Fig. 14.1. Symbols used in making pedigree charts.

Human Genetics

Human genetics deals with the inheritance of characters in man. Mostly the facts about human genetics have been collected from the field, or are based upon the genetical studies on other organisms, because human beings are not a very favourable subject for studies of inheritance, due to following reasons:1. Gene expression is very variable because of frequent migration and changes of habitat.2. Hybridisation is a necessary part of genetic experiments, but controlled breeding experiments on human beings in laboratory are impossible and non-ethical.3. Man has a long time difference between two successive generation. A scientist can hardly observe two or three generations of his human subject.4. Most of the human beings are heterozygous for many genes. It is, therefore difficult to find pure-line homozygous strain in human population.

Despite many of the above difficulties, various methods have been utilized to study the genetics of various human traits. Sir Francis Galton recommended two methods to determine human genetic traits and their inheritance- pedigree analysis and twin’s study.

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Fig. 14.3. Histological representation of monozygotic and dizygotic twins.

Pedigree Analysis. A pedigree is a graphical method representing the generation of a particular family with various symbols used for relationships or for a particular trait. Analysis of the pedigree is only possible if both affected and unaffected individuals are shown in the pedigree chart. A member of a family who first comes to the attention of a geneticist is called propositus. The investigator then traces the history of the character found in the propositus back through the history of family and a family tree or pedigree chart is drawn.

How pedigree charts are studied?A pedigree chart has been displayed in figure 14.1.1. Let us study, how to read it, for getting

information about any trait. In the parental generation, father is normal (XY) and mother is affected (X'X'). So, all the sons will be affected (X'Y) and all the daughters will be carriers (XX'). When this affected male is married to a carrier female, 50% of the sons and daughters are affected. Rest of the 50% daughters are carriers.

Twin Studies. In case of human beings, normally a female gives birth to only one young one at a time, but sometimes more than one offspring are born at the same time, known as multiple births. The most commonly observed case of multiple births is the birth of two individuals called as twins. These twins have been found very useful in the study of hereditary traits. These are of two basic types:

(a) Identical Twins. As the name suggests, they have no variability in their traits. They are produced from a single zygote, hence they are also referred to as monozygotic twins. The two blastomeres resulting from the first cleavage of zygote completely separate from each other and develop into independent embryos. These twins belong to the same sex and are similar phenotypically and genotypically. If these are separated and under dissimilar environmental conditions, we can easily determine which of the human variations are genetic and which are somatic. Sometimes, identical twins fail to separate completely from each other, known as siamese twins. They are of help in distinguishing genetic and somatic variations.

(b) Fraternal Twins. Such twins are formed by simultaneous fertilization of two different ova by two different sperms. Since they develop from two different zygotes, they are also called as dizygotic twins. They have different sets of genes and are like normal brothers and sisters, but just happen to grows simultaneously in the same uterus. They may be of same or different sexes. When these are of the same sex, all variations between them at the time of birth must be hereditary because, in the uterus, these have developed in the same environment.

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Fig. 14.4. Amniocentesis technique showing procedure used in detecting the amniotic fluid.

Amniocentesis. It is a technique by which chromosomal abnormality (if any) and sex of the foetus can be easily determined. The method employs the removing amniotic fluid by the help of a hypodermic needle from the amnion surrounding the foetus in the uterus. The amniotic fluid contains some foetal cells which are cultured and are then screened for any genetic disorder. If a disease is detected, abortion of such foetus can be recommended.

GENETIC DISORDERS (by Gene Mutation)

Sickle cell anaemia. It is a blood disease where the red blood cells become sickle shaped as compared to the normal ones. The sickle cells are rigid and exhibit a higher viscosity to flow causing them to accumulate in the blood capillaries. Sickle cell anaemia occurs due to inheritance of a defective allele coding for β-globin. It results in the transformation of Haemoglobin-A into Haemoglobin-S in which glutamic acid is replaced by valine in each of the two β-chains of haemoglobin. The major characteristics of this disease are anaemia, interference in circulation and enlargement of spleen, because sickle cells are accumulated in the spleen for destruction.

Thalassemia. Thalassemia is a group of genetic disorders which results from defective synthesis of subunits of haemoglobin. It is of two types- α-thalassemia and β-thalassemia. In α-thalassemia, out of four genes on 11th chromosome, absence of two genes lead to microcytic and hypochromic erythrocytes without significant anaemia. It is due to gene deletion directly causing reduced α-globin chain synthesis. Death occurs in case of deficiency of all the genes. In β-thalassemia there are two defective genes on 16th

chromosome. It is usually caused by point mutation than large deletions.

Huntington’s chorea. It is caused by a dominant gene mutation on short arm of 4 th chromosome. It is mainly characterized by abnormal speech and respiration, irregular movement of limbs, etc, due to defects in the formation of brain and progressive degeneration of the central nervous system, accompanied by gradual mental and physical deterioration The disease appears after the age of 30.

Marfan’s syndrome. This disease is due to dominant mutation of 15 th chromosome resulting in the production of abnormal connective tissues and extreme looseness of joints. The long bones of body grow longer, fingers are very long called spider fingers or arachnodactyly.

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Fig. 14.5. Mongol.

Cystic fibrosis. It is caused by the mutation in the 7 th chromosome which codes for chloride transport factor (CFTR). The disease is characterized by the production of abnormal glycoprotein in the body, which interferes with the salt metabolism. The sweat in body becomes rich in sodium chloride. Liver functions improperly, due to which fats are not digested normally. One of the principle organ affected by the disease is the pancreas, which develops fibrous growth.

