Year I/Committee II

MEDICAL BIOLOGY and GENETICS

Genetic concepts
Mendel’s Principles of Inheritance
Asst. Prof. Dr. Oya Akça
Istanbul Atlas University-Faculty of Medicine
Department of Medical Biology and Genetics
2024-2025
• A diploid organism contains two copies of every
gene (excepting those carried on the sex
chromosomes).
• One copy of each gene is inherited from each
parent.
• These gene copies separate during the formation
of haploid germ cells and are reunited at
fertilization.
• The individual copies of a particular gene are called
alleles.
 Mendelian Inheritance
• Mendelian inheritance refers
to the inheritance of traits
controlled by a single gene
with two alleles
• The pattern of inheritance of
Mendelian traits depends on
whether the traits are
controlled by genes on
autosomes, or by genes on
sex chromosomes.
Mendelian Inheritance
• Autosomal traits are
controlled by genes on
one of the 22 pairs of
human autosomes.
• Autosomal traits are
inherited in the same
way, regardless of the
sex of the parent or
offspring.
• Traits controlled by
genes on the sex
chromosomes are called
sex-linked traits.
Gregor Mendel and Laws of Inheritance
• The way in which traits
are passed from one
generation to the next-
and sometimes skip
generations-was first
explained by Gregor
Mendel.
• Mendelian inheritance
refers to patterns of
inheritance that are
characteristic of
organisms that
reproduce sexually.
Monohybrid cross
• A monohybrid cross is a breeding
experiment between P generation
(parental generation) organisms that
differ in a single given trait.
• Mendel mated two contrasting
varieties, a process called
hybridization
• The true-breeding parents are the P
generation
• The hybrid offspring of the P
generation are called the F1
generation
• When F1 individuals self-pollinate or
cross-pollinate with other F1 hybrids,
the F2 generation is produced
Monohybrid cross
Mendelian Inheritance
• By experimenting with pea plant breeding through monohybrid crossing,
Mendel developed three principles of inheritance that described the
transmission of genetic traits, before anyone knew genes existed.
1. Unit Factors in Pairs
• Genetic characters are controlled by unit factors existing in pairs in individual organisms.
• A specific unit factor exists for each trait

• Example; Stem height

Unit factors: tall stem (T) and dwarf stem (t)

• Each diploid individual has two unit factors, one of which was inherited from each parent.
• Factors occur in pairs; therefore, three combinations are possible: two tall, two dwarf or one
of each.
• The combination of inherited traits determines stem height

TT, tt, Tt
• What is a UNIT FACTOR according to our knowledge today?
2. Dominance/Recessiveness
• When two different alleles of a gene are
present, one may show its effect while
the other may be masked.
• For example, Tt plants have a tall allele T
and a dwarf allele t, but are
phenotypically tall.
• An organism with alternate forms of a
gene will express the form that is
dominant
• The trait that is always apparent (tall)
is dominant to the trait that is not
always apparent (dwarf, recessive).
3. Segregation

• During the formation of gametes,

the paired unit factors separate
randomly so that each gamete
receives one or the other with equal
likelihood.
• In other words, when sperm and
eggs are formed, one of each allelic
pair is randomly distributed to each
gamete.
• For example, a Rr plant makes
pollen or eggs, each randomly
receives either the R allele or
the r allele
 Dihybrid cross

• Mendel’s dihybrid cross

revealed his 4th
postulate
• Designed experiments
in which he examined
two characters
simultaneously.
• Such a cross, involving
two pairs of
contrasting traits, is
called a dihybrid cross,
or a two-factor cross.
Klug, W. S., Cummings, M. R., Spencer, C. A., Palladino, M. A., & Killian, D. (2019). Concepts of genetics.
Dihybrid cross

• If pea plants having yellow

seeds that are also round
were bred with those having
green seeds that are also
wrinkled; F1 offspring are all
yellow and round, then;
• It is apparent that yellow is
dominant to green, and that
round is dominant to
wrinkled.
4. Independent assortment
• During gamete formation,
segregating pairs of unit factors
assort independently.
• In other words, segregation of
2 alleles at one genetic locus
has no effect on the
segregation of 2 alleles at
another locus (unless linked).
• For example, the assortment of
yellow and green alleles has no
effect on the assortment of
round and wrinkled alleles, and
vice versa.
4. Independent assortment

Independent assortment
describes how different
genes independently
separate from one
another when
reproductive cells
develop.
It is a matter of chance
which member of a
homologous pair goes to
which daughter cell at
anaphase I.
Mendelian inheritance

