intro abt genetics
TRANSCRIPT
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INTRODUCTION ABOUT GENETICS
Termed coined by william bateson in1906.
DefinitionThe scientific study of the mechanism of inheritance by
which characters pass from parents to offspring.
Brief History
First there was Gregor Mendel, a monk (1822-1884) who studiedinherited characteristics.
IN1866
Gregor Mendel published the results of his investigations of the
inheritance of "factors" in pea plants.
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IN 1950
Rosalind Franklin, H. C. Crickand James; D. Watson Discover
chemical structure of DNA starting a new branch of science -molecular
Genetics.
TERMS RELATED TO GENETICS
Molecular genetics: Study of structure and function ofchromosomes
Heredity: Transmission of characteristics from parents tooffspring.
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Trait: Two contrasting choices.
Genotype :Genetic make up of organism(TT ;T t ;t t )
Phenotype : What is physically observed(tall, short )
Heterozygous: Two different alleles Dominant traits: Characteristics that when present is always
expressed.
Recessive traits: Masked by dominant trait; only appears if thereare two copies.
Allele: Each alternative for a gene; occurs in pairs.
CHROMOSOME
Any several thread like bodies, consisting of chromatin, found in acell nucleus that carry the genes.
KARYOTYPE
It is the number and appearance of chromosome in the nucleus ofcell.
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GENE :Individual factors that don't blend with one another, control
traits in living things.
The basic unit of genetic information
They determine the nature and the function of the cell.
The human genes (about 120,000) are referred to as the human
genome. A genome is the full set of genes in each cell of an organism.
MUTATION:It is a rare, inheritable variation in the amount or the
structure of genetic material in the genotype of the individual.
Two types of mutation: Chromosomal mutations
Gene mutations
CHROMOSOMAL MUTATIONS
Two type:
Intrachromosomal modificationsInterchromosomal modifications
INTRACHROMOSOMAL MODIFICATIONS
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INTERCHROMOSOMAL MODIFICATIONS
GENE MUTATION
MUTON:The smallest portion of gene on which mutation takeplace.
TYPES OF GENE MUTATION Transitions
Transversions
Deletions
Insertions
PEDIGREE ANALYSISA kind of genetic analysis in which
a trait is traced through several generations of a family to determined
how the trait is inherited.
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CLINICAL GENETICSA branch of genetics which deals with the
diagnosis of genetics diseases, care and counseling of patient with
genetic disorder.
DEFINITION OF GENETIC DISORDER:A disease or disorder that is inherited genetically
or
A genetic disorder is an illness caused by abnormalities in genes or
chromosomes. While some diseases, such as cancer, are due in part
to a genetic disorder, they can also be caused by environmental
factors.
Factors increased risk of genetic disorders:
Maternal Age:Women is 30 years old .Some researchers believethat errors can crop up in the eggs' genetic material as they age
over time.
Therefore, older women are more at risk of
giving birth to babies with chromosome abnormalities thanyounger women. Since men produce new sperm throughout their
life, paternal age does not increase risk of chromosome
abnormalities.
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Environment:Although there is no conclusive evidence that
specific environmental factors cause chromosome abnormalities, it
is still a possibility that the environment may play a role in the
occurrence of genetic errors.
Parents who have a genetic disease
A family history of a genetic disease
Parents who do not show disease symptoms, but "carry" a
disease gene in their genetic makeup (this can be discovered
through genetic testing)
TYPES OF GENETIC DISORDERS
Gene disorders
Chromosomal disorders
Multifactorial disorders
Mitochondrial disorders
GENE DISORDERS
Autosomal dominant
Autosomal recessive
X-linked dominant
x-linked recessive
Y-linked
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Autosomal dominant
By definition
Genes that are situated on chromosomes other thanthe X or Y (sex chromosomes) are autosomal.
Autosomal dominant characteristic features:
An affected individual usually bears an equal number of affected
and unaffected offspring.
Males and females are affected in equal numbers.
Each gender can transmit the trait to male and female.
Normal children of an affected individual have only normal
offspring.
