Intro Abt Genetics

8/21/2019 Intro Abt Genetics

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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
http://en.wikipedia.org/wiki/Antihistaminehttp://en.wikipedia.org/wiki/Antihistamine


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H

h

h h

Hh

hh hh

HhMale

Hh

Female

hh

eggs

sperm

Alleles

H = Huntington

h = Normal


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


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


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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Documents

Intro Abt Genetics