Haemophilia. It is a popular example of sex linked inheritance in human beings, in which the exposed blood does not clot so it is also known as bleeder’s disease. It occurs due to the deficiency of antihaemophilia globulin (haemophilia A) or plamsa thromboplastin (Christmas disease). It is a recessive heterozygous condition and shows criss cross inheritance. In homozygous condition it proves to be fatal.

Phenylketonuria. It is caused by an autosomal homozygous recessive allele, called pp, which fails to produce an enzyme called phenylalanine hydroxylase, which converts phenylalanine to tyrosine. As a result, the concentration of phenylalanine in the body increases. The patients of PKU have light body pigmentation and are physically and mentally retarded, called as phenyl pyruvate idiots.

Albinism. It is caused by a homozygous recessive allele, producing tyrosinase, which catalyses the formation of dihydroxy-phenyl-alanine. This compound is responsible for the formation of dark brown pigment. In its absence melanin formation is stopped, resulting in their deficiency in skin, hairs and iris.

Muscular dystrophy. It occurs due to non synthesis of protein dystrophin which is required in the transmission of nerve impulse. It is characterized by deterioration of muscles at an early age with progressive weakness of muscles, inability to walk around the age of 12, heart irregularities and mental impairment.

Tay Sach’s disease. It is due to the deficiency of acetyl hexosaminidase, which is involved in removing sugar side chains from ceramide. Its absence causes mental retardation due to damaged brain and spinal cord. The damage is due to massive accumulation of ceramide in brain cells. It is a recessive lethal condition.

Night blindness. It causes reduced development of visual pigment, rhodopsin, that interferes with the function of retinal rods. It is a sex linked inheritance, caused by recessive gene carried by X-chromosome. It also occurs due to the deficiency of vitamin A, a type of acquired night blindness.

Colour blindness. A particular trait in human beings renders them unable to differentiate between red and green colour, hence also called as red-green colour blindness. It is also sex linked recessive disorder and shows criss cross inheritance as in haemophilia. Red-green colour blindness is also known as daltonism or proton effect. Red colour blindness is called protanopia, green colour blindness is called deuteranopia, blue colour blindness is called tritanopia.

Philadelphia Chromosome. It involves the deletion of the long arm of chromosome 22. The missing part of this chromosome is translocated to chromosome 9 (reciprocal translocation) and gets attached to it, causing chronic myelogenous leukemia. CML is a type of blood cell cancer. A cellular proto-oncogene called c-abl, usually located on chromosome 9 becomes activated when translocated to chromosome 22.

GENETIC DISORDERS (by Chromosomal Mutation)

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Fig. 14.6. XXY male (Klinefelter’s syndrome).

Fig. 14.7. XO female (Turner’s syndrome)

Down’s syndrome, Mongolism. This is a least severe condition of autosomal trisomy, but most frequent. The affected individuals are mentally retarded, large swollen and protruding tongue, short posture, small and underdeveloped ears, enlarged liver and spleen. In 21 trisomics, the probability of developing leukemia is increased 20 fold. Women above 45 years of age are likely to give birth to a child with Down’s syndrome. Women having hepatitis prior to pregnancy have 3 times more chances to give birth to a Down’s syndrome infant. About 2% patients with Down syndrome have a normal chromosome number of 46. The extra chromosome 21 has been non-reciprocally translocated onto another chromosome of the D or G group. These individuals are referred to as translocation mongols, and, because this condition tends to be hereditary, it is also called familial mongolism.

Klinefelter’s syndrome (XXY). These individuals have the genotype of 44+XXY, i.e. 47 chromosomes. They are genetically males, but their testes are small, underdeveloped and devoid of sperms. They are sterile and show a

tendency to breast development (gynecomastia), and are mildly mentally retarded.

Edward’s syndrome. Because of their severe failure to survive, 18 trisomics have many high abnormalities and death usually occurs within hours or days, but most of the cases end up as spontaneous abortions. They are characterized by severe mental retardation, low set ears, cardiac malformation and is more common in females. It is also related to maternal age.

Patau’s syndrome. Most of the 13-trisomic zygote end up as spontaneous abortions. Individuals with Patau’s syndrome are severely mentally retarded and are often deaf. Various degrees of forebrain defect are common. Eye anomalies range from anopthalmia (absence of eyes)

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to micropthalmia (small eyes). Poldactyly is almost always present. Increased maternal age is a factor of trisomy.

Turner’s syndrome (XO). It is due to the fertilization of an abnormal egg without X chromosome with a X bearing sperm, or due to fertilization of a normal egg with an abnormal sperm devoid of sex chromosome. The zygote resulting from such a fertilization will have a genotype of 44+XO, i.e. 45 chromosomes. They are phenotypic females but their gonads, which appear normal in the embryo, degenerate postnatally. Such ovaries do not produce estrogens and the patient remains sexually infantile. Some common characteristics are webbed neck,, short stature, shield chest and cardiovascular anomaly. They are not severely mentally retarded but their I.Q is below normal.

Super males (XYY). Patients with this chromosome complement show overproduction of testosterone and unusual height. They have a higher probability of coming into conflict with the law than normal males, but their crimes are usually non-violent. Most males lead normal lives and are not distinguishable from normal males, except that they are usually taller, often being 6 ft and above.