AUTOSOMAL DOMINANT DISEASES
POLYDACTYLY ACHOO SYNDROME
HUNTINGTONS DISEASE
ACHONDROPLASTIC DWARFISM
POLYDACTYLY, SYNDACTYLY
DEFINITION:
Polydactyl: a congenital abnormality, is thepresence of more than the normal number of fingers or toes.
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Syndactyly: is the webbing or fusing together of two or morefingers or toes. It varies in degree of severity from incomplete
webbing of the skin of two digits to complete union of digits and
fusion of the bones and nails
Treatmentonly surgery
ACHOO SYNDROME.
DEFINITION:Anautosomal dominanthereditary trait which causes
sneezing (due to naso-ocular reflex) when suddenly exposed to
bright light
Mechanism The cause is congenital malfunction innerve signals in the
trigeminal nerve nuclei.The fifthcranial nerve,called the
trigeminal nerve, is apparently responsible for sneezes. Some
people have an association between this nerve and the nerve that
transmits visual impulses to the brain. Overstimulation of theoptic
nerve triggers thetrigeminal nerve,and this causes the photic
sneeze reflex.
Diagnosis Simply by observing the sneezing pattern of a person, If the person
seems to sneeze every time they are exposed to a bright light, and
http://en.wikipedia.org/wiki/Autosomal_dominanthttp://en.wikipedia.org/wiki/Heredityhttp://en.wikipedia.org/wiki/Sneezehttp://en.wikipedia.org/wiki/Nervehttp://en.wikipedia.org/wiki/Trigeminal_nerve_nucleihttp://en.wikipedia.org/wiki/Cranial_nervehttp://en.wikipedia.org/wiki/Optic_nervehttp://en.wikipedia.org/wiki/Optic_nervehttp://en.wikipedia.org/wiki/Trigeminal_nervehttp://en.wikipedia.org/wiki/Trigeminal_nervehttp://en.wikipedia.org/wiki/Optic_nervehttp://en.wikipedia.org/wiki/Optic_nervehttp://en.wikipedia.org/wiki/Cranial_nervehttp://en.wikipedia.org/wiki/Trigeminal_nerve_nucleihttp://en.wikipedia.org/wiki/Nervehttp://en.wikipedia.org/wiki/Sneezehttp://en.wikipedia.org/wiki/Heredityhttp://en.wikipedia.org/wiki/Autosomal_dominant -
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if their parents and offspring do the same, then the diagnosis of the
ACHOO syndrome can be made.
Currently, there are no known blood tests or other medical tests
that can help diagnose the syndrome.
ManagementAntihistamines used to treat seasonal allergies may also reduce
the occurrence of solar sneezes in people affected by both
conditions
HUNTINGTONS DISEASE
DEFINITION:Huntington's disease (HD) is an inherited,
degenerative brain disorder which results in an eventual loss of
both mental and physical control.
The disease is also known as
Huntington's chorea.( Chorea means "dance-like movements" and
refers to the uncontrolled motions often associated with the
disease.)
Person gradually loses psychomotor control in adulthoodDifficulties in chewing, swallowing and speaking.
Male
Hh
Female
hh
eggs
sperm
Alleles
H = Huntingtonh = Normal
Genotypes-Phenotypes
HH -HuntingtonHh - Huntington
hh- normal
Each child would
have a __% chance
of having
Huntington Disease
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H
h
h h
Hh
hh hh
HhMale
Hh
Female
hh
eggs
sperm
Alleles
H = Huntington
h = Normal
Genotypes-Phenotypes
HH - Huntington
Hh - Huntington
hh - normal
Each child would
have a 50% chance
of having
Huntington Disease
TreatmentChemical structure of tetrabenzine, an approved compound for the
management of chorea in Huntingtons disease.
There is no cure for, Huntingtons disease
but there are treatments available to reduce the severity of some of its
symptoms
ACHONDROPLASTIC DWARFISM
DFINITION:Achondroplastic dwarfs have short stature, with an
average adult height of 131 cm (4 feet, 3 inches) for males and 123 cm
(4 feet, inch) for females.
