disease
appear to develop normally for the first few months of life. Then, as nerve
cells become distended with fatty material, mental and physical abilities
deteriorate. The child becomes blind, deaf, and unable to swallow. Muscles
begin to atrophy and paralysis sets in
42. CHARACTERISTICS OF X-LINKED
RECESSIVE INHERITANCE
• The incidence of the trait is much higher in males than in
females.
• The gene responsible for the condition is transmitted
from an affected man through all his daughters. Any of
his daughters’ sons has a 50% chance of inheriting it.
• The gene is ordinarily never transmitted directly from
father to son, but it is transmitted by an affected male to
all his daughters.
• The gene may be transmitted through a series of carrier
females; if so, the affected males in a kindred are related
through females.
• Heterozygous females are usually unaffected, but some
may express the condition with variable severity as
determined by the pattern of X inactivation.
43. • DUCHENNE’S MUSCULAR DYSTROPHY: it is a
recessive X-linked form of muscular dystrophy, affecting
around 1 in 3,600 boys, which results in muscle
degeneration and eventual death.The disorder is caused
by a mutation in the dystrophin gene, located on the
human X chromosome, which codes for
the protein dystrophin, an important structural component
within muscle tissue that provides structural stability to
the dystroglycan complex (DGC) of the cell membrane.
While both sexes can carry the mutation, females rarely
exhibit signs of the disease.
• Symptoms usually appear before age 6 and may appear as
early as infancy. They may include:
• Fatigue
• Learning difficulties (the IQ can be below 75)
• Intellectual disability (possible, but does not get
worse over time)
44. • Muscle weakness
▫ Begins in the legs and pelvis, but also occurs less severely
in the arms, neck, and other areas of the body
▫ Difficulty with motor skills (running, hopping, jumping)
▫ Frequent falls
▫ Trouble getting up from a lying position or climbing stairs
▫ Weakness quickly gets worse
• Progressive difficulty walking
▫ Ability to walk may be lost by age 12, and the child will
have to use a wheelchair
▫ Breathing difficulties and heart disease usually start by age
20.
45.
46. • GLUCOSE -6- PHOSPHATE DEHYDROGENASE
DEFICIENCY: it is usually asymptomatic until the
affected male is exposed to one of many environmental
triggers, such as certain drugs (antimalarial agents,
aspirin, and sulphonamides) or certain foods (especially
fava beans). Pregnancy in women with G6PD defiency
(homozygotes) presents several complications.
Haemolytic episodes are more frequent, urinary
infections common in pregnancy, cannot be treated with
sulpha based drugs and exposure of a fetus with G6PD
deficiency may result in fetal hemolysis, hydrops fetalis
and death. The incidence of anemia, hyperbilirubinemia
and kernicterus is also increased among newborns with
G6PD deficiency.
47. • HEMOPHILIA A: Hemophilia A is an X-linked,
recessive disorder caused by deficiency of functional
plasma clotting factor VIII (FVIII), which may be
inherited or arise from spontaneous mutation. The
development of inhibitory antibodies to FVIII can
result in acquired hemophilia A or can complicate the
treatment of genetic cases. Depending on the level of
FVIII activity, patients with hemophilia may present
with easy bruising, inadequate clotting of traumatic
injury or—in the case of severe hemophilia—
spontaneous haemorrhage.
48. Signs of haemorrhage include the following:
• General: Weakness, orthostasis, tachycardia, tachypnea
• Musculoskeletal (joints): Tingling, cracking, warmth,
pain, stiffness, and refusal to use joint (children)
• CNS: Headache, stiff neck, vomiting, lethargy, irritability,
and spinal cord syndromes
• Gastrointestinal: Hematemesis, melena, frank red blood
per rectum, and abdominal pain
• Genitourinary: Haematuria, renal colic, and post
circumcision bleeding
• Other: Epistaxis, oral mucosal haemorrhage, hemoptysis,
dyspnea (hematoma leading to airway obstruction),
compartment syndrome symptoms, and contusions;
excessive bleeding with routine dental procedures.
52. CHARACTERISTICS OF X-LINKED
DOMINANT INHERITANCE
• Affected males with normal mates have no affected
sons and no normal daughters.
• Both male and female offspring of female carriers
have a 50% risk of inheriting the phenotype.