Super females (XXX). They are often mentally retarded, and have congenital abnormalities like underdeveloped external genitalia, uterus and vagina. Instead, they are fertile producing normal children.

HUMAN CYTOGENETICS

Genes are the units of heredity. They contain the hereditary information for transmission from generation to generation, and affect the development and function of an individual. The human genome consists of DNA and all the genes in one set of chromosomes. Tijo and Levan (1956) cultured somatic cells from fibroblasts of human embryos and counted the human chromosome number as 46, or 23 chromosome sets. Out of these 22 pairs are autosomes and one pair is sex chromosome. In males the sex chromosomes are XY, whereas XX in females. The Y-chromosome contains genes that determine the normal development of testis. The X-chromosome carries the genes governing haemophilia, colour-blindness, muscular dystrophy and gonadal development.

Karyotype is the chromosomal complement of an organism. For karyotyping of human chromosomes, venous blood is taken for leucocytes, their cell division is arrested at metaphase stage by colchicines treatment. The chromosomes are arranged in an orderly fashion in homologus pairs and following informations are collected:1. Number of chromosomes per cell.2. Shape and size of the chromosome.3. Centromeric index, as a ratio of short arm length to long arm length. (C.I= Short arm/Long arm)4. Composition of the sex chromosomes.5. Identification of any chromosomal abnormalities.

From the study of human metaphase chromosomes, the 23 pairs are classified into seven groups, according to decreasing size, with one exception that chromosome 22 is longer than chromosome 21. Group A consists of the longest metacentric chromosomes and group G consists of the shortest acrocentric chromosomes. The X chromosome which belongs to group C is the third largest chromosome.

BANDING TECHNIQUES

A decisive step forward in human cytogenetics was the invention of banding technique that differentiate the chromosomes into transverse bands of different lengths. With these methods, all the

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Group Chromosomes TypeA 1 – 3 MetacentricB 4 – 5 SubmetacentricC 6 – 12 , X SubmetacentricD 13 – 15 AcrocentricE 16 – 18 SubmetacentricF 19 – 20 MetacentricG 21 – 22 , Y Acrocentric

chromosomes of man and many other organisms, and even the breakpoints in most structural rearrangements can be identified. The main banding techniques are:

1. Q-banding. When chromosomes are stained with quinacrine HCl or quinacrine mustard and studied with fluorescence microscope, they show bands of different brightness called Q-bands (quinacrine bands). Slides stained with quinacrine are not permanent, and after a couple of photomicrographic exposure the fluorescence fades too much to be usable.

2. G-banding. It involves staining with Giemsa. Giemsa banding yields essentially the same information as Q-banding, only the bright fluorescent Q-bands are now darkly stained whereas the Q-dark regions are light. The G-banded slides are permanent and are therefore more suitable for routine work.

3. R-banding. The banding pattern is the reverse of G-banding, i.e., the bands that are dark with R-banding are light with G-banding and vice versa. Although the banding reveals nothing new as compared to Q-banding or G-banding, but it is useful when chromosome ends are especially studied, as in distal deletion and translocation. A modification of R-banding, called T-banding brings out mainly the tips of chromosomes. It also utilizes the Giemsa stain but the chromosomes are first treated with acid and then with alkali. It brings out the heterochromatic regions around the centromere.

CHROMOSOME NUMBER

HEREDITARY DISEASES CHARACTERISTICS

1 Gaucher’s Disease Chronic enzyme deficiency2 Ehlers-Danios Syndrome Disease of connective tissue3 Retinitis Pigmentosa Progressive degeneration of the retina4 Huntington’s Disease Nerve degeneration5 Familial Adenomatous

Polyposis (FAP)Colon cancer

6 Spinocerebellar Ataxia Destruction of nerves of brain and spinal cord7 Cystic Fibrosis Mucus in lungs, breathing problem8 None None9 Melanoma Skin cancer

10 Multiple Endocrine Neoplasia Cancer of endocrine glands11 Sickle Cell Anaemia Anaemia in which RBCs become sickle

shaped12 Phenylketonuria Metabolism disorder, may result in mental

retardation13 Retinoblastoma Tumor of eye during childhood14 Alzheimer’s Disease Degenerative brain disorder15 Tay-Sachs Disease Lipid metabolism disorder16 Polycystic Kidney Disease Cysts in kidneys resulting in their enlargement17 Breast Cancer Tumors of breast18 Amyloidosis Accumulation of insoluble fibrillar protein in the

tissues19 Hypercholesterolemia High cholesterol level20 ADA Immune Deficiency Abnormal function of the immune system21 Amyotrophic Lateral

Sclerosis (ALS)Degenerative nerve disease, often lethal

22 Glucose-Galactose Malabsorption Syndrome

Fatal digestive disorder

X Haemophilia A and Muscular Dystrophy

Clotting deficiency, progressive degeneration of the muscles

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Fig. 14.8. Conversion of a normal proto-oncogene into an oncogene by various factors.

Y Azoospermia Absence of sperms in semen

Table 14.1. Hereditary diseases in humans with chromosome number and characteristics.

ONCOGENES AND CANCER

Cancer is a generic term for those cells which have lost the usual control over their growth and division. Such cells are called neoplastic cells. When normal cells divide, there are control mechanisms to regulate their growth and division. One such control is called as contact inhibition, i.e., normal cells in a culture stop growing when their plasma membranes come into contact with one another. However cancerous cells do not operate contact inhibition, these cells continue to divide and give rise to a tissue mass called tumor or neoplasm.