Achondroplastic dwarfism occurs as a mutation in
approximately 85% of cases (associated with advanced paternal age) or
may be inherited in an autosomal dominant genetic disorder that is acommon cause of dwarfism.
The prevalence is approximately 1 in 25,000.
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The word achondroplasia literally means "without cartilage formation."
However, the problem is not in forming
cartilage but in converting it to bone (a process called ossification),particularly in the long bones of the arms and legs.
Cause of achondroplasiaAutosomal dominant mutation in the fibroblast growth
factor receptor gene 3 (FGFR3), which causes an abnormality of
cartilage formation.
In normal circumstances, FGFR3 has a
negative regulatory effect on bone growth. In achondroplasia, the
mutated form of the receptor is constitutively active and this leads
to severely shortened bones .
Treatment:There is no known treatment for achondroplasia.
Although used by those without achondroplasia to aid in growth,
human growth hormone does not help people with achondroplasia.
However, if desired, the controversial surgery of limb-lengthening
will lengthen the legs and arms of someone with achondroplasia.
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AUTOSOMAL RECESSIVE:
By Definition:
Autosomal recessive conditions are clinicallyapparent only in the homozygous statewhen both alleles at a particular
genetic locus are deleterious
Characteristics of autosomal recessive disorder On average, male and female siblings are affected in equal
proportions;
The parents are clinically normal;
On average, half of the children are affected when an affected
individual mates with a heterozygous carrier (a pseudo-dominantpedigree)
On average, if both parents are heterozygous at the same
genetic locus, one-fourth of their children are homozygous
affected, one-fourth are homozygous normal, and half are
heterozygous carriers of the same mutant gene.
AUTOSOMAL RECESSIVE DISEASES
TAY SACHS DISEASES
CYSTIC FIBRISIS
SICKLE CELL ANAEMIA
ALBINISM
PHENYLKETOUREA
GALACTOSEMIA
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Tay-sachs disease
Multiple kinds of mutation on Chromosome 15
Signs:Characteristic features include muscle weakness, loss of muscle
coordination (ataxia) and other problems with movement, speech
problems, and mental illness
Cause: Problem in HEXA gene which provides instructions for making
part of an enzyme called beta-hexosaminidase A, which plays a
critical role in the brain and spinal cord. This enzyme is located in
lysosomes, which are structures in cells that break down toxic
substances and act as recycling centers. Within lysosomes, beta-
hexosaminidase A helps break down a fatty substance called GM2
ganglioside.
accumulation of lipids on brain
Central nervous system degrades
brain malfunction; death by age 5
Sickle cell anemiaSickle cell anemia is a serious disorder in which the body makes sickle-
shaped red blood cells. Sickle-shaped means that the red blood cells
are shaped like a crescent
Red blood cells are disc-shaped without holes in the center. They
move easily through your blood vessels.
Sickle cells cells don't move easily through your blood vessels.
They're stiff and sticky and tend to form clumps and get stuck inthe blood vessels.
The clumps of sickle cells block blood flow in the blood
vessels in the limbs and organs. Blocked blood vessels can cause pain,
serious infections, and organ damage.
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Normal red blood cells live about 120 days in the bloodstream and
then die. In sickle cell anemia, the number of red blood cells is low
because sickle cells don't last very long. Sickle cells usually die
after only about 10 to 20 days
Symptoms ischemia, pain, necrosis and often organ damage.
Alleles
N = Normal
n = Sickle Cell
Male
NN
Female
Nn
eggs
sperm
Genotypes-Phenotypes
NN - Normal
Nn - Sickle Cell Trait
nn - Sickle Cell Anemia
Each child would
have a __% chance
of having Sickle
Cell Trait
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Alleles
N = Normal
n = Sickle Cell
N
N
N n
Nn
NN Nn
NNMale
NN
FemaleNn
eggs
sperm
Genotypes-Phenotypes
NN - Normal
Nn - Sickle Cell Trait
nn - Sickle Cell Anemia
Each child would
have a 50% chance
of having Sickle
Cell trait
Pathophysiology
Sickle-cell anemia is caused by a point mutation in the -globin
chain of hemoglobin, causing the hydrophilic amino acid glutamic
acid to be replaced with the hydrophobic amino acid valine at thesixth position. The -globin gene is found on the short arm of
chromosome 11
In normal Hemoglobin A, glutamic acid is on the 6th position of
the beta chain, while in sickle-cell disease, this glutamic acid is
replaced by valine leading to the formation of sickle cells .