• For rare phenotypes, affected females are about twice
as common as affected males, but affected females
typically have milder (though variable) expression of
the phenotype.
53. • HYPOPHOSPHATEMIC RICKETS (vitamin
D-resistant rickets): The ability of the kidney
tubules to reabsorb filtered phosphate is
impaired. Although both sexes are affected, the
serum phosphate level is less depressed and the
rickets less severe in heterozygous females than
in affected males.
54.
55. SEX CHROMOSOMES
ABNORMALITIES
GENOTYPE GENDER SYNDROME PHYSICAL
TRAITS
XXY, XXYY,
XXXY
Male Klinefelter
Syndrome
Sterility, small
testicles, breast
enlargement
XO Female Turner’s
Syndrome
Sex organs don’t
mature at
adolescence,
sterility, short
stature
XXX Female Trisomy X Tall stature,
learning
disabilities,
limited fertility
56. GENETIC TESTING
• DEFINITION
Genetic testing is defined as examining a sample
of blood or other body fluids or tissue for bio-
chemical, chromosomal, or genetic markers that
indicate the presence or absence of genetic
diseases.
• It is also defined as a type of medical test that
identifies changes in chromosomes, genes or
proteins.
57. PURPOSES OF GENETIC TESTING
1.
• Carrier screening, which involves identifying unaffected
individuals who carry one copy for the disease to be expressed.
2.
• Pre- implantation genetic diagnosis
3.
• Pre- natal diagnostic testing
4. • New born screening
58. 5.
• Pre- symptomatic testing for estimating the risk of
adult onset cancers and Alzheimer’s disease.
6.
• Confirmational diagnosis of a symptomatic
individual.
7.
• Forensic and identity testing.
8.
• Pre- symptomatic testing for predicting adult onset disorders such as
Huntington’s disease.
• It allows the genetic diagnosis of vulnerabilities to inherited diseases.
9.
• It can be used to determine a child’s paternity or a
person’s ancestory.
59. TYPES OF GENETIC TESTING
NEWBORN SCREENING
This test is used just after birth to identify
genetic disorders that can be treated early
in life. The routine testing of infants for
certain disorders is the most wide spread
use of genetic testing. Newborn screening
is done to test for phenylketonuria and
congenital hypothyroidism.
DIAGNOSTIC TESTING
It is used to diagnose or rule out a specific
genetic or chromosomal condition. In many
cases, genetic testing is used to confirm a
diagnosis when a particular condition is
suspected based on physical mutations and
symptoms. The result of a diagnostic test can
influence a person’s choices about health care
and the management of the diseases.
60. CARRIER TESTING
It is used to identify people who carry
one copy of a gene mutation that when
present in two copies, causes a genetic
disorder. This type of testing is offered to
individuals who have a family history of
genetic disorder and to people in ethnic
groups with a n increased risk of specific
genetic conditions.
PRENATAL TESTING
It is used to detect changes in the fetal genes or
chromosomes before birth. This type of testing is
offered to couples with a n increased risk of
having a baby with genetic or chromosomal
disorder.
61. PREIMPLANTAION GENETIC
DIAGNOSIS
Genetic testing procedures that are
performed on human embryos prior
the implantation as part of an in vitro
fertilization procedure.
PREDICTIVE AND
PRESYMPTOMATIC TESTING
These tests are used to detect gene
mutations associated with disorders that
appear after birth, often later in life.
Presymptomatic testing can determine
whether a person will develop a genetic
disorder, before any signs or symptoms
appear.
62. FORENSIC TESTING
It uses DNA sequences to identify an
individual for legal purposes. Unlike
the test described above, forensic
testing is not used to detect gene
mutations associated with diseases.
This type of testing can identify crime
or catastrophic victims, rule out or
implicate a crime suspect or establish
biological relationships between
people.
PARENTAL TESTING
This type of genetic tests uses special DNA
markers to identify the same or similar
inherirance patterns between related
individuals.
63. RESEARCH TESTING
These tests uses special DNA markers
to identify unknown genes, learning
how genes work and advancing our
understanding of genetic conditions.
The result of testing done as part of a
research study are usually not
available to patients or their health
care providers.
PHARMACOGENOMICS
It is type of genetic testing that determines the
influence of genetic variations on drug
response.