A neoplasm is a population of potentially cancerous cells growing out of control. There are two types of neoplasm both of which are expressions of abnormal growth namely benign and malignant.1. Benign tumors. Tumors that remain localized in a specific area at the site of origin, forming a single mass enclosed in a capsule, are called benign tumors. These are outgrowths that are self limiting, i.e., they grow to a certain size and then stop or regress. Usually they are not fatal. Benign tumors can be removed effectively with surgery. They usually do not reappear.

2. Malignant tumors. These tumors are cancerous, usually show unlimited growth; they escape the rules of differentiation and grow wild. They also have the ability to infiltrate and destroy normal tissues, and most malignant tumors are also capable of spreading to new sites by metastasis. When metastasizing cells gain access to blood vessels, the circulating blood carries those cells throughout the body. When they lodge at distant body site, the cells continue to grow, leading to tumor formation. These outgrowth their blood supply and the rapidly increasing number of cells compress the small blood vessels. This is called ischaemic necrosis. Cancer or malignant tumors are uncapsulated and invasive. Their cells may exhibit different degree of resemblance to the tissue cells from which these have originated. The partial loss of differentiation is termed as dysplasia and complete loss, so that the tumor no longer resembles the tissue of its origin is called anaplasia.

Characteristics of Cancer Cells. (a) These cells have abnormally large nuclei with abnormal chromosome number.(b) As compared to normal cells, these have large number of endoplasmic reticulum and ribosomes.

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(c) Aerobic respiration is depressed in tumor cells. Their normal glucose requirement is 20 times than that of a normal cell; and produce lactic acid under aerobic respiration. This places a burden on the liver, which must use ATP to get rid of lactate.(d) they have the capability of formation of local blood vessels called angiogenesis.

Types of Cancers. Cancer are broadly divided into four types according to the type of cells they affect.1. Carcinoma: It includes tumors of brain, breast, skin, etc. These are derived from the epithelial tissue, originating either from the ectoderm or endoderm. These are the most common types of cancers and are divided into squamous carcinoma (cancer of epithelial tissue) and adeno carcinoma (cancer of glands).2. Sarcoma: These are tumors of connective tissue, cartilage, bone and muscles which are mesodermal in origin. These are named according to the type of tissue in which they are found. e.g. Fibrosarcoma (cancer of fibrous connective tissue), liposarcoma (cancer of adipose tissue), chondrosarcoma (cancer of cartilage cells), osteosarcoma (cancer of bone), myosarcoma (cancer of muscles) which is of two types- leiomyosarcoma (cancer of smooth muscles) and rhabdomyosarcoma (cancer of striped muscles).3. Lymphoma: These are tumors of lymph nodes, bone marrow, liver and spleen, resulting in the production of large number of lymphocytes. e.g. Hodgkin’s disease, Mycosis fungoides.4. Leukaemia: These are tumors of white blood corpuscles (WBC) or leucocytes, leading to increase in the number of leucocytes. These are of various types- Melanomas (cancer of pigment cells), gilomas (cancer of glial cells of brain), glomangioma (cancer of blood vessels of the skin).

Tumor Markers. Many cancers are associated with the abnormal production of enzymes, proteins and hormones, which can be measured in plasma or serum; these are called tumor markers. They are useful in differentiating malignant and benign condition of a tumor, and also predict the effect of therapy in asymptomatic persons.

Markers CancersCarcino embryonic agent (CEA) Colon, lung, breast, pancreas

Human chorionic gonadotrophin (HCG) Trophoblast, germ cellsCalcitonis Thyroid

Prostatic acid phosphate (PAP) Prostrate

Table 14.2. Clinically used tumor markers.

Cancer is caused by mutation in the broadest sense of the word. There are convincing evidences that the overwhelming majority of malignant tumors have a clonal origin, a change that takes place in a single cell from which the entire tumor is derived. In primary tumors all cells may display the same abnormal chromosome constitution. It is obvious that malignant disease depends to a great extent on genetic factors. It is also known that most, possibly all, carcinogens are mutagens, however, not all mutagens necessarily induce cancer. A carcinogen is any agent (e.g., mutagenic chemicals, ionizing radiations, and certain viruses) that can promote a cancerous state.

Cancer is generally conceded to involve at least two major steps. The first step, termed initiation, results from a single exposure to a carcinogen. The second step, called promotion, involves one or more exposures to the same initiator or even to unrelated substances called promoters that complete the conversion of a normal cell to a neoplastic cell.. In general, the time interval between the exposure to an initiator and the promoter is not critical. However, the order of application is critical; the individual must be exposed to the initiator first, followed by the promoter. The promotion stage is a gradual process, often requiring many weeks in rodents and years in humans. Phorbol esters are among the most well known promoters. There are also substances that can act as initiator and promoter both. e.g. polycyclic hydrocarbons.

So-called proto-oncogenes are normal genes present in all metazoan cells. What roles they play under normal condition is mostly unknown. Viruses for long time been known to cause cancer in animals, the Rous sarcoma virus, a retrovirus (RNA virus) that induces malignant tumors in chickens, was

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discovered as early as 1911. Genes homologus to cellular proto-oncogenes are found in retroviruses known to cause cancer in various animal species. They transform cells either by being inserted into the host genome or by being present in multiple copies in the host cell. It is thought that the retroviruses picked up the oncogenes from the metazoan cells they had infected. A normal cell is transformed when one or more proto-oncogenes in it are activated, which can occur through mechanisms such as point mutation, position effect or amplification. Although certain constant chromosomal abnormalities are involved in the origin of cancer, most of the observed aberrations, both numerical and structural, arise during the progression of a malignant disease, and they in turn affect the further development of the tumors.