• Mendelian inheritance
refers to the kind of
inheritance you can
understand more simply as
the consequence of a single
gene.
 Important Terms
• Alleles – alternative forms of genes (plant could have alleles for tall or
short)
• Locus- the location of a particular gene on a chromosome
• A character is an observable physical feature, such as flower color.
• A trait is a particular form of a character, such as purple flowers or white
flowers.
• A heritable trait is one that is passed from parent to offspring.
• Dominant Trait – trait that is seen more frequently. Upper case letters.
• Recessive Trait – trait that is “hidden”. Lowercase letters
• Phenotype – way an organism looks (ex. Tall or short)
• Genotype – gene combination. Written using letters (ex: TT, Tt, tt )
• The genetic constitution of an individual with respect to a particular trait
is referred to as the genotype, whereas the corresponding physical
manifestation of the trait is the phenotype.
• Homozygous refers to the two alleles being identical.
• Heterozygous refers to the two alleles having a different nucleotide
sequence, which may be caused by mutations.
Studying Inheritance Patterns
• Traits are passed down in families in different patterns.

• There are two very useful tools for studying how traits are passed from one generation to the next.
One tool is a pedigree, and the other is a Punnett square.

• Pedigrees can illustrate these patterns by following the history of specific characteristics, or
phenotypes, as they appear in a family.
Pedigree
• The chart below is called a pedigree. A pedigree shows how a trait is passed
from generation to generation within a family.
• A pedigree can show, for example, whether a Mendelian trait is an autosomal
or X-linked trait.
• It can also be used to infer the genotype of different members of the family.
The first affected individual to be identified in
the family is termed the proband.
 Punnett Square
• A Punnett square is a chart that allows you to easily determine the expected ratios
of possible genotypes in the offspring of two parents.
Four modes of Mendelian Inheritance

• Autosomal dominant
• Autosomal recessive

• X-linked dominant
• X-linked recessive
Autosomal Dominant
Autosomal dominant traits
are expressed in both the
heterozygous and the
homozygous states

Only one copy of a disease

allele is required for an
individual to be susceptible
to expressing the
phenotype.
Autosomal Dominant
An affected individual has an
affected parent (unless the
affected is expressing a new
mutation).

Actually, many human

dominant disorders are not
“pure” dominants; the
homozygote may actually be
more severely affected, and
even may not survive, so
clinically affected individuals
will be heterozygotes.
A number of features in a pedigree help identify autosomal dominant
inheritance:
➢Because affected individuals must receive a disease-causing gene from
an affected parent, the disease is typically observed in multiple
generations of a pedigree.
➢Skipped generations are not typically seen because two unaffected
parents cannot transmit a disease-causing allele to their offspring (an
exception occurs when there is reduced penetrance).
➢Because these genes are located on autosomes, males and females are
affected in roughly equal frequencies. The transmission of the trait is
sex-independent.
Autosomal Dominant
Autosomal dominant alleles are relatively rare in populations, so the typical mating pattern is a heterozygous affected individual (Aa
genotype) mating with a homozygous normal individual (aa genotype)
An affected parent has a 50% chance of passing the affected allele to their offspring.
The recurrence risk is thus 50%, and half the children, on average, will be affected with the disease.
If both parents are heterozygous, the recurrence risk is 75%.
Recurrence risk
• The recurrence risk is the probability that the offspring of a couple will
express a genetic disease.
• For example, in the mating of a normal homozygote with a heterozygote
who has a dominant disease-causing allele, the recurrence risk for each
offspring is 1/2, or 50%.
• It is important to remember that each reproductive event is statistically
independent of all previous events.
• Therefore, the recurrence risk remains the same regardless of the number
of previously affected or unaffected offspring.
• Determining the mode of inheritance of a disease (e.g., autosomal dominant
versus autosomal recessive) enables one to assign an appropriate
recurrence risk for a family.
Autosomal Dominant

• But ratios may be less because of reduced penetrance

• The probability of a gene being expressed phenotypically is called penetrance.
If the expression is below 100%, it means that this gene does not show full
penetrance, it shows lack of penetrance.
• For example, if the penetrance is 80%, it means that 80 out of 100 people who
carry this gene will develop the disease. More often it applies to autosomal
dominant diseases.
 Autosomal Dominant
• Skipped generations are not typically seen because two unaffected parents
cannot transmit a disease-causing allele to their offspring (an exception may
occur…look nxt page)