64. ETHICAL, LEGAL, AND SOCIAL
ISSUES IN GENETIC TESTING
• Information from genetic testing can affect the lives of
individuals and their families. In addition to personal and
family issues, genetic disease or susceptibility may have
implications for employment and insurance. Therefore,
careful consideration in the handling of this information is
very important. Critical issues include:
• Privacy - the rights of individuals to maintain privacy. Some
genetic tests are required or strongly encouraged for
developing fetuses and newborn babies. If an infant is found to
be a carrier or likely to develop or be affected by an inherited
disease, these findings may affect the future employability or
insurability of the individual.
65. • Informed consent - obtaining permission to do
genetic testing. One must have knowledge of the
risks, benefits, effectiveness, and alternatives to
testing in order to understand the implications of
genetic testing.
• Confidentiality - acknowledgment that genetic
information is sensitive and access should to limited
to those authorized to receive it. Future access to a
person's genetic information also should be limited.
66. MEDICAL PROCEURE
• Genetic testing is often done as part of a genetic consultation and as of
mid-2008 there were more than 1,200 clinically applicable genetic tests
available .Once a person decides to proceed with genetic testing, a medical
geneticist, genetic counselor, primary care doctor, or specialist can order
the test after obtaining informed consent.
• Genetic tests are performed on a sample of blood, hair, skin, amniotic
fluid (the fluid that surrounds a fetus during pregnancy), or other tissue.
For example, a medical procedure called a buccal smear uses a small brush
or cotton swab to collect a sample of cells from the inside surface of the
cheek. Alternatively, a small amount of saline mouthwash may be swished
in the mouth to collect the cells.
• The sample is sent to a laboratory where technicians look for specific
changes in chromosomes, DNA, or proteins, depending on the suspected
disorder. The laboratory reports the test results in writing to a person's
doctor or genetic counselor.
• Routine newborn screening tests are done on a small blood sample
obtained by pricking the baby's heel with a lancet.
68. Planning for
possible
complications
with the birth
process
Planning for
problems that
may occur in
the newborn
infant
Deciding
whether to
continue the
pregnancy
Finding
conditions
that may
affect future
pregnancies.
71. HUMAN GENOME PROJECT
• Begun formally in 1990, the US Human Genome
Project was a 13 year old effort coordinated by the
U.S. Department of Energy and the National
Institutes of Health. The project originally was
planned to last 15 years, but rapid technological
advances accelerated the completion date to 2003.
72. PROJECT GOALS WERE TO
Identify all the approximately 20,000-25,000
genes in human DNA
determine the sequences of the 3 billion
chemical base pairs that make up human DNA,
store this information in databases,
73. improve tools for data analysis
transfer related technologies to the
private sector,
address the ethical, legal, and social issues
(ELSI) that may arise from the project
74. WHAT'S A GENOME? WHY IS IT
IMPORTANT?
• A genome is all the DNA in an organism,
including its genes. Genes carry information for
making all the proteins required by all
organisms. These proteins determine, among
other things, how the organism looks, how well
its body metabolizes food or fights infection, and
sometimes even how it behaves.
• DNA is made up of four similar chemicals (called
bases and abbreviated A, T, C, and G) that are
repeated millions or billions of times throughout
a genome. The human genome, for example, has
3 billion pairs of bases.
75. • The particular order of As, Ts, Cs, and Gs is
extremely important. The order underlies all of
life's diversity, even dictating whether an
organism is human or another species such as
yeast, rice, or fruit fly, all of which have their
own genomes and are themselves the focus of
genome projects. Because all organisms are
related through similarities in DNA sequences,
insights gained from nonhuman genomes often
lead to new knowledge about human biology.
76. KEY FINDINGS OF GENOME
PROJECT
• There are approximately 30,000genes in human beings,
the same range as in mice and twice that of roundworms.
• All human races are 99.99% alike, so racial differences
are genetically insignificant. This could mean all humans
are descended from a single original mother.
• Most genetic mutation occurs in the male of the species
and as agents of change. They are also more likely to be
responsible for genetic disorders.
• Genomics has led to advances in genetic archaeology and
has improved our understanding of how we evolved as
humans and diverged from apes 25 million years ago. It
also tells how our body works, including the mystery
behind how the senses of taste works.
77. TWO FACTORS THAT MADE THIS
PROJECT A SUCCESS ARE
1.
2.
