GENETICS

Mode of
Inheritance
 Objectives
1. To know various patterns of inheritance
2. To know the classification of autosomal
inheritance
3. To be able to use the Punnet square
4. To understand the sex-linked mode of inheritance
5. To understand the nature of inheritance of
mitochondrial genetic disorders.
- Making use of diagrams
showing the ancestral
relationships and
transmission of genetic
traits over several
generations in a family
- The individual in the pedigree that led to
the construction of the pedigree. For
example, a couple consults a medical
geneticist because they have an offspring
who is afflicted with a disease and they
want to find out the mode of transmission of
this disease. When the medical geneticist
constructs the pedigree, the offspring will be
labeled as the proband. Through the
pedigree, the probability of having other
affected children may be determined.
- For every trait governed
by a pair of alleles, these
alleles segregate or
separate during gamete
formation during meiosis
- A pair of alleles for one
trait will segregate or
separate independently of
another pair of alleles for
another trait during meiosis
-A trait whose alleles
that control it are found
in the autosomes (body
chromosomes/ non-sex
chromosomes)
-The gene pair an individual
carries for a particular trait
symbolized with a pair of letters.
By convention, uppercase letter
(eg. A) for a dominant allele and
lowercase letter (eg. a) for the
recessive allele. Any letter in the
alphabet may be used
For a diploid organism with two alleles
in a given gene pair, genotypes may
be written as:
i. Homozygous dominant, i.e. with two
dominant alleles (DD)
ii. Heterozygous, i.e. with a dominant
and recessive allele (Dd). The
individual will show the dominant
phenotype.
iii. Homozygous recessive, i.e. with two
recessive alleles (dd)
-A. The observable trait of an individual
based on its genotype. Examples: red
flower, curly hair, blood types ( i.e. the
blood type is the phenotype)
B. For a typical Mendelian trait, phenotypes
may either be: i. Dominant. A trait that
requires at least one dominant allele for the
trait to be expressed, e.g. Dd ii. Recessive. A
trait that requires two recessive alleles for
the trait to be expressed.
-A trait that is expressed
due to specific
environmental conditions
(i.e. having hair that is
dyed of a different color)
and is not due to the
genotype.
-Also known as monozygotic twins,
which are derived from a single
fertilization event. After the first
cleavage or cell division of the
zygote, the cells or blastomeres
separate and become
independent blastocysts implanted
in the mother’s uterus.
-Twins that are derived from
separate fertilization events
(two eggs fertilized by two
sperms) within the fallopian
tube, resulting in two
separate zygotes; also known
as dizygotic twins.
 Single Gene Disorders
May be: - Autosomal
- Sex linked:
Y- linked , holandric, hemizygote
X- linked , dominant or recessive
 Modes of Inheritance of Single gene Disorders

Autosomal Sex Linked

Recessive Dominant Y Linked X Linked

Abnormal
homozygous

Recessive Dominant
Normal Heterozygous
homozygous
Normal
Abnormal
Autosomal Inheritance
 Autosomal Inheritance

- This is the inheritance of the gene present on the Autosomes.

Both sexes have equal chance of inheriting the disorder (The

occurrence and transmission of the trait is not affected by sex)

Two types:
Autosomal dominant inheritance, if the gene is dominant.
Autosomal recessive inheritance, if the gene is recessive.

Abnormal
Normal Heterozygous homozygous
homozygous
 Autosomal Dominant Inheritance

- Autosomal dominant inheritance, if the gene is dominant.

- The trait (character, disease) appears in every generation.
- The trait is transmitted by an affected (heterozygous) person
to half the children.
- Unaffected persons do not transmit the trait to their children.

Normal male
Normal female
Disease male
Disease female
 Punnet Square; for AD inheritance (Heteroz.) Affected
Mother
D d

Normal d dD dd
Father
d dD dd

50% Normal
50% Affected
(Heteroz.) Affected
Mother
D d

(Heteroz.) D DD dD 25% Normal

Affected 75% Affected
Father d dD dd
 Autosomal Recessive Inheritance
- The trait (character, disease) is recessive.

- The trait expresses itself only in homozygous state.

- Unaffected persons (heterozygotes) may have affected

childrens (if the other parent is heterozygote) .

- The parents of the affected child maybe related

(consanguineous).

- Males and female are equally affected.

A Punnett square simulates two organisms reproducing sexually,
examining just one of the many genes that get passed on. The
completed square shows every possible way the offspring could inherit
this gene, and what the chances are for each result. Making Punnett
squares is a good way to get started understanding the fundamental
concepts of genetics.
Part 1 Making a Punnett Square
Draw a 2 x 2 grid. ...
Name the alleles involved. ...
Check the parents' genotypes. ...
Label the rows with one parent's genotype. ...
Label the columns with the other parent's genotype. ...
Have each box inherit letters from its row and column. ...
Interpret the Punnett square. ...
Describe the phenotype.
autosomal recessive inheritance
A a
Both Parents Heterozygous:
25% offspring affected Homozygous”
A AA Aa
50% Trait “Heterozygous normal but
carrier”
a Aa aa 25% Normal
Punnett square showing autosomal recessive inheritance:
(1) Both Parents Heterozygous:

25% offspring affected Homozygous”

A a
50% Trait “Heterozygous normal but
A AA Aa
carrier”
25% Normal
a Aa aa

Contd.
 (2) One Parent Heterozygous:
Male

Female A a 50% Off springs normal but carrier

“Heterozygous”
A AA Aa 50% Normal

A AA Aa

_________________________________________________________________________
(3) If one Parent Homozygous:
Male

A A
100% offsprings carriers.
Female a Aa Aa

a Aa Aa
Family tree of an Autosomal recessive disorder
Sickle cell disease (SS)

A family with sickle cell disease -Phenotype

Sex-Linked Inheritance
 Sex – Linked Inheritance

- This is the inheritance of a gene present on the sex

chromosomes.

