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click here for freelancing tutoring sitesINTRODUCTION ABOUT GENETICS

Termed coined by william bateson in1906.Definition

The 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 studied

inherited characteristics.

IN1866 Gregor Mendel published the results of his investigations of the inheritance of "factors" in pea plants.

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 of

chromosomes• Heredity: Transmission of characteristics from parents to

offspring. 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 allelesDominant traits : Characteristics that when present is always

expressed.

Recessive traits : Masked by dominant trait; only appears if there are two copies.

Allele : Each alternative for a gene; occurs in pairs.

CHROMOSOMEAny several thread like bodies, consisting of chromatin, found in a cell nucleus that carry the genes.

KARYOTYPE• It is the number and appearance of chromosome in the nucleus of

cell.

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 modifications Interchromosomal modifications

INTRACHROMOSOMAL MODIFICATIONS

INTERCHROMOSOMAL MODIFICATIONS

GENE MUTATION

MUTON : The smallest portion of gene on which mutation take place.

TYPES OF GENE MUTATION Transitions Transversions Deletions Insertions

PEDIGREE ANALYSIS A kind of genetic analysis in which a trait is traced through several generations of a family to determined how the trait is inherited.

CLINICAL GENETICS A 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 orA 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 believe that 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 than younger women. Since men produce new sperm throughout their life, paternal age does not increase risk of chromosome abnormalities.

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 dominantAutosomal recessiveX-linked dominantx-linked recessiveY-linked

Autosomal dominant

By definition Genes that are situated on chromosomes other than the 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• HUNTINGTON’S DISEASE• ACHONDROPLASTIC DWARFISM

POLYDACTYLY, SYNDACTYLY

DEFINITION: Polydactyl : a congenital abnormality, is the presence of more than the normal number of fingers or toes.

Syndactyly : is the webbing or fusing together of two or more fingers 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

Treatment –only surgery

ACHOO SYNDROME. DEFINITION:

An autosomal dominant hereditary trait which causes sneezing (due to naso-ocular reflex) when suddenly exposed to bright light

Mechanism The cause is congenital malfunction in nerve signals in the

trigeminal nerve nuclei. The fifth cranial 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 the optic nerve triggers the trigeminal 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

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

HUNTINGTON’S 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 adulthood Difficulties in chewing, swallowing and speaking.

TreatmentChemical structure of tetrabenzine, an approved compound for the management of chorea in Huntington’s disease.

There is no cure for, Huntington’s 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, 3½ inches) for males and 123 cm (4 feet, ½ 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 a common cause of dwarfism.

• The prevalence is approximately 1 in 25,000.

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 achondroplasia Autosomal 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.

AUTOSOMAL RECESSIVE:

By Definition: Autosomal recessive conditions are clinically apparent only in the homozygous state—when 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-dominant pedigree) 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

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 in the 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.

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.

Pathophysiology

Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position. The β-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

Cystic fibrosis

Cystic fibrosis is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). This gene is required 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.

Albinism

Lack of pigment in skin, hair, and eyes.Approx. 1 in 17,000 peopleDangers:

Eye problemsSevere 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 mental

retardation…and mousy body odor (phenyl acetic acid is in sweat).

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 diseases Both 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 male

and 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.

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 PHEX

protein, which inactivates hormone-like substances (phosphatonins) that promote phosphate excretion. The resulting excess excretion of phosphate impairs bone mineralization

X-LINKED RECESSIVEo Males are mostly affected.o Both matching genes be abnormal for disease o Rarely in females e.g. Turner syndromeo May skip a generationo Trait may be transmitted through a series of female

carriers

Hemophilia Hemophilia 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

A disorder in which a person’s 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

HAIRY EARS

Y-linked trait, which are rareSymptoms…hairy 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

Diabetes

Disease in which the body doesnot produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches, and other food 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 one individual may cause liver disease might in another person cause a brain disorder.

The severity of the specific defect may also be great or small.

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

AUTOSOMAL DISORDERSTRISOMY: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 syndromeJacobsen syndromeAngel man syndrome18q deletion syndrome

Related to trisomy of chromosomes:

Down syndrome(21)This means that the individual has a trisomy (3 – 2lst chromosomesSymptoms …

Short, broad hands Stubby fingers Rough skin Upward slant to eyes .

Mentally retarded Small round face, flat nose. Protruding tongue Short neckCAUSE: Chances of having a baby with Down Syndrome increases with 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 genetic abnormality 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.

Treatment

There is no cure for Edwards’s syndrome. 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 their various 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

Turner’s syndrome:

In females, a person only inherits one X chromosome (45,X)

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, do not 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• KLINEFELTER’S SYNDROME• XYY SYNDROME• SUPER FEMALES

KLINEFELTER’S 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.

XYY SYNDROME

Occurs 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 abnormalities like underdevelopedexternal genitalia,uterus and vagina.

DIAGNOSTIC APPROACH OF GENETIC DISORDERSSample used:

Blood Skin Hair Different kind of cells Biochemical and enzyme analysis Chromosomal and gene analysis

TREATMENT OF GENETIC DISORDERS Most genetic disorders couldn’t be cured. Better care from family Better welfare of the society. Function training Gene therapy Bone marrow transplantation.