• Genetic engineering
Techniques, with
which it is possible
to isolate and clone
any segment of
DNA.
• Availabilty of simple
and fast
technologies, for
determining the
DNA sequence.
78. ADVANTAGES OF HUMAN GENOME
PROJECT
Knowledge of the effects of
variation of DNA among
individuals can revolutionize
the ways to diagnose, treat
and even prevent a number
of diseases that affects the
human beings
It provides clues to
the understanding of
human biology.
79. ANTICIPATED BENEFITS OF
GENOME RESEARCH
Improve diagnosis of disease.
Detect genetic predispositions to disease.
Create drugs based on molecular information.
Use gene therapy and control systems as drugs
design “custom drugs” (pharmacogenomics)
based on individual genetic profiles
MOLECULAR MEDICINE
80. Rapidly detect and treat pathogens (disease-
causing microbes) in clinical practice.
Develop new energy sources (biofuels).
Monitor environments to detect pollutants.
Protect citizenry from biological and chemical
warfare.
Clean up toxic waste safely and efficiently.
MICROBIAL GENOMICS
81. Evaluate the health risks faced by individuals who
may be exposed to radiation (including low levels
in industrial areas) and to cancer-causing
chemicals and toxins
RISK ASSESSMENT
82. Study evolution through germline mutations in
lineages.
Study migration of different population groups
based on maternal inheritance.
Study mutations on the y chromosome to trace
lineage and migration of males.
BIOARCHAEOLOGY, ANTHROPOLOGY, EVOLUTION, AND
HUMAN MIGRATION
83. Identify potential suspects whose DNA may
match evidence left at crime scenes.
Exonerate persons wrongly accused of crimes.
Identify crime and catastrophe victims
establish paternity and other family
relationships.
DNA IDENTIFICATION(FORENSICS)
84. Grow disease-, insect-, and drought-resistant
crops.
Breed healthier, more productive, disease-
resistant farm animals.Grow more nutritious
produce.
Develop biopesticides.
Incorporate edible vaccines incorporated into
food products.
AGRICULTURE, LIVESTOCK BREEDING, AND
BIOPROCESSING
85. ETHICAL, LEGAL, AND SOCIAL
ISSUES
• Privacy and confidentiality of genetic information.
• Fairness in the use of genetic information by insurers, employers, courts,
schools, adoption agencies, and the military, among others.
• Psychological impact, stigmatization, and discrimination due to an individual’s
genetic differences.
• Reproductive issues including adequate and informed consent and use of
genetic information in reproductive decision making.
• Clinical issues including the education of doctors and other health-service
providers, people identified with genetic conditions, and the general public
about capabilities, limitations, and social risks; and implementation of
standards and quality-control measures.
• Uncertainties associated with gene tests for susceptibilities and complex
conditions (e.g., heart disease, diabetes, and Alzheimer’s disease).
• Health and environmental issues concerning genetically modified (GM) foods
and microbes.
• Commercialization of products including property rights (patents, copyrights,
and trade secrets) and accessibility of data and materials.
86. GENETIC COUNSELLING
• DEFINITION
• Genetic counseling is the process by which patients or
relatives, at risk of an inherited disorder, are advised of
the consequences and nature of the disorder, the
probability of developing or transmitting it, and the
options open to them in management and family
planning. This complex process can be separated into
diagnostic (the actual estimation of risk) and supportive
aspects.
• Genetic Counseling…is a communication process
which deals with problems associated with the
occurrence or the risk of recurrence of a birth defect or
a genetic disease in a family.
87. This process integrates:
• Interpretation of family and medical
histories to assess the chance of
disease occurrence or recurrence.
• Education about inheritance, testing,
management, prevention, resources
• Counseling to promote informed
choices and adaptation to the risk or
condition.
88. GENETIC COUNSELLING IS THE
PROCESS OF
Evaluating the
results of this
investigation
Evaluating
family history
and medical
records
Helping parents
understand and
reach decisions
about what to do
next.
Ordering
genetic tests
89. COUNSEELING SESSION
STRUCTURE
• The goals of genetic counselling are to increase
understanding of genetic diseases, discuss disease
management options, and explain the risks and
benefits of testing.
• Counselling sessions focus on giving vital, unbiased
information and non-directive assistance in the
patient's decision making process.
