MODULE 1

GENETICS, MUTATIONS
AND GENETIC DISORDERS
Presentation by,
Dr. Teena Rajan
Test Cross
• The purpose of the test cross is to determine the genetic makeup of
the dominant organism.
• Mendel wanted to do this so that he could be sure he was working
with a dominant organism which was homozygous, or contained only
dominant alleles.
• However, the phenotype alone doesn’t not tell you the genotype of
an organism. The organism could be hiding a recessive, non-
expressed allele.
• To find out what this unknown allele was, Mendel developed the
technique of breeding this individual with a homozygous
recessive individual for the same trait.
Back cross
• Back crossing is the method of mating a hybrid with one of its parents
or a genetically identical individual in an attempt to develop infants with
a genetic identity identical to that of the parent
 Incomplete dominance
• Incomplete dominance is when a
dominant allele, or form of a gene,
does not completely mask the effects
of a recessive allele, and the organism ’s
resulting physical appearance shows a
blending of both alleles.
• It is also called semi-dominance or
partial dominance.
• One example is shown in Mirabilis
jalapa (4 O’ clock plant).
Sex-linked characters
• The physical/phenotypic traits that are determined by the genes
present on the sex chromosomes (allosomes), i.e., the X and Y
chromosomes are known as sex-linked characteristics or sex-linked
traits.
X-linked inheritance
• X-linked inheritance means that the gene causing the trait or the
disorder is located on the X chromosome.
• Females have two X chromosomes; males have one X and one Y.
• Genes on the X chromosome can be recessive or dominant. Their
expression in females and males is not the same.
X Linked Recessive Inheritance
• X-linked recessive genes are expressed in females only if there are
two copies of the gene (one on each X chromosome).
• However, for males, there needs to be only one copy of an X-linked
recessive gene in order for the trait or disorder to be expressed.

• For example, a woman can carry a recessive gene on one of the X

chromosomes unknowingly, and pass it on to a son, who will express
the trait.
X-linked Dominant Inheritance
• A single X-chromosome can cause the mutation in both males and
females in X-linked dominant inheritance.
• The affected male passes its gene to all of their daughters, but not to
their sons.
Y – linked Inheritance (Holandric inheritance)
• It is transferred from father to son
only and can affect every generation.
• The most common examples of this
type of inheritance include failures
in the SRY gene (sex determining
region of the Y )
• the SRY gene provides instructions
for making a protein called the sex-
determining region Y protein.
• Mutations and changes in this gene
can cause disorders in the male
child.
Sex linked inheritance in human beings
• Colour blindness
• Haemophilia
Colour blindness
• It is caused by mutations in genes located on the X chromosome.
• There are several different types of red-green color blindness, but the most common form
is caused by mutations in the genes, which encode photopigments that are responsible
for detecting red and green colors in the eye.
• Red-green color blindness is inherited in an X-linked recessive manner, meaning that
females who carry the mutated gene on one of their X chromosomes typically do not show
symptoms because they have another normal X chromosome that can compensate for the
mutated gene.
• However, males who inherit the mutated gene on their one X chromosome will develop
red-green color blindness because they do not have a second normal X chromosome to
compensate for the mutation
Haemophilia
• Hemophilia is a genetic disorder that affects the blood's ability to clot normally, resulting
in prolonged bleeding and increased risk of hemorrhage.
• Hemophilia is caused by mutations in genes that provide instructions for making proteins
necessary for blood clotting, most commonly the F8 gene (which produces clotting
factor VIII) and the F9 gene (which produces clotting factor IX –Christmas
factor).
• Hemophilia A is caused by a deficiency of clotting factor VIII, while Hemophilia B is
caused by a deficiency of clotting factor IX.
• Hemophilia is inherited in an X-linked recessive manner, meaning the mutated gene is
located on the X chromosome.
• Because males have only one X chromosome, they are more likely to be affected by
hemophilia than females.
• In females, mutation of both the genes is required to cause the disorder. If only one copy
of the gene is mutated, they remain as carriers of the disease.
• Treatment for hemophilia typically involves regular infusions of clotting factor
concentrates.
Sex limited traits
• Characters that can just be expressed in single sex.
• Genes on both the autosomal or sex chromosomes can produce
them.
• Sex-limited genes are activated only by some hormones.
• These genes causes the two sexes to exhibit different traits or
phenotypes despite having the same genotype.
• Eg.
• Gene for milk secretion is present in males and females, but milk is secreted
only in females.
• Regulation of secondary sexual characters in human beings.
Sex-influenced traits
• Traits that are influenced or conditioned upon whether they occur in
a male or female body are known as sex-influenced or sex-
conditioned traits.
• These are Autosomal traits whose genes are not carried on the sex
chromosomes and are influenced by the sex of the individual.