Management
Folic acid and penicillin
Analgesics
blood transfusion
Bone marrow transplants
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Cystic fibrosis
Cystic fibrosis is caused by a mutation in the gene for the protein cystic
fibrosis transmembrane conductance regulator (CFTR). This gene isrequired to regulate the components of sweat, digestive juices, and
mucus.
The CFTR gene, found at the q of chromosome 7.
Clinical manifestations
clubbing of the fingers
Frequent chest infections and coughing or shortness of breath.
Mucus in the paranasal sinuses causes facial pain, fever, nasal
drainage, and headaches.
Thickened secretions from the pancreas, an organ responsible for
providing digestive juices which help break down food
Treatment
Proactive treatment of airway infection
Antibiotics such as vancomycin, tobramycin, ciprofloxacin.
Lung transplantation often becomes necessary for
individuals with cystic fibrosis as lung
Gene therapy.
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Albinism
Lack of pigment in skin, hair, and eyes.
Approx. 1 in 17,000 peopleDangers:
Eye problems
Severe sensitivity to sunburn
Phenylketonuria (PKU)Phenylketonuria (PKU) is an autosomal recessive metabolic disorder
characterized by a deficiency in the hepatic enzyme phenylalanine
hydroxylase (PAH).
This enzyme is necessary to metabolize the amino acid
phenylalanine to the amino acid tyrosine. When PAH is deficient,
phenylalanine accumulates and is converted into phenylpyruvate
(also known as phenylketone), which is detected in the urine.
Phenylalanine is an essential amino acid and is found in nearly all
foods which contain protein, dairy products, nuts, beans etc.
A low protein diet must be followed.
Brain damage can result if the diet is not followed causing mentalretardationand mousy body odor (phenyl acetic acid is in sweat).
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SEX LINKED DISORDERSGenes are on sex chromosome.
There are 2 functions of sex chromosomes: sex determination and
control of some metabolic activities.
In females, only 1 X chromosome remains active and other
remains inactive.
X-linked dominant diseasesBoth sexes are affected.
Males are severely affected.
If father carries abnormal X gene, all daughters will inherit the
disease and sons are normal.
Affected heterozygous females transmit these disorders to maleand female children equally; half of their children will inherit the
disease tendency.
Hypophosphatemic rickets
It is an X-linked dominant form of rickets that differs from most cases of
rickets in that ingestion of vitamin D is relatively ineffective.
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It can cause bone deformity including short stature. It is
associated with a mutation in gene sequence (Xp.22) and subsequent
inactivity of protein.
The prevalence of the disease is 1:20000.
The mutation results in altered (or missing) activity of the PHEXprotein, which inactivates hormone-like substances
(phosphatonins) that promote phosphate excretion. The resulting
excess excretion of phosphate impairs bone mineralization
X-LINKED RECESSIVE
oMales are mostly affected.
oBoth matching genes be abnormal for disease
o
Rarely in females e.g. Turner syndromeoMay skip a generation
oTrait may be transmitted through a series of female
carriers
HemophiliaHemophilia is the oldest known hereditary bleeding disorder.
Caused by a recessive gene on the X chromosome.There are about 20,000 hemophilia patients.
One can bleed to death with small cuts
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A disorder in which a persons blood does not clot properly.
Gene found on X chromosome.
1 in 10,000 males born are afflicted
Symptoms
Bleeding into joints, with associated pain and swelling Blood in the urine or stool
Gastrointestinal tract and urinary tract hemorrhage
Nosebleeds
Prolonged bleeding from cuts, tooth extraction, and surgery
Spontaneous bleeding
COLOUR BLINDNESS
Color blindness or color vision deficiency is the decreased ability to
perceive differences between some of the colors.