Therapy Principle InvolvedAnti-angiogenesis Angiostatin and other muscles.

Apoptosis promoters Develop agents that stimulate apoptosis in tumor cells.Cell cycle inhibitor Develop agents that inhibit key steps of cell cycle in tumor cells.

Gene therapy Replace tumor suppression protein or mutant repair enzyme.Metastasis inhibitors Inhibitors of proteases thereby inhibiting metastasis.

Monoclonal antibodies Directed against oncogene encoded receptors.

RibozymesDegrade mRNA molecules thereby inhibiting synthesis of

proteins and expression of tumor cells.

VaccinesInject peptides from tumor specific proteins to increase T-cell

immune response.

Table 14.3. Various types of cancer therapies and the principle involved in them.

USE OF HUMAN GENETICS IN MEDICAL SCIENCE

Genetic Counseling. It has now been widely used in medical practice, for couples who believe that there may be risk of producing a defective child. Such parents may either avoid from having any child or may undergo abortion after ascertaining about the defective foetus. Genetic counseling is helpful to those having a family history of a disease and the parents may like to know the chances of having the child free or affected of that disease. In a case, if a defect is found to be recessive and both the parents are normal, then the chances of having a defective child is one in four.

Antenatal Diagnosis. This method involves the use of amniocentesis. When a pregnant woman is suspected of bearing a child with genetic defect, it is desirable to diagnose the condition in the foetus. This can be done by taking out amniotic fluid and then screening the foetal cells for any genetic disorder. If a disease is detected, abortion of such foetus can be recommended. However, if abortion is not acceptable to parents, carrying of antenatal diagnosis is useless.

Making Choice of Baby’s Sex. By amniocentesis, it is possible to draw out the amniotic fluid containing foetal cells whose examination for the Barr bodies will confirm the sex of the developing foetus. There are also techniques available to separate Y-chromosome sperm from X-chromosome sperm, so that the couple may choose the sex of the child prior to fertilization. But this technique have been condemned by many sociologists in fear of disturbance of the sex ratio leading to various problems.

Gene Therapy. It is the treatment of disease by replacing, altering or supplementing a gene that is absent or abnormal and whose absence or abnormality is responsible for the disease. It is unique in that it employs the genetic material, DNA itself as the means of treatment. Large variety of genes are now

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Chorionic Villus Sampling (CVS) is a technique in which a small amount of foetal tissue is suctioned from placenta. These rapidly growing cells can be karyotyped immediately. The procedure can be performed at only 8 to 10 weeks of pregnancy i.e., even earlier than amniocentesis.

Fig. 14.9. Steps involved in human gene therapy.

being tested for use in gene therapy. e.g.: gene for the treatment of cystic fibrosis called as CFTR, genes for factors VIII and IX, deficiency of which causes haemophilia, genes called E1A and P53 that causes cancer cells to undergo cell death or revert to normal, AC6 genes which increases the ability of the heart to contract and may help in recovering heart failure, VEGF gene that induces growth of new blood vessels. Gene therapy can be used at two different levels: (a) Patient therapy, in which cell with healthy genes may be introduced in the affected tissue, so that the healthy gene overcomes the defect without affecting the inheritance of the patient. (b) Embryo therapy, in which the genetic constitution of embryo at the post-zygotic level is altered so that the inheritance is affected.

DNA Fingerprinting. This technique was discovered by Alec Jeffreys (1985). It is based on the fact that the DNA of each individual is interrupted by a series of identical DNA sequences called repetitive DNA or tandem repeats. The pattern, length and number of these repeats are unique for each individual. In this technique identity of a person with the help of blood stains, semen or hair root is possible with absolute certainty. DNA is isolated from any of the above specimens and subjected to southern blotting, where a pattern of bands is observed. This band is unique for every individual. An X-ray film is developed to make visible the pattern of bands which is known as DNA fingerprint. The forensic application of DNA fingerprinting technique involves a comparision between the DNA fingerprint obtained from the cell at a crime scene with a DNA fingerprint of the suspect.

The above technique will allow the identification of rapists in rape cases and of paternity disputes in case of doubtful parentage. In a child, one half of the band comes from the mother and the other half from the father. In case of a real father, all the parental bands in child’s DNA fingerprint must match with that of father’s DNA fingerprint. In India, DNA fingerprinting tests are carried out at Centre for Cell and Molecular Biology (CCMB), Hyderabad.