• The traits are not due to specific genes but are by-products of sex
hormones.
• Eg :
• Beard in males.
• Baldness in males.
Genetic disorders.
• Disorders caused by one or more defects in the genome.
• Its of 2 types
• Mendelian disorders.
• Chromosomal disorders.
Mendelian disorders
• Genetic disorders that follow Mendel’s law of inheritance and are
caused due to mutation in a single gene and can be seen since birth.
• It may or may not be inherited.
• Inheritable genetic disorders are seen in germline cells.
• Non inheritable genetic disorders are triggered by mutations
• Mendelian disorders are of 2 types
Sex linked disorders
Autosomal mendelian disorders.
Autosomal dominant disorders
• Autosomal dominant disorders are a type of Mendelian disorder in
which a mutation in one copy of a gene on an autosome (a non-sex
chromosome) is enough to cause the disorder.
• In other words, an individual only needs to inherit one mutated copy
of the gene from one parent to develop the disorder.
Brachydactyly
• The main symptom of brachydactyly is
shortening of the bones in the fingers and/or
toes.
• Results from bone dystosis (disorder of
development of bone).
• Develops during blastogenesis (first 8 weeks of
embryonic life).
• It can cause syndactyly - a condition in which
fingers or toes are fused together, and
polydactyly - a condition in which there are extra
fingers or toes present.
AUTOSOMAL RECESSIVE
DISORDERS
• Autosomal recessive disorders are a type of Mendelian disorder in which
an individual must inherit two copies of a mutated gene (one from each
parent) to develop the disorder.

• If an individual inherits only one copy of the mutated gene, they are a
carrier of the disorder but typically do not show symptoms.
Phenylketonuria (PKU)
• It is an autosomal recessive disorder that affects the body's ability to break
down an amino acid called phenylalanine. This amino acid is found in
many foods, including milk, eggs, and meat.
• In individuals with PKU, the buildup of phenylalanine can cause
intellectual disability, seizures, behavioral problems, and other
complications.
• PKU is caused by a mutation in the gene that produces an enzyme called
phenylalanine hydroxylase (PAH), which is responsible for breaking
down phenylalanine in the body to tyrosine.
• Without this enzyme, phenylalanine accumulates in the blood and brain,
leading to the symptoms of PKU.
Galactosemia
• Autosomal recessive disorder in which both the parents must possess
a copy of the mutated gene.
• Galactosemia is caused by mutations in the GALT gene (galactose-1-
phosphate uridylyltransferase).
• GALT is responsible for breakdown of galactose into glucose.
• Galactose is a sugar byproduct of lactose found in breastmilk
Alkaptonuria
• Autosomal recessive disorder in which both the parents must possess
a copy of the mutated gene.
• Inherited due to mutation in HGD (Homogentisate 1,2- dioxygenase)
gene. This gene produces the enzyme for break down of aminoacids
phenylalanine and tyrosine.
• As a result, homogentisic acid (HGA) accumulates in the body,
leading to the characteristic symptoms of the condition.
• HGA is excreted from the body in urine, where it can oxidize and
turn brown when exposed to air.
• Over time, HGA can also accumulate in connective tissues
throughout the body, leading to a range of additional symptoms,
including joint pain and stiffness, skin pigmentation, kidney stones,
and heart valve problems.
Albinism
• It is a group of genetic disorders that affect the production of
melanin, the pigment that gives color to the skin, hair, and eyes.
• Results in characteristic features such as pale skin, white or light-
colored hair, and light-colored irises.
• It is caused by defect in the gene that produces MELANIN
• Autosomal recessive disorder in which both the parents must possess
a copy of the mutated gene.
• Types- Ocular albinism and oculocutaneous albinism.
• Oculocutaneous albinism affects the production of melanin in the
skin, hair, and eyes, while ocular albinism primarily affects the eyes
Sickle cell anemia
• Autosomal recessive lethal disorder
• It is a genetic disorder caused by a mutation in the HBB gene (at 6th codon of beta globin
chain from GAG to GUG). Hence, Amino acid GLUTAMATE (Glu) gets substituted by
VALINE (Val) at the 6th position.
• Beta-globin is a component of hemoglobin, a protein found in red blood cells that carries
oxygen throughout the body.
• In sickle cell anemia, the mutation causes the beta-globin protein to form abnormal,
crescent-shaped hemoglobin molecules, instead of the normal, round shape.
• These abnormal hemoglobin molecules can cause red blood cells to become stiff and
sticky, leading to the characteristic sickle shape.
• These sickle-shaped cells can get stuck in small blood vessels, reducing blood flow and
oxygen supply to various parts of the body, which can lead to pain, organ damage, and
increased risk of infections.