- The Inheritance Pattern is different from the autosomal

inheritance.

- Inheritance is different in the males and females.

X-Linked Recessive
Sex – linked
inheritance
Dominant
Y- Linked
Y – Linked Inheritance
- The gene is on the Y chromosomes.

- Shows Holandric inheritance. i.e.

The gene is passed from fathers to sons only.

- Daughters are not affected.
e.g. Hairy ears in India.

- Male are Hemizygous, the condition exhibits itself whether

dominant or recessive.
male

X Y*

Female X XX XY*

X XX XY*
 X – Linked Inheritance
• >1400 genes are located on X
chromosome (~40% of them are thought
to be associated with disease phenotypes)
X-linked inheritance in male & female
Genotype Phenotype

Males XH Unaffected

Xh Affected

Females XH/XH Homozygous

unaffected
XH/Xh Heterozygous

Xh/Xh Homozygous
affected
XH is the normal allele, Xh is the mutant allele
- The gene is present on the X - chromosome.

- The inheritance follows specific pattern.

- Males have one X chromosome, and are hemizygous.

- Females have 2 X chromosomes, they may be

homozygous or heterozygous.

- These disorders may be : recessive or dominant.

 X – Linked Recessive Inheritance

- The incidence of the X-linked disease is higher in male than in female.

- The trait is passed from an affected man through all his daughters to
half their sons.
- The trait is never transmitted directly from father to sons.
- An affected women has affected sons and carrier daughters.
(1) Normal female, affected male
Ova
All daughters carriers “not affected,
X X All sons are normal

X* X*X X*X

Y XY XY
(2) Carrier female, normal male:

Ova
50% sons affected,
X* X
50% daughters carriers,

Sperm X XX* XX

Y X*Y XY

(3) Homozygous female, normal male:

- All daughters carriers.
- All sons affected.
 G6PD Deficiency
Prevalence & Heterozygote advantage:

•Prevalence:
• 5-25% in areas endemic to malaria.
• <0.5% in areas nonendemic to malaria.
•Heterozygotes for G6PD deficiency have some
resistance to malaria → survival advantage.
 G6PD Deficiency
Inheritance Risk:
•Each son of a mother carrying a G6PD
mutation has a 50% chance of being affected.
•Each daughter of a mother carrying a G6PD
mutation has a 50% chance of being a carrier
•Each daughter of an affected father will be a
carrier
•Each son of an affected father will be
unaffected.
 X-Linked Dominant Disorders

- The gene is on X Chromosome and is dominant.

- The trait occurs at the same frequency in both males

and females.

- Hemizygous male and heterozygous females express

the disease.
 ** Punnett square showing X – linked dominant type of Inheritance:

(1) Affected male and normal female:

OVA
All daughters carriers, all sons normal.
X X
Sperm
X* X*X X*X

Y XY XY

(2) Affected female (heterozygous) and normal male:

OVA

X* X 50% of either sex is normal

Sperm
X XX* XX

Contd.
Y X*Y XY
 (3) Affected female (homozygous) and normal male:
OVA

X* X*
Sperm

X X*X XX*

Y X*Y X*Y
 X-linked dominant disorder
e.g. Incontinentia pigmenti (IP)

Pedigree pattern
Normal male
Normal female
Disease male
Disease female

Lethal in males during the prenatal period

Lethal in hemizygous males before birth

- Exclusive in females
- Affected female produces affected daughters,
normal daughters, and normal sons in equal
proportions (1:1:1)
 Fragile X Syndrome
FMR1 Mutation
The leading inherited form of mental retardation
X-linked

Cytogenetic marker on the X chromosome @ Xq27.3 “a fragile site” in which the

chromatin fails to condense properly during mitosis

Medicineworld.org: The Fragile X Mental Retardation

Mitochondrial Inheritance
 Mitochondrial Disorders
* The defective gene is present on the
mitochondrial chromosomes.
•Effect generally energy metabolism.
* Effect more those tissues which require
constant supply of energy e.g muscles.
* Shows maternal inheritance:
-affected mothers transmit the disorder
equally to all their children.
-affected fathers do not transmit the
disease to their children.
 Example of Mitochondrial Disorders

Lebers hereditary optic neuropathy

(LHON)
Rapid Optic nerve death  blindness in young adult life

http://ghr.nlm.nih.gov/condition=leberhereditaryopticneuropathy
 Mitochondrial Inheritance

- Affected females transmit the disease to all their children.

- Affected males have normal children.
- Males cannot transmit the disease as the cytoplasm is inherited
only from the mother, and mitochondria are present in the
cytoplasm.