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COMPETITION DESK # 14

1. Genes A and B are necessary for normal hearing. A deaf man marries a deaf woman and all their children have normal fearing. The genotype of the parents are(a) AAbb and AAbb(b) Aabb and aaBb(c) AAbb and aaBB(d) aaBB and aaBb

2. An oriental man with brown eyes married a European female with blue eyes. What will be the colour of the eye of their children ?(a) one blue eyed, one brown eyed(b) all blue eyed(c) all brown eyed(d) three brown eyed, one blue eyed

3. Hypertrichosis is sex linked character associated with the(a) Y-chromosome (b) X-chromosome(c) XX chromosome(d) XY chromosome

4. An embryo resulting from the mating of two albino rabbits is transplanted into the uterus of a brown rabbit. The phenotype of this transplant will most probably be(a) brown (b) white(c) roan (d) none of these

5. Which one of the following is a correct pair ?(a) Polydactyly – codominance(b) Shull – heterosis(c) Straight hairs – dominant(d) Brown eye colour – recessive

6. Which condition is caused by mutations that involve entire chromosome rather than a single gene ?(a) Haemophilia(b) Phenylketonuria(c) Down’s syndrome(d) Sickle cell anaemia

7. The maximum number of Barr bodies in a cell from Down’s syndrome female is(a) 0 (b) 1(c) 2 (d) 3

8. A pregnant woman, who has done amniocentesis test, finds an extra Barr body in her embryo. The syndrome likely to be associated with the embryo is(a) Patau’s (b) Klinefelter’s(c) Down’s (d) Edward’s

9. In Down’s syndrome each cell has how many chromosomes ?(a) 21st pair having one less.(b) 23rd pair with one less.(c) 45 chromosomes.(d) 47 chromosomes.

10. 44 + X in a person shows the syndrome(a) Patau’s (b) Klinefelter’s(c) Turner’s (d) Edward’s

11. Webbed neck is a characteristic of(a) Patau’s (b) Klinefelter’s(c) Down’s (d) Turner’s

12. The genetic event in Turner’s syndrome (XO) is probably (a) non-disjunction (b) parental imprinting(c) monoploidy (d) segregation

13. Which of the following have equal number of chromosomes ?(a) Klinefelter’s syndrome and Down’s syndrome(b) Klinefelter’s syndrome and Turner’s syndrome(c) Turner’s syndrome and Down’s syndrome(d) Turner’s syndrome and gynandromorphs

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14. A holandric gene is known for hypertrichosis. When a man with hairy ears marries a normal woman, what percentage of their daughters would be expected to have hairy ears(a) 0% (b) 100%(c) 50% (d) 2.5%

15. Baldness is more common in men than in women. It could be explained on the basis that(a) it is due to male hormone and genes are not involved.(b) baldness genes are located on Y-chromosome.(c) genes of baldness are autosomal but influenced by androgens.(d) genes of baldness are located on X-chromosome only.

16. Father has blood group A and mother has B. Both are heterozygous. If they have identical twins, the percentage probability of both twins having blood group A is(a) 100% (b) 50%(c) 75% (d) 25%

17. How many Barr bodies will be expected in an extreme Klinefelter’s syndrome with XXXXY ?(a) 1 (b) 2(c) 4 (d) 3

18. The human disease inherited as a simple recessive trait is(a) Cancer(b) Diabetes(c) Alzheimer’s disease(d) Tay Sach’s disease

19. Father of human genetics is(a) Tijo (b) Mendel(c) Garrod (d) Hargobind Khorana

20. Which amino acid of beta chain of haemoglobin is changed when normal haemoglobin is changed to sickle cell anaemia haemoglobin.(a) Leucine (b) Methinine(c) Valine (d) Glutamic acid

21. The autosomes of man has been classified in

(a) 3 groups (b) 4 groups(c) 5 groups (d) 7 groups

22. Mother of a sickle cell anaemic child will always be(a) affected (b) normal(c) carrier (d) none of these

23. Metastasis (a) is the preneoplastic stage of cancer(b) transforms proto-oncogenes into oncogenes(c) is the invasion of cancerous cells to surrounding tissues(d) is a form of cancer that is induced by radiations only

24. Carcinoma refers to(a) malignant tumors of connective tissue.(b) malignant tumors of skin or mucus membrane.(c) malignant tumors of colon.(d) benign tumors of connective tissue.

25. Which of the following is not a cancer(a) sarcoma (b) carcinoma(c) leukemia (d) glaucoma

26. In cancerous tissues(a) glucose uptake remains normal.(b) glucose uptake increases.(c) glucose uptake decreases.(d) none.

27. Treatment of cancer by gamma rays is called(a) hormone therapy(b) chemotherapy(c) radiation therapy(d) all of these

28. Cancer of prostrate gland is caused due to the exposure to(a) hydrocarbons (b) cadmium oxide(c) methane gas (d) strontium compound

29. During hybridization the children are superior to parents; it is (CMC 2003)(a) heterozygosity (b) heterosis(c) homozygosity (d) interbreeding

30. Lyon hypothesis deals with (HPMT 2000)(a) centromere position

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(b) genetic compatibility(c) genetic incompatibility(d) number of Barr bodies

31. After the age of 40, the percentage of syndrome increased in the offspring of a lady, it is due to (HPMT 1999)(a) lady becomes weak(b) oocytes can show disjunction(c) ovaries become weak(d) placenta becomes weak

32. Mental retardation is not related with (AMU 2000)(a) trisomy 21(b) phenylalanine hydroxylase(c) myelinization of neurons(d) additional Y-chromosome

33. Philadelphia chromosome is found in the patient suffering from (AIIMS 2000)(a) insomia (b) hepatitis(c) albinism (d) myelocytic anaemia

34. Number of chromosomes in Down’s syndrome is (AFMC 2005)(a) 46 (b) 47 (c) 48 (d) 49

35. The person which does not involve any change in sex chromosome number of an organism (AFMC 2002)(a) Down’s syndrome (b) Turner’s syndrome (c) Super male (d) Super female

36. A man has 6 daughters. What is the probability of next child being a son?

(AFMC 2000)(a) 10% (b) 50% (c) 100% (d) 75%

37. Except for identical twins, individuals are never alike in (AFMC 2002)(a) asexually reproducing organisms (b) binary fission (c) parthenogenesis (d) sexually reproducing organisms