• The possible genotypes are
• HbA HbA , Homozygous dominant – This individual has two copies of
the normal HBB gene and does not have sickle cell anemia
• HbA HbS , Heterozygous (AS): This individual has one copy of the
normal HBB gene and one copy of the mutated HBB gene. They are a
carrier of sickle cell anemia, but typically do not have symptoms.
• HbS HbS , Homozygous recessive – This individual has two copies of
the mutated HBB gene and has sickle cell anemia.
SEX-LINKED MENDELIAN
DISORDERS
• Sex-linked Mendelian disorders are genetic disorders caused by mutations in genes located on the
sex chromosomes (X and Y chromosomes).
• Since females have two X chromosomes and males have one X and one Y chromosome, these
disorders can affect males and females differently
• In X-linked disorders, the gene responsible for the disorder is located on the X chromosome.
• Because males have only one X chromosome, they are more likely to be affected by X-linked
disorders than females.
• Females can be carriers of the disorder if they have one mutated X chromosome, but are typically
not affected unless they have two mutated X chromosomes.
• In Y-linked disorders, the gene responsible for the disorder is located on the Y chromosome.
• Since females do not have a Y chromosome, Y-linked disorders only affect males and are inherited
exclusively from their fathers
• Some examples of sex-linked Mendelian disorders include hemophilia, red-green color blindness
Chromosomal disorders
Results from a change in the number or structure of chromosomes.
Eg.
Down’s syndrome
Klinefelter’s syndrome
Turner’s syndrome
Chromosomal disorders
Down’s syndrome
• Down syndrome is a genetic disorder caused when abnormal cell
division results in an extra full or partial copy of chromosome 21.
Edward’s syndrome.
• Edwards syndrome, also known as trisomy 18, is a genetic disorder caused
by the presence of an extra copy of chromosome 18.
• Intellectual Disabilities: Individuals with Edwards syndrome often have
severe intellectual disabilities, which can impact their overall cognitive
development.
• Growth Retardation: Babies with trisomy 18 usually have growth delays,
both before and after birth. They may be smaller in size and weight than
typical newborns.
• Craniofacial Abnormalities:
• Small, abnormally shaped head (microcephaly).
• Prominent back of the head
• Small jaw (micrognathia).
• Low-set ears.
• Heart Defects: Many babies with Edwards syndrome have congenital heart
defects, which can contribute to the severity of the condition and impact
overall health.
Cri du chat syndrome
• Cri du chat syndrome, also known as 5p- (5p minus) syndrome, is a
rare genetic disorder caused by a deletion of genetic material on the
short arm of chromosome 5. The name "Cri du chat" is French for "cry
of the cat," referring to the distinctive cat-like cry that affected infants
often produce.
Symptoms
• Cat-Like Cry: Infants with Cri du chat syndrome often have a high-pitched cry that sounds similar to the cry
of a cat. This cry is typically present in the first months of life but may diminish as the child grows older.
• Intellectual Disabilities: Individuals with Cri du chat syndrome typically experience developmental delays
and intellectual disabilities. The extent of intellectual impairment varies, but most individuals have some
degree of cognitive impairment.
• Facial Features:
• Microcephaly (small head size).
• Round face.
• Hypertelorism (wide-set eyes).
• Downward slanting of the eyes.
• Small jaw (micrognathia).
• Growth Delays: Children with Cri du chat syndrome may have growth and motor skill delays. They may be
smaller in stature compared to their peers.
• Speech and Language Delays: Communication difficulties are common in individuals with Cri du chat
syndrome. Speech and language development may be delayed.
• Behavioral Issues: Some individuals may exhibit behavioral problems, including hyperactivity, aggression,
and repetitive movements.
Sex chromosomal Anomalies
Klinefelter’s syndrome
• A genetic condition that
results when a boy is born
with an extra copy of the X
chromosome.
• affect testicular growth,
resulting in smaller than
normal testicles, which can
lead to lower production of
testosterone.
Signs and symptoms
• Taller than average stature
• Longer legs, shorter torso and broader hips compared with other boys
• Absent, delayed or incomplete puberty
• After puberty, less muscle and less facial and body hair compared with other teens
• Small, firm testicles
• Small penis
• Men with Klinefelter syndrome produce little or no sperm
• Enlarged breast tissue (gynecomastia)
• Weak bones
• Low energy levels
• Tendency to be shy and sensitive
• Difficulty expressing thoughts and feelings or socializing
• Problems with reading, writing, spelling or math
Turner’s syndrome
• A condition that affects
only females, results when
one of the X
chromosomes (sex
chromosomes) is missing
or partially missing.
Signs and symptoms
• short height, failure of the ovaries to develop and heart defects.
• inability to conceive a child without fertility treatment.
• Sexual development that "stalls" during teenage years.
• Broad chest with widely spaced nipples.
• Wide or web-like neck
• Low-set ears.