Color blindness originate from at least 19
different chromosomes and 56 different genes t others can distinguish.
Management
There is generally no treatment to cure color deficiencies.
However, certain types of tinted filters and contact lenses
may help an individual to better distinguish different
colors.
Optometrists can supply a singular red-tint contact lens to
wear on the non-dominant eye
Y-LINKED DISEASES
Only males are affected.
Sons of affected male inherit the trait
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HAIRY EARS
Y-linked trait, which are rare
Symptomshairy earsOnly 1 cure known.
MULTIFACTORIAL DISORDERS
Multifactorial traits result from the interaction of one or more
environmental factors and two or more genes. Genetic disorders may also be complex, multifactorial, or
polygenic, meaning that they are likely associated with the effects
of multiple genes in combination with lifestyle and environmental
factors. Multifactorial disorders include
Multifactorial disorders include
Essential hypertension
Congenital heart diseases
Diabetes mellitus Cleft lip
Spina bifida
Schizophrenia
Peptic ulcer
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Diabetes
Disease in which the body doesnot produce or properly use insulin.
Insulin is a hormone that is needed to convert sugar, starches, and otherfood into energy needed for daily life.
Genetic mutation can lead to Type 1 diabetes, but no one sure if
relative to a specific gene
Type 1 reveals itself in childhood, Type 2 can be made worse from
excessive lifestyle
Warning signs
Extreme thirst
Blurry vision from time to time
Frequent urination Unusual fatigue or drowsiness
Unexplained weight loss
Diabetes is the leading cause of kidney failure, blindness, and
amputation in adults, and can also lead to heart disease.
MITOCHONDRIAL DISORDERSMitochondrial diseases are a group of disorders caused by
dysfunctional mitochondria, the organelles that are the "powerhouses"found in most eukaryotic cells. Mitochondria convert the energy of food
molecules into the ATP that powers most cell functions.
Characteristics
The effects of mitochondrial disease can be quite varied.
Since the distribution of the defective mitochondrial DNA may
vary from organ to organ within the body, and each mutation is
modulated by other genome variants, the mutation that in oneindividual may cause liver disease might in another person cause a
brain disorder.
The severity of the specific defect may also be great or small.
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Most common mitochondrial disorders:
Lever's hereditary optic atrophy (eye disease),
A type of epilepsy called MERRF (myoclonus epilepsy)
congenital lactic acidosis, A type of dementia called MELAS (mitochondrial
encephalopathy)
Treatment Although research is ongoing, treatment options are currently
limited; vitamins are frequently prescribed, though the evidence
for their effectiveness is limited.
Pyruvate has been proposed recently as a treatment option.
CHROMOSOMAL DISORDERS
Children with chromosome abnormalities are born with an
irregular number of chromosomes (more than or fewer than 46) or
with one or more chromosomes that have irregular structures
(deletions from or duplications to parts of an individual
chromosome, or with a part of one chromosome moved to another
location).
TYPES AUTOSOMAL
TRISOMY
MONOSOMY
SEX LINKED
MONOSOMY TRISOMY
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AUTOSOMAL DISORDERS
TRISOMY:A condition in which extra chromosomes are present.
Monosomy:A condition in which chromosomes are absent.
Related to trisomy of chromosomes:
Down syndrome(21)
Edwards syndrome (18)
Patau syndrome (13),
Trisomy 22/Cat eye syndrome (22)
Trisomy 16
Related to monosomy of chromosome
Wolf- Hirschhorn syndrome
Cri du chat
Williams syndrome
Jacobsen syndrome
Angel man syndrome
18q deletion syndrome
Related to trisomy of chromosomes:
Down syndrome(21)This means that the individual has a trisomy (32lst chromosomes
Symptoms
Short, broad hands
Stubby fingers
Rough skin
Upward slant to eyes.
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Mentally retarded
Small round face, flat nose.
Protruding tongue
Short neck
CAUSE:Chances of having a baby with Down Syndrome increaseswith the age of the mother.