38. XXY condition is found in (AFMC 2002)(a) Down’s syndrome

(b) Superfemales(c) Klinefelter’s syndrome (d) Turner’s syndrome

39. Trisomy of which chromosome is involved in Down’s syndrome? (AMU 2003)(a) 8th (b) 13th (c) 21st (d) 23rd

40. Philadelphia chromosome is found in the patient suffering from (AIIMS 2002)(a) Albinism (b) Insomia (c) Hepatitis (d)Myelocytic leukemia

41. In which type of colour blindness, colours are perceived as grey (AIIMS 2002)(a) Monochromasia (b) Dichromasia (c) Chromoasia (d) All the above

42. Phenylketonuria is referred as (AIIMS 2000)(a) acquired disease (b) congenital disease (c) Infectious disease (d) All of these

43. In which of the following disease, an extra X chromosome is present (AFMC 2001)(a) Down’s syndrome (b) Turner’s syndrome (c) Klinefelter’s syndrome (d) Bleeder’s disease

44. Among the following, colour blindness is related with (AFMC 2003)(a) Eye muscles (b) Rods (c) Cones (d) All

45. Phenlyketonuria, an inherited disease is characterized by (BHU 2004)(a) Decreased occurrence of phenylalanine in blood and urine(b) Increased occurrence of phenylalanine in blood and urine(c) Elimination of homogentisic acid in urine(d) Elimination of sugar in urine

46. What is trisomy for 21st chromosome called (BHU 2001)

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(a) Klinefelter’s syndrome (b) Mongolism (c) Sickle cell anaemia (d) Turner’s syndrome

47. Among the following, mental retardation is not related with (AMU 2000)(a) Phenyalanine hydroxylase (b) Myelinization of neurons (c) Additional Y-chromosome (d) Trisomy 21, mongolism

48. What could be the genotype of Rh+ person (AMU 2001)(a) RR (b) Rr (c) rr (d) both a and b

49. One of the genes present exclusively on the X-chromosome in humans is concerned with (AIIMS 2003)(a) Pattern baldness (b) Colour blindness (c) Facial hairs in males(d) Night blindness

50. Albinism and Phenylketonuria are disorders due to (AIIMS 2000)(a) Recessive autosomal genes(b) Dominant autosomal genes(c) Recessive sex genes(d) Dominant sex genes

51. A man has enlarged breasts, sparse hairs on the body and sex complement as XXY. He suffers from (AIIMS 2000)(a) Down’s syndrome(b) Klinefelter’s syndrome(b) Edward’s syndrome(d) Turner’s syndrome

52. A hereditary disease is (CBSE 2000)(a) Leprosy (b) Cataract (c) Blindness (d) Phenylketonuria

53. A human male is heterozygous for autosomal genes A and B, and is also hemizygous for haemophilic gene h. What proportion of his sperms will be abh? (CBSE 2004)(a) 1/8 (b) 1/32(c) 1/16 (d) 1/4

54. Down’s syndrome is caused by an extra copy of chromosome number 21. What percentage of offspring produced by an affected mother and a normal father would be affected by this disorder ? (CBSE 2003)(a) 50% (b) 25%(c) 100% (d) 75%

55. Which of the following is a correct match (CBSE 2002)(a) Down’s syndrome – 21st chromosome(b) Sickle cell anaemia – X-chromosome(c) Haemophilia – Y-chromosome(d) Parkinson’s disease – X and Y-chromosome

56. Male XX and female XY sometime occur due to (CBSE 2001)(a) deletion(b) transfer of segments in X and Y chromosomes(c) aneuploidy(d) hormonal imbalance

57. A person with 45 chromosomes and also the Y chromosome is absent, is suffering from (BHU 2003)(a) Down’s syndrome(b)Klinefelter’s syndrome(c) Turner’s syndrome(d) none of these

58. Sickle cell anaemia is due to (CBSE 2001)(a) change of amino acid in alpha chain of haemoglobin.(b) change of amino acid in beta chain of haemoglobin.(c) change of amino acid in both alpha and beta chains of haemoglobin.(d) change of amino acid in either alpha or beta chains of haemoglobin.

59. In human beings, multiple genes are involved in the inheritance of (PPMT 1997)(a) skin colour (b) PKU(c) colourblindness (d) sickle cell anaemia

60. Which kind of evidence suggested that man is more closely related to chimpanzee than with other hominoid apes ? (CBSE 2004)

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(a) evidence from DNA from sex chromosomes only.(b) comparision of chromosomal morphology only.(c) evidence from fossil remains and the fossil mitochondrial DNA alone.(d) evidence from DNA extracted from sex chromosome, autosome and mitochondria.

61. Cancer cells are more easily damaged by radiation than normal cells because they are (CBSE 2004) (a) starved of mutation(b) undergoing rapid division(c) difference in structure(d) non-dividing

62. Which of the following is a sexually transmitted disease? (DPMT 2003)(a) hepatitis A (b) hepatitis B(c) hepatitis C (d) hepatitis D

63. Cancer caused in lungs, kidney and stomach is called (BVP Pune 2003)(a) sarcoma (b) carcinoma(c) lymphoma (d) glaucoma

64. Which of the following is a carcinogen ? (BVP Pune 2003)(a) H2S (b) Asbestos(c) Lead (d) Suspended particles

65. In cancer there is (WARDHA 2003)(a) hyperplaced epithelial tissues.(b) malignant growth of epithelial tissues.(c) suppressed growth of epithelial tissues.(d) all of these.

