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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.

Fig. 14.1. Symbols used in making pedigree charts.

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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.

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

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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 Fig. 14.4. Amniocentesis technique showing procedure
in each of the two β-chains of used in detecting the amniotic fluid.
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 4th 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 15th 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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Cystic fibrosis. It is caused by the mutation in the 7th 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)

Fig. 14.5. Mongol.

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

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

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anopthalmia (absence of eyes) 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. Group Chromosomes Type
2. Shape and size of the chromosome. A 1–3 Metacentric
3. Centromeric index, as a ratio of short arm B 4–5 Submetacentric
length to long arm length. (C.I= Short arm/Long C 6 – 12 , X Submetacentric
arm) D 13 – 15 Acrocentric
4. Composition of the sex chromosomes. E 16 – 18 Submetacentric
5. Identification of any chromosomal F 19 – 20 Metacentric
abnormalities. G 21 – 22 , Y Acrocentric
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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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 HEREDITARY DISEASES CHARACTERISTICS

NUMBE
R
1 Gaucher’s Disease Chronic enzyme deficiency
2 Ehlers-Danios Syndrome Disease of connective tissue
3 Retinitis Pigmentosa Progressive degeneration of the retina
4 Huntington’s Disease Nerve degeneration
5 Familial Adenomatous Colon cancer
Polyposis (FAP)
6 Spinocerebellar Ataxia Destruction of nerves of brain and spinal cord
7 Cystic Fibrosis Mucus in lungs, breathing problem
8 None None
9 Melanoma Skin cancer
10 Multiple Endocrine Neoplasia Cancer of endocrine glands
11 Sickle Cell Anaemia Anaemia in which RBCs become sickle
shaped
12 Phenylketonuria Metabolism disorder, may result in mental
retardation
13 Retinoblastoma Tumor of eye during childhood
14 Alzheimer’s Disease Degenerative brain disorder
15 Tay-Sachs Disease Lipid metabolism disorder
16 Polycystic Kidney Disease Cysts in kidneys resulting in their enlargement
17 Breast Cancer Tumors of breast
18 Amyloidosis Accumulation of insoluble fibrillar protein in the
tissues
19 Hypercholesterolemia High cholesterol level
20 ADA Immune Deficiency Abnormal function of the immune system
21 Amyotrophic Lateral Degenerative nerve disease, often lethal
Sclerosis (ALS)
22 Glucose-Galactose Fatal digestive disorder
Malabsorption Syndrome
X Haemophilia A and Muscular Clotting deficiency, progressive degeneration
Dystrophy of the muscles
Y Azoospermia Absence of sperms in semen
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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.

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

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 Cancers
Carcino embryonic agent (CEA) Colon, lung, breast, pancreas
Human chorionic gonadotrophin (HCG) Trophoblast, germ cells
Calcitonis 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
discovered as early as 1911. Genes homologus to cellular proto-oncogenes are found in retroviruses
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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 Involved

Anti-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.
Degrade mRNA molecules thereby inhibiting synthesis of
Ribozymes
proteins and expression of tumor cells.
Inject peptides from tumor specific proteins to increase T-cell
Vaccines
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 Chorionic Villus Sampling (CVS) is
done by taking out amniotic fluid and then screening the a technique in which a small amount of
foetal cells for any genetic disorder. If a disease is detected, foetal tissue is suctioned from
abortion of such foetus can be recommended. However, if placenta. These rapidly growing cells
abortion is not acceptable to parents, carrying of antenatal can be karyotyped immediately. The
diagnosis is useless. procedure can be performed at only 8
to 10 weeks of pregnancy i.e., even
Making Choice of Baby’s Sex. By amniocentesis, it is earlier than amniocentesis.
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
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
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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.

Fig. 14.9. Steps involved in human gene therapy.