90. • Seymour Kessler, in 1979, first categorized sessions
in five phases:
Intake phase,
An initial contact phase
The encounter phase
Summary phase
Follow up phase
91. • The intake and follow-up phases occur outside of the
actual counselling session.
• The initial contact phase is when the counsellor and
families meet and build rapport.
• The encounter phase/communication phase includes
dialogue between the counsellor and the client about the
nature of screening and diagnostic tests.
• The summary phase provides all the options and
decisions available for the next step. If counselees wish to
go ahead with testing, an appointment is organized and
the genetic counsellor acts as the person to communicate
the results.
92. INDICATIONS FOR GENETIC
COUNSELLING
If a standard prenatal screening test (such as α
fetoprotein test) yields an abnormal result
An amniocentesis yields n unexpected results
(such as chromosomal defect in the unborn
baby).
Either parent or close relative has an in
heritance disease or birth defect, either parents
already has children with birth defect or
genetic disorders
93. The mother has had two or more miscarriage
or a baby dies in infancy. The mother is 35yrs
of age or over.
The partner is blood relatives.
94. GENETIC COUNSELLORS
• A genetic counsellor is an expert with a Master of
Science degree in genetic counselling.
• In the United States they are certified by the American
Board of Genetic Counselling. In Canada, genetic
counsellors are certified by the Canadian Association of
Genetic Counsellors.
• Most enter the field from a variety of disciplines,
including biology, genetics, nursing, psychology, public
health and social work.
• Genetic counsellors should be expert educators, skilled in
translating the complex language of genomic medicine
into terms that are easy to understand.
95. • Genetic counsellors work as members of a health care team and act as
a patient advocate as well as a genetic resource to physicians.
• Genetic counsellors provide information and support to families who have
members with birth defects or genetic disorders, and to families who may be
at risk for a variety of inherited conditions.
• They identify families at risk, investigate the problems present in the family,
interpret information about the disorder, analyse inheritance patterns and
risks of recurrence, and review available genetic testing options with the
family.
• Genetic counsellors are present at high risk or specialty prenatal clinics that
offer prenatal diagnosis, paediatric care centres, and adult genetic centres.
• Genetic counselling can occur before conception (i.e. when one or two of
the parents are carriers of a certain trait) through to adulthood (for adult
onset genetic conditions, such as Huntington's disease or
hereditary cancer syndromes).
96. PURPOSE
• Provide concrete, accurate information about
inherited disorders.
• Reassure people who are concerned that their child
may inherit a particular disorder that the disorder will
not occur.
• Allow people who are affected by inherited disease to
make informed choice about future reproduction.
• Educate people about inherited disorder and the
process of inheritance.
• Offer support by skilled health care professionals to
people who are affected by genetic disorders.
97. STEPS OF GENETIC COUNSELING
History: A proper record of the history of the patient is necessary: This
includes both present and relevant past history. Family history includes
siblings and other relatives also. Obstetric history of includes exposure to
teratogens (drugs, X-rays) in pregnancy. History of abortion or still birth if
any, should be recorded Enquiry should be made about consanguinity as it
increases the risk especially in autosomal recessive disorders.
Pedigree Charting: At a glance this offers in a concise manner the state of
disorder in a family. It forms an indispensable step towards counselling.
Estimation of Risk: It forms one of the most important aspects of genetic
counselling. It is often called recurrence risk. To estimate it one requires to
take into account following points:
• Mode of inheritance
• Analysis of pedigree or family tree
• Results of various tests
98. Transmitting Information: After completing the diagnosis, pedigree charging
and estimation of risk the next most important step is of communicating this
information to the consultants. This important functioning involves various factors
such as:
• Psychology of the patient.
• The Emotional stress under prevailing circumstances.
• Attitude of family members towards the patients.
• Educational, social and financial background of the family.
• Gaining confidence of consultants in subsequence meetings during follow up.
• Ethical, moral and legal implications involved in the process.
• Above all, communication skills to transmit facts in an effective manner i.e. making
them more acceptable and palatable.
Management: In genetics, “Treatment” implies a very limited scope. It naturally
aims for prevention rather than cure. In fact for most of the genetic disorders cure
is unknown. Treatment is therefore directed towards minimizing the damage by
early detection and preventing further irreversible damage. For example in PKU,
i.e. phenylketonuria. This disorder is characterized by a deficiency of
phenylalanine hydroxylase enzyme, which is necessary for the conversion of
phenylalanine to tyrosine.