Lieberman, M. A., & Ricer, R. (2019). Brs Biochemistry, Molecular Biology, And Genetics. Lippincott Williams & Wilkins.
Autosomal Dominant
Children of someone who is not ill usually cannot be sick; but there are 4 exceptions to
this situation:
1. Incomplete (reduced) penetrance
2. De novo mutation: This condition is not inherited by an autosomal dominant
mutation; tells that it is the result of a mutation that appeared in that person for
the first time in the family. Every autosomal dominant disease starts in a family with
a de novo mutation; however, the family tree may not show a disease that started
in very distant generations.
3. Variable expressivity: This situation is similar to incomplete penetrance. However,
there is a case where the person shows the disease as severe or mild. The classic
example is neurofibromatosis. When a parent who has only cafe au laits passes on
NF1 to their child, the child can become very ill.
4. Mosaicism: It is the condition that the disease occurs with a de novo mutation after
the embryo has formed. Here, the disease has not reached every cell of the
individual, so the person may not show the disease at all or may show it mildly.
 Autosomal Recessive

As autosomal recessive alleles are

clinically expressed only in the
homozygous state, the offspring must
inherit one copy of the disease causing
allele from each parent.

In other words; transmission of the trait

must occur from both parents.
Autosomal Recessive

Such individuals are said to be

homozygous, since both gene copies
are mutated.
Specific mutation in each allele may be
different, but both nevertheless are
mutated.
 Autosomal Recessive

Most commonly, a homozygote is

produced by the union of two
heterozygous (carrier) parents

The parents are both carriers (i.e., they

are heterozygous), having one mutated
copy and one non mutated (wild-type)
copy

The recurrence risk for offspring of such

matings is 25%.
Korf, B. R., & Irons, M. B. (2013). Human Genetics and Genomics, Includes Wiley E-Text. John Wiley & Sons.
Autosomal Recessive

Because these genes are located on

autosomes, males and females are
affected in equal frequencies
Autosomal Recessive

Probably the trait has been in the family for

generations, with many individuals being
heterozygous carriers, but only in instances
where the trait comes together in a
homozygous state does the disorder surface.
• Generations may be skipped in the expression of the disease if all offspring
are heterozygotes.
Autosomal Recessive

Probably the trait has been in the family for

generations, with many individuals being
heterozygous carriers, but only in instances
where the trait comes together in a
homozygous state does the disorder surface.

CONSANGUINITY
• The likelihood of this
occurring is increased if
the parents are related to
one another
(CONSANGUINEOUS), in
which case they both
inherit what may be a rare
recessive allele from a
common ancestor
• Rare recessive disorders are therefore
more common in the offspring of
consanguineous parents,
but not all consanguineous matings
result in recessive disorders and
not all recessive disorders require
consanguinity to be uncovered.
Practice;
X-Linked Inheritance
• Single-gene X-linked traits have a different pattern of inheritance than single-gene
autosomal traits
• Males always inherit their X chromosome from their mother, and they pass on their X
chromosome to all of their daughters, but none of their sons.
• Because males have only one copy of the X chromosome, they are said to be
hemizygous (hemi = “half ”) for the X chromosome.
X-Linked Inheritance
• A mutation on the X chromosome will more likely be expressed in males, who
receive a single X from their mothers and a Y from their fathers.
• Females will express the trait only if they inherit it from both parents, which
will occur much more rarely.
X-linked Recessive Inheritance

• If a recessive disease causing mutation

occurs on the X chromosome, a male will be
affected with the disease.
• Because males require only one copy of the
mutation to express the disease and females
require 2 copies, X-linked recessive diseases
are seen much more commonly in males than
in females.
• If a mother has the trait, all of her sons
should also have it.
X-linked Recessive Inheritance
• Skipped generations are commonly seen because an affected male can transmit
the disease-causing mutation to a heterozygous daughter, who is unaffected
but who can transmit the disease-causing allele to her sons.
• Male-to-male transmission is not seen in X-linked inheritance; this helps
distinguish it from autosomal inheritance.

Course ISBN-13: 978-1-5062-2827-3

X-linked Recessive Inheritance

Females are usually asymptomatic, exception ;

Lyon hypothesis
• Gene dosage and the Lyon hypothesis
The X chromosome is about five times larger
than the Y chromosome, and if females
expressed all of the genes on both X
chromosomes, they would express more genes
than males.
X-linked Recessive Inheritance
To compensate, and keep the
gene dosage equal between the
sexes;
X-inactivation occurs.
One X chromosome in each cell
is inactivated, condensed, and is
known as a Barr body (only a
small piece of the Barr body is
transcriptionally active).
Inactivation is random as to the
origin (maternal or paternal) of
the chromosome.