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 (a) 0 (b) 1
hearing. A deaf man marries a deaf woman (c) 2 (d) 3
and all their children have normal fearing.
The genotype of the parents are 8. A pregnant woman, who has done
(a) AAbb and AAbb amniocentesis test, finds an extra Barr body
(b) Aabb and aaBb in her embryo. The syndrome likely to be
(c) AAbb and aaBB associated with the embryo is
(d) aaBB and aaBb (a) Patau’s (b) Klinefelter’s
(c) Down’s (d) Edward’s
2. An oriental man with brown eyes married a
European female with blue eyes. What will 9. In Down’s syndrome each cell has how
be the colour of the eye of their children ? many chromosomes ?
(a) one blue eyed, one brown eyed (a) 21st pair having one less.
(b) all blue eyed (b) 23rd pair with one less.
(c) all brown eyed (c) 45 chromosomes.
(d) three brown eyed, one blue eyed (d) 47 chromosomes.

3. Hypertrichosis is sex linked character 10. 44 + X in a person shows the syndrome

associated with the (a) Patau’s (b) Klinefelter’s
(a) Y-chromosome (b) X-chromosome (c) Turner’s (d) Edward’s
(c) XX chromosome(d) XY chromosome
11. Webbed neck is a characteristic of
4. An embryo resulting from the mating of two (a) Patau’s (b) Klinefelter’s
albino rabbits is transplanted into the uterus (c) Down’s (d) Turner’s
of a brown rabbit. The phenotype of this
transplant will most probably be 12. The genetic event in Turner’s syndrome
(a) brown (b) white (XO) is probably
(c) roan (d) none of these (a) non-disjunction (b) parental imprinting
(c) monoploidy (d) segregation
5. Which one of the following is a correct
pair ? 13. Which of the following have equal number
(a) Polydactyly – codominance of chromosomes ?
(b) Shull – heterosis (a) Klinefelter’s syndrome and Down’s
(c) Straight hairs – dominant syndrome
(d) Brown eye colour – recessive (b) Klinefelter’s syndrome and Turner’s
syndrome
6. Which condition is caused by mutations that (c) Turner’s syndrome and Down’s
involve entire chromosome rather than a syndrome
single gene ? (d) Turner’s syndrome and gynandromorphs
(a) Haemophilia
(b) Phenylketonuria 14. A holandric gene is known for
(c) Down’s syndrome hypertrichosis. When a man with hairy ears
(d) Sickle cell anaemia marries a normal woman, what percentage
of their daughters would be expected to have
7. The maximum number of Barr bodies in a hairy ears
cell from Down’s syndrome female is (a) 0% (b) 100%
 13

(c) 50% (d) 2.5% (c) carrier (d) none of these

15. Baldness is more common in men than in 23. Metastasis

women. It could be explained on the basis (a) is the preneoplastic stage of cancer
that (b) transforms proto-oncogenes into
(a) it is due to male hormone and genes are oncogenes
not involved. (c) is the invasion of cancerous cells to
(b) baldness genes are located on Y- surrounding tissues
chromosome. (d) is a form of cancer that is induced by
(c) genes of baldness are autosomal but radiations only
influenced by androgens.
(d) genes of baldness are located on X- 24. Carcinoma refers to
chromosome only. (a) malignant tumors of connective tissue.
(b) malignant tumors of skin or mucus
16. Father has blood group A and mother has B. membrane.
Both are heterozygous. If they have identical (c) malignant tumors of colon.
twins, the percentage probability of both (d) benign tumors of connective tissue.
twins having blood group A is
(a) 100% (b) 50% 25. Which of the following is not a cancer
(c) 75% (d) 25% (a) sarcoma (b) carcinoma
(c) leukemia (d) glaucoma
17. How many Barr bodies will be expected in
an extreme Klinefelter’s syndrome with 26. In cancerous tissues
XXXXY ? (a) glucose uptake remains normal.
(a) 1 (b) 2 (b) glucose uptake increases.
(c) 4 (d) 3 (c) glucose uptake decreases.
(d) none.
18. The human disease inherited as a simple
recessive trait is 27. Treatment of cancer by gamma rays is called
(a) Cancer (a) hormone therapy
(b) Diabetes (b) chemotherapy
(c) Alzheimer’s disease (c) radiation therapy
(d) Tay Sach’s disease (d) all of these