Trisomy 18 or Edward's Syndrome
Trisomy 18, or Edward's syndrome, is the second most common trisomy
after Down's syndrome. Edward's syndrome occurs when three sets
(trisomy) of chromosome 18 occur.
Trisomy 18 is therefore caused by a geneticabnormality occurring before conception, when egg and sperm cells are
made. A healthy egg or sperm cell contains 23 individual chromosomes
- one to contribute to each of the 23 pairs of chromosomes needed to
form a healthy, 46 chromosome cell. However, sometimes egg and
sperm cells are left with 24 (or more) chromosomes. It is the joining of
these egg or sperm cells .
Sign and symptoms:
Children born with Edwards' syndrome appear weak and fragile,
and they are often underweight.
The head is unusually small and the back of the head is prominent.
The ears are malformed and low-set, and the mouth and jaw are
small (also known as micrognathia).
The baby may also have a cleft lip.
Often, the hands malformed, clenched into fists with the index
finger overlapping the other fingers.
The child may have club feet, and toes may be webbed or fused.
A number of problems involving the internal organs may be
present.
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Treatment
There is no cure for Edwardsssyndrome. Ninety to 95 %
of all babies born with it die within a year of birth. The few infants
that do survive need special treatment--ranging from muscular
therapy to nervous system and skeletal corrections--for theirvarious handicaps.
Related to monosomy of chromosome:
Cri du chat syndromeCri du chat syndrome - also known as 5p- syndrome and cat cry
syndrome - is a rare genetic condition that is caused by the deletion (a
missing piece) of genetic material on the small arm (the p arm) of
chromosome 5.
Cause
The cause of this rare chromosomal deletion is unknown.
Clinical symptoms
High-pitched cat-like cry,
Mental retardation, Small head size (microcephaly),
Widely-spaced eyes (hypertelorism)
low birth weight and weak
muscle tone (hypotonia) in infancy. The cat-like cry typically
becomes less apparent with time.
Difficulty with language.
Feeding difficulties
SEX LINKED MONOSOMY DISORDERS
Turners syndrome:
In females, a person only inherits one X chromosome (45,X)
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Occurs in about 1 of 10,000 females.
One of the X chromosomes is either missing or inactive.
Signs;
These women have immature female appearance, donot develop secondary sex characteristics, and lack internal
reproductive organs.
Turner syndrome is associated with underdeveloped ovaries, short
stature, webbed, and is only in women.
Bull neck, and broad chest. Individuals are sterile, and lack
expected secondary sexual characteristics.
Mental retardation typically not evident
SEX LINKED TRISOMY DISORDERS KLINEFELTERS SYNDROME
XYY SYNDROME
SUPER FEMALES
KLINEFELTERS SYNDROME(XXY,XXYY)Disorder occurring due to nondisjunction of the X chromosome.The
Sperm containing both X and Y combines with an egg containing the X,results in a male child. The egg may contribute the extra X
chromosome.
SIGNS
Males with some development of breast tissue normally seen in
females.
Little body hair is present, and such person are typically tall, have
small testes.
Infertility results from absent sperm. Evidence of mental retardation may or may not be present.
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XYY SYNDROMEOccurs in about 1 0f 1,000 males. The men tend to be taller than
average, with a greater incidence of acne and minor skeletal
abnormalities.
SIGNS :
Height usually 6 feet or over.
Personality disorder
Behavioural disturbances
3- Superfemale Syndrome (XXX, XXXX, XXXXX)Occurs in about 1 of 1,000 females. Women appear normal, but tend to
score slightly below average in intelligence.Congenital abnormalitieslike underdeveloped
external genitalia,uterus and vagina.
DIAGNOSTIC APPROACH OF GENETIC
DISORDERS
Sample used: Blood
Skin
Hair
Different kind of cells
Biochemical and enzyme analysis
Chromosomal and gene analysis
TREATMENT OF GENETIC DISORDERSMost genetic disorders couldntbe cured.
Better care from family
Better welfare of the society.
Function training
Gene therapy
Bone marrow transplantation.
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