Genes Genes are the units of heredity. They contain the hereditary information encoded in their chemical structure for transmission from generation to.

Genes

• Genes are the units of heredity. They contain the hereditary information encoded in their chemical structure for transmission from generation to generation. They affect development and function, both normal and abnormal.

Genotypes

• Since genes are contained in the chromosomes, genes also occur in pairs. If the genes comprising a pair are alike (AA), the individual is described as homozygous for that gene.

• And if it is different (Aa) the individual is described as heterozygous.

Mutation

• Genes are usually stable, but sometimes normal genes may be converted into abnormal ones - this change is called mutation. Mutation is a regular phenomenon in nature.

• The natural mutation rate is increased by exposure to mutagens such as ultraviolet rays, radiation or chemical carcinogens.

Genotype

• The term genotype refers to the total genetic constitution of an individual But the genotype is relatively stable throughout the life of an individual. Thus there are two aspects of the genetic material -one fixed and the other plastic.

Phenotype

• The term phenotype refers to the outward expression of the genetic constitution.

• Certain phenotype characteristics of an individual may change from infancy to adulthood such as height, weight, muscularity, body shape, The fixed characters are the genotype and the plastic ones are the phenotype.

Chromosomal abnormalities

• Aneuploidy• Translocation• Deletion• Duplication• Inversion• Isochrqmosomes• Mosaicism

Classification of genetic disorders

• These may be classified as

a. Chromosomal abnormalitiesb. Unifactorial (single gene or Mendelian)

diseasesc. Multifactorial disorders

CHROMOSOMAL DISORDERS

• More than 300 numerical and structural types of chromosome aberrations have been described. A significant portion of embryonic and foetal wastage is due to chromosomal anomalies. The incidence of chromosomal abnormalities is 5.6 per 1000 live births.

Klinefelter's Syndrome

• This is a common sex -chromosome aneuploidy persons suffering from this syndrome are abnormal males having two or more X chromosomes in addition to one Y-chromosome (XXY, XXXY). They have a normal autosomal set of 22. The main features of this syndrome are that the affected persons are eunuchoid males with non-functional testis.

XYY Syndrome

• The male with an extra Y chromosome has attracted much attention because of his reported tendency to anti-social, aggressive and often criminal behavior. However, the relationship is not yet clear. The principal features of this syndrome appear to be exceptional height (usually six feet and over) and a serious personality disorder leading to behavioural disturbances. The incidence of this syndrome is about 1 in 1000 males at birth.

Turner's Syndrome

• Persons suffering from this syndrome are apparent females with underdeveloped sex glands. They have 45 chromosomes instead of the normal complement of 46.

• Clinically the patients are of short stature, infertile and have primary amenorrhoea. They often show other congenital defects such as coarctation of the aorta, pulmonary stenosis, renal malformations and mental retardation.

• "Super Females" : Females with 3 to 5 X-chromosomes (XXX, XXXX, XXXXX) have beenfound. In general, the higher the number of X-chromosomes, the greater the degree of mental retardation and congenital abnormalities, e.g., underdeveloped external genitalia, uterus and vagina.

2. Relating to autosomes :

• There are many syndromes associated with abnormalities of autosomes. mongolism is a public health problem in some countries,

• Most cases of mongolism are caused by an extra chromosome which occurs on the 21st pair.

mongolism

• The anomaly is therefore sometimes described as "Trisomy 21". The syndrome is easily recognised in the older child and adult by the short stature and small round head, narrow, tilted eye-slits, mal-formed ears, short broad hands, lax limbs, mental retardation and quite a few other abnormalities especially internal congenital defects such as cardiac defects and atresia of the alimentary tract. In communities of European origin the incidence of mongolism at birth is reported to be one in 900 births.

mongolism

• One observation which is important is that the frequency of mongolism increases with rising maternal age but is un-affected by the age of the father. The risk for a woman of 20 is estimated at about \ in 3,000 and that for a woman of 45, 1 in 50.

"point" mutation

• Mendelian diseases are individually rare since there is strong selection against them and gene mutations are rare events. Mutation usually occurs at random. If mutation is confined to a single gene it is called "point" mutation, which is responsible for many human diseases and defects.

• Blood groups

• ABO SYSTEM

• RHESUS SYSTEM

• Erythroblastosis foetalis

• Blood groups and disease

Sickle cell anemia

• Sickle cell anaemia is an autosomal recessive disorder in which an abnormal haemoglobin leads to chronic haemolytic anaemia with a variety of severe clinical consequences. The disorder is a classic example of disease caused by a point mutation in DNA. Individuals with one gene of this disease are clinically healthy, but their RBC look abnormal under the microscope..

Thalassemias:

• The thalassemias are hereditary disorders characterized by reduction in the synthesis of globin chain (alpha or beta). Reduced globin chain synthesis causes reduced haemoglobin synthesis and eventually produces a hypo chromic microcytic anaemia because of defective haemoglobinization of red cells. Thalassemias can be considered among hypo-proliferate anemia's, the hemolytic anemia's, and the anaemias related to abnormal haemoglobin, since all of these factors may play a role.

• Haemophilia

• Cystic fibrosis

• Phenylketonuria

MULTIFACTORIAL DISORDERS

• Role of genetic predisposition in common disorders:

• Cancer

• Coronary heart disease

• Diabetes

• Mental Disorders

Advances in molecular genetics

• DNA technology

• Gene Therapy

• The Human Genome Project

• The Human Genome Diversity Project

PREVENTIVE AND SOCIAL MEASURES

• EUGENICS : Galton proposed the term eugenics for the science which aims to improve the genetic endowment of human population. Eugenics has both negative and positive aspects.

• EuTHENICS :

• Mere improvement of the genotype is of no use unless the improved genotype is given access to a suitable environment, an environment which will enable the genes to express themselves readily.

• (c ) GENETIC COUNSELLING

• (i) Prospective genetic counseling

• (ii) Retrospective genetic counseling

• OTHER—GENETIC PREVENTIVE MEASURES– Consanguinous marriages– Late marriages

Specific protection

• Increasing attention is now being paid to the protection of individuals and whole communities against mutagens such as X-rays and other ionizing radiations and also chemical mutagens. Patients undergoing X-ray examination should be protected against unnecessary exposure of the gonads to radiation. X-ray examination of the pregnant uterus to determine the presence of twins or the lie of the foetus is to be strongly deprecated. Rh haemolytic disease of the newborn which is a genetically determined immunological disorder is now preventable by immunization by anti- D globulin.

Early diagnosis and treatment

• Detection of genetic carriers

• Prenatal diagnosis

Amniocentesis• Amniocentesis is called for in the following

circumstances ifthe parents are prepared to consider abortion.

• 1. A mother aged 35 years or more (because of high risk of Down's syndrome with advanced maternal age).

• 2. Patients who have had a child with Down's syndrome or other chromosomal anomalies.

• 3. Parents who are known to have chromosomal translocation.

• 4. Parents who have had a child with a metabolic defect -detectable by amniocentesis. The most common are defects of the neural tube, anencephaly and spina bifida which can be detected by an elevation of alpha fetoprotein in the amniotic fluid.

• 5. When determination of the sex is warranted, given a family history of a sex-linked genetic disease e.g., certain muscular dystrophies.

• c) Screening of newborn infants • Recognizing preclinical cases

Rehabilitation

• Finally, rehabilitation. With many genetic or partially genetic conditions causing physical or mental disability, much can be done for the patient and for his family in helping him to lead a better and more useful life.

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