19. Father of human genetics is 28. Cancer of prostrate gland is caused due to
(a) Tijo (b) Mendel the exposure to
(c) Garrod (d) Hargobind Khorana (a) hydrocarbons (b) cadmium oxide
(c) methane gas (d) strontium compound
20. Which amino acid of beta chain of
haemoglobin is changed when normal 29. During hybridization the children are
haemoglobin is changed to sickle cell superior to parents; it is (CMC 2003)
anaemia haemoglobin. (a) heterozygosity (b) heterosis
(a) Leucine (b) Methinine (c) homozygosity (d) interbreeding
(c) Valine (d) Glutamic acid
30. Lyon hypothesis deals with (HPMT 2000)
21. The autosomes of man has been classified in (a) centromere position
(a) 3 groups (b) 4 groups (b) genetic compatibility
(c) 5 groups (d) 7 groups (c) genetic incompatibility
(d) number of Barr bodies
22. Mother of a sickle cell anaemic child will
always be
(a) affected (b) normal
 14

31. After the age of 40, the percentage of 39. Trisomy of which chromosome is involved
syndrome increased in the offspring of a in Down’s syndrome? (AMU 2003)
lady, it is due to (HPMT 1999) (a) 8th (b) 13th
st
(a) lady becomes weak (c) 21 (d) 23rd
(b) oocytes can show disjunction
(c) ovaries become weak 40. Philadelphia chromosome is found in the
(d) placenta becomes weak patient suffering from (AIIMS 2002)
(a) Albinism (b) Insomia
32. Mental retardation is not related with (c) Hepatitis (d)Myelocytic leukemia
(AMU 2000)
(a) trisomy 21 41. In which type of colour blindness, colours
(b) phenylalanine hydroxylase are perceived as grey (AIIMS 2002)
(c) myelinization of neurons (a) Monochromasia
(d) additional Y-chromosome (b) Dichromasia
(c) Chromoasia
33. Philadelphia chromosome is found in the (d) All the above
patient suffering from (AIIMS 2000)
(a) insomia (b) hepatitis 42. Phenylketonuria is referred as (AIIMS
(c) albinism (d) myelocytic anaemia 2000)
(a) acquired disease
34. Number of chromosomes in Down’s (b) congenital disease
syndrome is (AFMC 2005) (c) Infectious disease
(a) 46 (b) 47 (d) All of these
(c) 48 (d) 49
43. In which of the following disease, an extra
35. The person which does not involve any X chromosome is present (AFMC 2001)
change in sex chromosome number of an (a) Down’s syndrome
organism (AFMC 2002) (b) Turner’s syndrome
(a) Down’s syndrome (c) Klinefelter’s syndrome
(b) Turner’s syndrome (d) Bleeder’s disease
(c) Super male
(d) Super female 44. Among the following, colour blindness is
related with (AFMC 2003)
36. A man has 6 daughters. What is the (a) Eye muscles (b) Rods
probability of next child being a son? (c) Cones (d) All
(AFMC 2000)
(a) 10% (b) 50% 45. Phenlyketonuria, an inherited disease is
(c) 100% (d) 75% characterized by (BHU 2004)
(a) Decreased occurrence of phenylalanine
37. Except for identical twins, individuals are in blood and urine
never alike in (AFMC 2002) (b) Increased occurrence of phenylalanine in
(a) asexually reproducing organisms blood and urine
(b) binary fission (c) Elimination of homogentisic acid in
(c) parthenogenesis urine
(d) sexually reproducing organisms (d) Elimination of sugar in urine

38. XXY condition is found in (AFMC 2002) 46. What is trisomy for 21st chromosome called
(a) Down’s syndrome (BHU 2001)
(b) Superfemales (a) Klinefelter’s syndrome
(c) Klinefelter’s syndrome (b) Mongolism
(d) Turner’s syndrome (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
15
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)
(a) evidence from DNA from sex
chromosomes only.
 16

