GENETIC DISORDERS

Sex chromosome
• Sex chromosome, either of a pair of
chromosomes that determine whether an
individual is male or female.
• The sex chromosomes of human beings and other
mammals are designated by scientists as X and Y.
• In humans the sex chromosomes consist of one
pair of the total of 23 pairs of chromosomes.
• The other 22 pairs of chromosomes are called 
autosomes.
• Individuals having two X chromosomes (XX) are female;
individuals having one X chromosome and one Y
chromosome (XY) are male.
• The X chromosome resembles a large autosomal
chromosome with a long and a short arm.
• The Y chromosome has one long arm and a very short
second arm.
• This path to maleness or femaleness originates at the
moment of meiosis, when a cell divides to produce 
gametes, or sex cells having half the normal number of
chromosomes. 
• During meiosis the male XY sex-chromosome pair
separates and passes on an X or a Y to separate
gametes; the result is that one-half of the gametes
(sperm) that are formed contains the X chromosome
and the other half contains the Y chromosome.
• The female has two X chromosomes, and all female
egg cells normally carry a single X. The eggs fertilized
by X-bearing sperm become females (XX), whereas
those fertilized by Y-bearing sperm become males
(XY).
• The effects of genes
carried only on the Y
chromosome are, of
course, expressed only in
males.
• Most of these genes are
the so-called maleness
determiners, which are
necessary for
development of the testes
 in the fetus.
 Genetic disorders
• An inherited medical condition caused by a
DNA abnormality.

• A genetic disorder is a disease that is caused

by a change, or mutation, in an individual's
DNA sequence. A genetic disorder is an illness
caused by changes in a person's DNA.
• Genetic disorders can be caused by
a mutation in one gene (monogenic disorder),
by mutations in multiple genes (multifactorial
inheritance disorder), by a combination of
gene mutations and environmental factors, or
by damage to chromosomes (changes in the
number or structure of entire chromosomes
 Mendelian Disorders:

• These are mainly determined by alteration or mutation in

the single gene.
• These disorders are transmitted in next generation according
to the principle of inheritance and can be studied by
pedigree analysis. These can be dominant or recessive.
• For example, Autosomal dominant disorder are
Osteogenesis imperfecta, polycystic kidney disease,
Huntington’s Disease, Fatal familial Insomnia, etc.
• Autosomal recessive disorder are Sickle cell anaemia, cystic
fibrosis, xeroderma pigmentosum, Albinism, Galactosemia
etc.
 Cystic Fibrosis
autosomal recessive inheritance pattern
•The cystic fibrosis transmembrane
conductance regulator (CFTR)
protein helps to maintain the balance of
salt and water on many surfaces in the
body, such as the surface of the lung. 

• SYMPTOMS
•Failure to thrive (inability to gain
weight despite having a good appetite
and taking in enough calories).
•Loose or oily stools.
•Trouble breathing.
•Recurrent wheezing.
•Frequent lung infections (recurrent 
pneumonia or bronchitis).
•Recurrent sinus infections.
•A nagging cough.
•Slow growth.
Hemophilia X-linked Recessive Disorder
 Haemophilia:

• It is a sex-linked recessive disease, which is transmitted from

an unaffected carrier female to some of the male offsprings.
Due to this, patient continues bleeding even on a minor injury
because of defective blood coagulation. The gene for
haemophilia is located on X-chromosome. The defective
alleles produce non-functional proteins, which later form a
non-functional cascade of proteins involved in blood clotting.
• The possibility of a female becoming a haemophilic is
extremely rare because mother of such a female has to be at-
least carrier and father should be haemophilic. For example,
females suffer from this disease only in homozygous
condition, i.e., XCXC. Queen Victoria was a carrier of
haemophilia and produced haemophilic individuals.
 Colour Blindness sex-linked recessive disorder
• It is a sex-linked recessive disorder, which results in defect
in either red or green cone of eye. It does not mean not
seeing any colour at all, in-fact it leads to the failure in
discrimination between red and green colour. The gene
for colour blindness is present on X-chromosome.
• It is more present in males (XCY) because of the presence
of only one X-chromosome as compared to two
chromosomes in females. A heterozygous female has
normal vision, but is a carrier and passes on the disorder
to some of her sons. Colour blindness like any other
inheritance show crisscross inheritance.
Sickle cell Anaemia autosomal recessive disorder 
 Sickle-Cell Anaemia
• It is a genetic disease of human beings.
• This disease is caused by a recessive gene Hbs.
• The normal gene HbA present on chromosome 11 has
undergone mutation to produce the recessive Hbs gene which
cause sickle-cell anaemia in homozygous condition (Hbs Hbs)
and the patient dies.
• In heterozygous condition (HbA Hbs) the patient survives, only
few R.B.Cs are affected.
• The R.B.Cs in this disease become sickle-shaped in venous
blood owing to the lower concentration of oxygen.
• This causes rupture of cells and severe haemolytic anaemia.
• Haemoglobin is a conjugate protein of heme and
globulin. It is formed of about 600 amino acids, two
identical a chains and two identical β chains.
• The sixth amino acid in chain of normal haemoglobin
is glutamic acid. In sickle-cell haemoglobin glutamic
acid is replaced by valine.
• The children homozygous for sickle-cell gene (HbsHbs)
produce rigid chains.
• When oxygen level of blood drops below certain
level, R.B.Cs undergo sickling.
• Such cells do not transport oxygen efficiently they
are removed by spleen causing severe anaemia.
• Individuals with HbAHbA genotype are normal,
those with HbsHbs genotype have sickle-cell
disease and those with HbAHBs geno-type have
the sickle-cell trait.
• Two individual with sickle-cell trait can produce
children with all three phenotypes. Individuals of
sickle-cell trait are immune to malaria.
Phenylketonuria (PKU)
 Phenylketonuria (PKU)  
autosomal recessive pattern

• This genetic disease was discovered by the Norwegian

physician A. Foiling in 1934.
• It is a single gene disorder caused by the mutation (=
change) of a gene on chromosome 12.
• PKU results when there is deficiency of liver enzyme
phenylalanine hydroxylase which converts
phenylalanine (an amino acid) into tyrosine (amino
acid).
• Thus, there is high level of phenyl alanine in the blood
and tissue fluid of the patient causing disease.
• Lack of enzyme phenyl alanine hydroxylase (an inborn
metabolic disorder) is due to the homozygous recessive
gene.
• Affected babies are normal at birth but within a few weeks
there is rise in plasma phenylalanine level which damages
the development of brain.
• Generally by six months severe mental retardation is
observed.
• If these affected children are not treated properly one third
of them are unable to walk and two-thirds cannot talk.
• Besides mental retardation other symptoms of
the disease include decreased pigmentation of
hair and skin and eczema.
• Large amount of phenylalanine and its
metabolites although excreted through urine
and sweat, their excess accumulation damages
the brain.
• The heterozygous individuals are normal but
carriers.
 Thalassemia:
autosome-linked recessive disease
 Thalassemia:

• It is an autosome-linked recessive disease,

which occurs due to either mutation or
deletion, resulting in reduced rate of synthesis
of one of the globin chains of haemoglobin.
• Anaemia is the main feature of this disease.
• Thalassemia is a genetic disorder in which
there is decreased production of one of the
globin chains found in hemoglobin.
• This oxygen-transporting molecule in blood
normally contains four globin chains, two
alpha (a) and two non-a, each with its own
heme group (made of an iron atom bound in
protoporphyrin ring).
• Thalassemia classification
• (i) Alpha (α) Thalassemia:
• It is controlled by the closely linked genes
HBA1 and HBA2 on chromosome. In this, the
production of globin gene is affected due to
the mutation or deletion of one or more
alleles.
• (ii) Beta (β) Thalassemia:
• It is controlled by a single gene HBB on
chromosome. It occurs due to the mutation in
one or both the alleles of the gene. Hence,
there is a reduced synthesis of beta globin of
haemoglobin.
• In sickle cell disease, an abnormal hemoglobin
protein (i.e., hemoglobin S) is made, but it
doesn't function correctly; however, in beta
thalassemia, the mutation in HBB results in
less hemoglobin protein being made. There
are actually several types of alpha and beta
thalassemia, each with varying severity of
symptoms