Course ISBN-13: 978-1-5062-2827-3

X-linked Recessive Inheritance
Most X-linked alleles are expressed on
one of the two X chromosomes in any
specific cell in a female.
A female who is heterozygous for an X-
linked trait will therefore express the
mutant allele in approximately half her
cells and the nonmutant allele in the
other half.
There may be some phenotypic
expression of the trait based on the
mutant allele being expressed in 50% of
cells.

Course ISBN-13: 978-1-5062-2827-3

X-linked Recessive Inheritance
Sometimes there is nonrandom X
inactivation, that is, one X
chromosome is active in more than
50% of cells.
If unequal X-inactivation occurs
(more cells inactivate the paternal X
chromosome as opposed to the
maternal X chromosome or vice
versa), a female may express
symptoms of an X-linked recessive
disorder.
Depending upon how much product
is needed to be healthy, some
females may be mildly affected.
Males are typically affected, with
some variability in severity.
Course ISBN-13: 978-1-5062-2827-3
Manifesting heterozygotes
Normal females have two copies of the X chromosome, so they usually require
two copies of the mutation to express the disease.
However, because X inactivation is a random process, a heterozygous female
will occasionally express an X-linked recessive mutation because, by random
chance, most of the X chromosomes carrying the normal allele have been
inactivated.
Such females are termed manifesting heterozygotes.
Because they usually have at least a small population of active X chromosomes
carrying the normal allele, their disease expression is typically milder than that
of hemizygous males.
X-linked Recessive Inheritance

• Affected male–homozygous normal

female: All of the daughters will be
heterozygous carriers; all of the
sons will be homozygous normal.
• Normal male–carrier female: On
average, half of the sons will be
affected and half of the daughters
will be carriers.
• Note that in this case, the
recurrence rate is different
depending on the sex of the child.
X-linked Recessive Inheritance

• If the fetal sex is known, the

recurrence rate for a daughter is 0,
and that for a son is 50%.
• If the sex of the fetus is not known,
then the recurrence rate is multiplied
by 1/2, the probability that the fetus
is a male versus a female.
• Therefore if the sex is unknown, the
recurrence risk is 25%.
X-linked Dominant Inheritance

There are relatively few diseases whose inheritance

is classified as X-linked dominant.

As in X-linked recessive inheritance, male–male

transmission of the disease causing mutation is not
seen.
X-linked Dominant Inheritance
Heterozygous females are affected.

Because females have 2 X chromosomes (and thus 2

chances to inherit an X-linked disease causing
mutation) and males have only one, X-linked dominant
diseases are seen about twice as often in females as in
males.

Females may express less severe symptoms than males due

to the presence of a corresponding nonmutated allele.

As in autosomal dominant inheritance, the disease

phenotype is seen in multiple generations of a pedigree;
skipped generations are relatively unusual.
X-linked Dominant Inheritance
Affected males will give the disease to their
daughters 100% of the time, but not to
their sons.

Fragile X syndrome is an important

example.
Females are differently affected than
males, and whereas penetrance in males is
100%, that in females is approximately
60%. The typical fragile X patient described
is male.
X-linked Dominant Inheritance
Affected male–homozygous normal female: None of the sons are affected; all of the daughters are affected. Note
that in this case, the recurrence rate is different depending on the sex of the child.
If the fetal sex is known, the recurrence rate for a daughter is 100%, and that for a son is 0%.
If the sex of the fetus is not known, then the recurrence rate is multiplied by 1/2, the probability that the fetus is
a male versus a female. Therefore if the sex is unknown, the recurrence risk is 50%.

Normal male–heterozygous affected female: on average, 50% of sons are affected and 50% of daughters are
affected.
Y-linked inheritance

• Y-linked inheritance is a form of

inheritance for the genes located on the Y
chromosome.
• Y chromosome is smaller than the X
chromosome and thus, carries relatively
fewer genes.
• Apart from the genes for sperm
development, appropriate hormonal
output, and other traits characterizing
males, the Y chromosome also carries
genes other than for sex determination.
Y-linked inheritance
• Hypertrichosis of the ears is an
example of Y-linked
inheritance in humans.
• Hypertrichosis of the ears (or
hairy ears) is a condition
wherein there is a growth of
hair on the outside rim of the
ear.
• Since Y-linked inheritance
involves the Y chromosome, Y-
linked inheritance is passed on
from father to son.
Y-linked inheritance
Mutations of Y-linked genes manifest primarily as male infertility and are
therefore usually not passed on to future generations.
This is changing, however, with the advent of assisted reproduction techniques
that allow those with Y-linked genetic infertility to pass their genetic differences
to future generations.