(b) comparision of chromosomal (a) leprosy (b) tuberculosis

morphology only. (c) typhoid (d) malaria
(c) evidence from fossil remains and the
fossil mitochondrial DNA alone. 69. Vinyl chloride causes cancer of (AMU
(d) evidence from DNA extracted from sex 2003)
chromosome, autosome and mitochondria. (a) stomach (b) lungs
(c) prostrate (d) kidneys
61. Cancer cells are more easily damaged by
radiation than normal cells because they are 70. For detection of cancer, the isotope used is
(CBSE 2004) (CBSE 2002)
(a) starved of mutation (a) Caesium60 (b) Iodine131
(b) undergoing rapid division (c) Radium (d) Uranium238
(c) difference in structure
(d) non-dividing 71. Which one of the following cancer is
prevalent in human beings ? (MPPMT
62. Which of the following is a sexually 2002)
transmitted disease? (DPMT 2003) (a) Lymphoma (b) Carcinoma
(a) hepatitis A (b) hepatitis B (c) Sarcoma (d) Melanoma
(c) hepatitis C (d) hepatitis D
72. Abnormal growth of the tumor in cancer is
63. Cancer caused in lungs, kidney and stomach due to (BHU 2003)
is called (BVP Pune 2003) (a) abnormal mitotic division
(a) sarcoma (b) carcinoma (b) accumulation of body fluid
(c) lymphoma (d) glaucoma (c) abnormal meiotic division
(d) metastasis
64. Which of the following is a carcinogen ?
(BVP Pune 2003) 73. Which one of the following condition
(a) H2S (b) Asbestos though harmful in itself, is also a potential
(c) Lead (d) Suspended particles saviour from all mosquito borne infectious
disease ? (CBSE 2003)
65. In cancer there is (WARDHA 2003) (a) Pernicious anaemia
(a) hyperplaced epithelial tissues. (b) Leukemia
(b) malignant growth of epithelial tissues. (c) Thalassemia
(c) suppressed growth of epithelial tissues. (d) Sickle cell anaemia
(d) all of these.
74. Test tube baby means (CBSE 1996)
66. Proliferation of cancer cells is not limited (a) a baby grown in a test tube
because (KPMT 2003) (b) fertilized and developed embryo in a test
(a) differing cholesterol level tube.
(b) differing surface proteins (c) fertilization and development in the
(c) deficiency of steroids uterus.
(d) aberrant chromosome complement (d) fertilization in test tube and development
in uterus.
67. Cancer of both the kidneys is called as
(HPMT 2003) 75. G-6-P dehydrogenase deficiency is
(a) Bloom syndrome associated with haemolysis of (CBSE 2003)
(b) Wilm’s tumor (a) Lymphocytes (b) RBCs
(c) Adenocarcinoma (c) Platelets (d)Leucocytes
(d) both b and c

68. Henson’s disease is another name for 76. Both sickle cell anaemia and Huntington’s
(AMU 2003) chorea are (CBSE 2006)
 17

(a) virus related disease. (d) it provides immunity against malaria.

(b) bacteria related disease.
(c) congenital disorders. 79. Parents are colourblind. What is the
(d) Pollutant indico disorders phenotype of grandsons in F2 generation?
(JIPMER 2002)
77. The causative agent of mad-cow disease is (a) 50% normal, 50% colourblind
(CBSE 2006) (b) all normal
(a) virus (b) bacteria (c) all colourblind
(c) prion (D) worm (d) all are carriers

78. Sickle cell anaemia has not been eliminated 80. Down’s syndrome means (BVP Pune 2002)
from the African population because (CBSE (a) an extra autosome chromosome
2006) (b) extra Y-chromosome
(a) it is controlled by dominant genes. (c) a loss of chromosome
(b) it is controlled by recessive genes (d) extra X-chromosome
(c) it is not a fatal disease.

ANSWERS # 14

1. c 2. a 3. a 4. b 5. b 6. c 7. b 8. b 9. d 10. c
11. d 12. a 13. a 14. a 15. c 16. d 17. d 18. d 19. c 20. d
21. d 22. c 23. c 24. b 25. d 26. b 27. c 28. d 29. b 30. d
31. b 32. c 33. d 34. b 35. a 36. b 37. d 38. c 39. c 40. d
41. a 42. b 43. c 44. c 45. b 46. b 47. b 48. d 49. b 50. a
51. b 52. d 53. a 54. a 55. a 56. d 57. c 58. b 59. a 60. d
61. b 62. b 63. b 64. b 65. b 66. b 67. d 68. a 69. b 70. b
71. 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.
 18

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.