99. PEDIGREE CHARTING
OBTAINING A PEDIGREE
• A three generation family history should be a
standard component of medical practice. Family
history of the patient is usually summarized in the
form of a pedigree
100. POINTS TO REMEMBER
• ask whether relatives have a similar
problem
1.
• ask if there were siblings who have
died
2.
• inquire about miscarriages, neonatal
deaths
3.
• be aware of siblings with different
parents
4.
• ask about consanguinity
• ask about ethnic origin of family
branches
5.
101. PEDIGREE TERMINOLOGY
• Proband (propositus or index case): is the affected individual through
whom a family with a genetic disorder is first brought to attention.
• Consultand: the person who brings the family to attention by consulting a
geneticist, may be an unaffected/affected relative of the proband.
• Brothers and sisters = sibs, and a family of sibs = sibship
• Kindred = the entire family. Relatives are classified 1st degree, 2nd degree,
etc.
• Consanguineous = couples who have one or more ancestors in common
• Isolated case = if only one affected member in the kindred (= sporadic
case if disorder in propositus is determined to be due to new mutation)
102.
103. APPLICATIONS OF GENETIC
COUNSELING
Genetic counselors work with people concerned about the risk of an inherited
disease or condition. These people represent several different populations
• 1. Prenatal Genetic Counselling: There are several different reasons a person
or couple may seek prenatal genetic counselling. If a woman is of age 35 or
older and pregnant, then there is an increased chance that her fetus may have a
change in the number of chromosomes present. Changes in chromosome
number may lead to mental retardation and birth defects. Prenatal tests that are
offered during genetic counselling include Level II Ultrasound The maternal
serum AFPChorionic Villus sampling (CVS) Amniocentesis.
• 2. Paediatric Genetic Counselling: Families or paediatricians seek genetic
counselling when a child has features of an inherited condition. Any child who
is born with more than one defect, mental retardation or dysmorphic features
has an increased chance of having a genetic syndrome. A common type of
mental retardation in males for which genetic testing is available is fragile X-
syndrome.
104. • 3. Adult Genetic Counselling: Adults may seek genetic
counselling when a person in the family decided to be tested for the
presence of a known genetic condition, when an adult begins
exhibiting symptoms of an inherited condition, or when there is a
new diagnosis of someone with an adult-onset disorder in the
family In addition, the birth of a child with obvious features of a
genetic disease leads to diagnosis of a parent who is more mildly
affected Genetic counselling for adults may lead to the
consideration of presymptomatic genetic testing
• 4. Cancer Genetic Counselling: A family history of early onset
breast, ovarian or colon cancer in multiple generations of family is
a common reason a person would seek a genetic counsellor who
works with people who have cancer. While most cancer is not
inherited, there are some families in which a dominant gene is
present and causing the disease A genetic counsellor is able to
discuss the chances that the cancer in the family is related to a
dominantly inherited gene. The counsellor can also discuss the
option of testing for the breast and ovarian cancer genes.
105. ROLE OF A NURSE IN GENETIC
COUNSELING
• Guiding a women or couple through prenatal
diagnosis.
• Helping parents make decision in regard to abnormal
prenatal diagnostic results.
• Assisting parents who have had a child with a birth
defect to locate needed service and support.
• Providing support to help the family deal with the
emotional impact of a birth defect.
• Coordinative services of other professionals, such as
social workers, physical and occupational therapist,
psychologist & dietician.
106. TERATOLOGY
• Teratology is a specialized area of embryology. It is the study
of the etiology of abnormal development (the study of birth
defects). Developmental toxicity any morphological or
functional alteration caused by chemical or physical insult that
interferes with normal growth, homeostasis, development,
differentiation, and/or behaviour.
• Teratogens therefore are xenobiotics and other factors that
cause malformations in the developing conceptus. Examples
of teratogens may include pharmaceutic compounds,
substances of abuse, hormones found in contraceptive agents,
cigarette components, and heavy metals. viral agents, altered
metabolic states induced by stress, and nutrient deficiencies
(e.g., folic acid deficiency).
107. PRINCIPLES OF TERATOLOGY
1. Susceptibility to teratogenesis depends on the embryo’s
genotype that interacts with adverse environmental
factors (G × E interaction)
2. The developmental stage of conceptus to the exposure
determines the outcome.