66. Proliferation of cancer cells is not limited because (KPMT 2003)(a) differing cholesterol level(b) differing surface proteins(c) deficiency of steroids(d) aberrant chromosome complement

67. Cancer of both the kidneys is called as (HPMT 2003)(a) Bloom syndrome(b) Wilm’s tumor(c) Adenocarcinoma(d) both b and c

68. Henson’s disease is another name for (AMU 2003)(a) leprosy (b) tuberculosis(c) typhoid (d) malaria

69. Vinyl chloride causes cancer of (AMU 2003)(a) stomach (b) lungs(c) prostrate (d) kidneys

70. For detection of cancer, the isotope used is (CBSE 2002)(a) Caesium60 (b) Iodine131

(c) Radium (d) Uranium238

71. Which one of the following cancer is prevalent in human beings ? (MPPMT 2002)(a) Lymphoma (b) Carcinoma(c) Sarcoma (d) Melanoma

72. Abnormal growth of the tumor in cancer is due to (BHU 2003)(a) abnormal mitotic division(b) accumulation of body fluid(c) abnormal meiotic division(d) metastasis

73. Which one of the following condition though harmful in itself, is also a potential saviour from all mosquito borne infectious disease ? (CBSE 2003)(a) Pernicious anaemia(b) Leukemia(c) Thalassemia(d) Sickle cell anaemia

74. Test tube baby means (CBSE 1996)(a) a baby grown in a test tube(b) fertilized and developed embryo in a test tube.(c) fertilization and development in the uterus.(d) fertilization in test tube and development in uterus.

75. G-6-P dehydrogenase deficiency is associated with haemolysis of (CBSE 2003)(a) Lymphocytes (b) RBCs (c) Platelets (d)Leucocytes

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76. Both sickle cell anaemia and Huntington’s chorea are (CBSE 2006)(a) virus related disease.(b) bacteria related disease.(c) congenital disorders.(d) Pollutant indico disorders

77. The causative agent of mad-cow disease is (CBSE 2006)(a) virus (b) bacteria(c) prion (D) worm

78. Sickle cell anaemia has not been eliminated from the African population because (CBSE 2006)(a) it is controlled by dominant genes.(b) it is controlled by recessive genes

(c) it is not a fatal disease.(d) it provides immunity against malaria.

79. Parents are colourblind. What is the phenotype of grandsons in F2 generation? (JIPMER 2002)(a) 50% normal, 50% colourblind(b) all normal(c) all colourblind(d) all are carriers

80. Down’s syndrome means (BVP Pune 2002)(a) an extra autosome chromosome(b) extra Y-chromosome(c) a loss of chromosome(d) extra X-chromosome

ANSWERS # 14

1. c 2. a 3. a 4. b 5. b 6. c 7. b 8. b 9. d 10. c11. d 12. a 13. a 14. a 15. c 16. d 17. d 18. d 19. c 20. d21. d 22. c 23. c 24. b 25. d 26. b 27. c 28. d 29. b 30. d31. b 32. c 33. d 34. b 35. a 36. b 37. d 38. c 39. c 40. d41. a 42. b 43. c 44. c 45. b 46. b 47. b 48. d 49. b 50. a51. b 52. d 53. a 54. a 55. a 56. d 57. c 58. b 59. a 60. d61. b 62. b 63. b 64. b 65. b 66. b 67. d 68. a 69. b 70. b71. b 72. a 73. d 74. d 75. b 76. c 77. c 78. b 79. c 80. a

EXPLANATION

4. (b): The coat colour in rabbits is governed by the genes of the parents. If the parents are albino, the offspring will also be albino; its phenotype will not be affected by the external environment, i.e. uterus of brown rabbit.

7. (b): Down’s syndrome is trisomy of 21st chromosome and Barr bodies are related with the sex chromosomes. There is no relation of Down’s syndrome with Barr bodies. The number will remain the same in normal person or a Down syndromic person.

8. (b): An extra Barr body means presence of two X-chromosomes, i.e. Klinefelter’s syndrome. The rest of the options are related to autosomal trisomies and therefore not concerned with the increase or decrease in the number of Barr bodies.

13. (a): In Klinefelter’s syndrome the total number of chromosomes is 47 (44 + XXY) and in Down’s syndrome also the total number of chromosomes is 47 (44 + 1 extra 21st chromosome + XX or XY).

14. (a): Holandric genes means the genes located on the Y-chromosome. The Y-chromosome is not found in females so the daughters will never inherit any disorder present on it.

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15. (c): Pattern baldness is a sex-influenced trait. A sex-influenced allele is dominant in one sex but recessive in the other. Hormonal differences can cause the difference in expression.

20. (d): Sickle cell anaemia occurs due to inheritance of a defective allele coding for β-globin. It results in the transformation of Hb-A into Hb-S in which glutamic acid is replaced by valine in each of the two β-chains of haemoglobin.

25. (d): Glaucoma is an eye disease.

26. (b): The normal glucose requirement of cancerous tissues is 20 times than that of a normal cell; and produce lactic acid under aerobic respiration.

48. (d): Rh positive is the presence of Rh factor in as person, either homozygous dominant (RR) or heterozygous dominant (Rr). rr genotype refers to a Rh negative person.

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