3. Teratogenic agents have specific mechanisms through
which they exert there pathogenic effects.
4. The nature of the teratogenic compound or factor
determines its access to the developing
conceptus/tissue.
5. The four major categories of manifestations of altered
development are death, malformation, growth
retardation, and functional deficits.
6. The manifestations of the altered development increase
with increasing dose.
109. CRITICAL PERIODS
• Major fetal outcomes depend on the stage of pregnancy affected, as
there are critical periods for the development of fetal processes and
organs.
• One may divide the developmental stages in to three large
categories: pre-implantation, implantation to organogenesis, and the
fetal to neonatal stage.
• The outcomes associated with exposure during these periods vary.
STAGE OF EXPOSURE OUTCOMES
PRE-IMPLANTATION EMBRYONIC LETHALITY
IMPLANTATION TO TIME OF
ORGANOGENESIS
MORPHOLOGICAL DEFECTS
FETAL NEONATAL STAGE FUNCTIONAL DISORDERS, GROWTH
RETARDATION, CARCINOGENESIS
110. SOME WELL KNOWN TERATOGENS
THALIDOMIDE
Thalidomide is a sedative-hypnotic drug used in Europe from
1957 to 1961. It was marketed for morning sickness, nausea,
and insomnia . It went into general use and was widely
prescribed in Europe, Australia, Asia, Africa, and the
Americas.
Women who had taken the drug from gestation days (GD) 35
to 50 gave birth to offspring suffering from a spectrum of
different malformations, mainly amelia (absence of limbs) or
phacomelia (severe shortening of limbs). Other
malformations included: absence of the auricles with
deafness, defects of the muscles of the eye and face, and
malformations of the heart, bowel, uterus, and the
gallbladder.
The compound was withdrawn from the market in 1961 after
about 10,000 cases had occurred.
111. ACCUTANE (ISOTETRINOIN)
Accutane (Isotetrinoin) is a member of a family of drugs
called retinoids , which are related to vitaminA. It is approved
to treat serious forms of acne. These painful and disfiguring
forms of acne do not respond to other acne treatments.
Accutane can cause severe, life-threatening birth defects if the
mother takes the medication during pregnancy.
Even one dose of Accutane can cause major birth defects of
the baby's ears, eyes, face, skull, heart, and brain.
Women of child-bearing potential must have regular
pregnancy tests before, during, and after taking isotretinoin.
Accutane is available only under a special program called
iPLEDGE .
112. DIETHYLSTILBESTROL (DES)
• Diethylstilbestrol (DES) DES is a synthetic estrogen that inhibits
ovulation by affecting release of pituitary gonadotropins.
• Some of its uses include treatment for hypogonadism, and in
some cases of prostate cancer.
• From 1940 to 1970, DES was used to help maintain pregnancy.
• In utero exposure to DES has been associated with abnormal
development of the uterus. It has also been associated with certain
types of tumors. Women who were exposed in utero often
developed vaginal neoplasia, vaginal adenosis, and cervical
erosion.
• Effects were not seen in offspring until they reached puberty.
Clear cell carcinoma of the vagina is a type of adenocarcinoma
found in young women who are exposed to diethylstilbestrol in
utero.
• The reproductive organ of males can also be affected subsequent
to in utero exposure. The outcomes include hypotrophic testes,
poor semen volume and quality.
113. ALCOHOL- “FETALALCHOL SYNDROME”:
Alcohol- “Fetal Alchol Syndrome” FAS is a pattern of mental and
physical defects that develops in some offspring when exposed to
alcohol in utero.
The first trimester is the most susceptible period. Some babies
with alcohol-related birth defects, such as lower birth weight and
body size and neurological impairments, do not have all of the
classic FAS symptoms.
These outcomes are often referred to as fetal alcohol effects (
FAE). In addition to growth retardation, the most common
outcomes of fetal alcohol syndrome include psychomotor
dysfunction and craniofacial anomalies.
Other infrequent outcomes include skeletal malformations such as
deformed ribs and sternum, scoliosis, malformed digits, and
microcephaly.
Visceral deformities may also be present: heart defects, genital
malformations, kidney, and urinary defects. A common concurrent
manifestation of FAS include irregular arrangement of neurons
and connective tissue.
