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Genetic of Mendelian


What is Genetic?
. the science studies inheritance and changeability

characteristics of living organisms, Which is include the
study of genes, heredity, and genetic variations

What is an Inheritance? is how the traits, or characteristics, are passed on from
generation to generation
What is an Changeability? to be capable to acquire new characteristic
quality of being changeable depends of genes and

Father of genetic was

Gregor Mendel
Austrian Monk who Experimented with pea plants in the mid
nineteenth century using defined crosses.
Understood that there was something that carried traits from one
generation to the next- FACTOR
Parents pass on to their offspring separate and distinct factors
(today called genes) that are responsible for inherited traits
However humans have long understood that offspring tend to
resemble parents, and have selectively bred animals and plants for
many centuries. They were the first genetists..

Mendel studied Single gene inheritance characteristics

and create three important
Principle we call Mendelian Law of

Mendel studies various alternative characteristics

in the garden pea presented on the square

Law of Dominance
In the monohybrid cross (mating of
two organisms that differ in only one
characteristic), one version is
The Law of Segregation
During the formation of gametes (eggs or sperm),
the two members of gene pairs (alleles) segregate
(separate) from each other.
Half the gametes carry one allele, and the other half carry
the other allele.
Alleles for a trait are then "recombined" at fertilization,
producing the genotype for the traits of the offspring
The Law of Independent
Alleles for different traits distribute/assort
independently of one another in the

Genetic Concepts
Collection of all genetic material of organism

Genotype- the types of genes (Alleles) present

Ex. -(AA/Aa/aa)

Phenotype- How it looks like with appearance

Ex. -(yellow, green)

Dominant traits- traits that are expressed

Ex. - (A)

Recessive traits- traits that are covered up

Ex. -(a)

Genetic Concepts
DNA is mutable and a variation in DNA
sequence at a specific place of gene (locus)
is called an allele
Single prevailing allele presents in the
majority of individuals is WILD type
Changed version of s gene is MUTANT
Given set of Alleles at a locus or cluster of
loci on a chromosome is HAPLOTYPE

Genetic Concepts
Diploid organisms contain 2 alleles of
each gene which set in homologous
chromosome. Those 2 alleles are one from
mother one from father.
Alleles can be identical homozygous (AA)
Alleles can be different heterozygous (Aa)
Sometimes they called as Carriers

If only one allele is present hemizygous

Case in males for genes on X and Y chromosomes

Symbols Should be known

P parents
ex. P: AA; aa
G gametes
ex. G: A; a
F1/F2 - Generations
ex. F: AA, Aa, aa
X - hybridization/crossing
ex. Aa x Aa

Law of Dominance
in the first generation
Breeding of pure lines
of the characteristics of
parent is disappeared

The Law of Segregation

Is shown in the second
generation after
breeding of first generation
Individuals the inhibited
characteristic of one of the
parents appeared
With ratio 3 :1

Punnett squares
probability diagram illustrating the possible offspring
of a mating



x bb





Bb x


The Law of Independent Assortment

Genes for different traits (Color (yellow and green) and Shape
(round and wrinkled)) assort independently of one another in the
formation of gametes








9 (R-Y-)



3 (rrY-)


3 (R-yy) :

The Law of Independent Assortment

Ratio of
9 - (R-Y-)
3 - (rrY-)
3 - (R-yy)
1 (rryy)
From 16 organisms
9 have Both of traits Dominant
3 have the first is recessive & second
3 first dominant & second recessive
1 Both of traits recessive

Traits are determined by the genes set

in the chromosomes. A gene is a
segment of DNA that determines a
trait after the expression

parents pass chromosomes on to

offspring in their sex cells: egg and
sperm cells

Genetic Concepts
One pair of Homologous Chromosomes contain one
pair of gene alleles.
Gene for eye
color (blue eyes
- a)
Homologous pair
of chromosomes
are different with
alleles (A or a)
Gene for eye color
(brown eyes - A)
The gene for a particular inherited character resides at a
specific position Locus on homologous chromosome.

Homologous chromosome with double chromatids

How are genes passed on from parent to


Genes in the cell nucleus are

located on 23 pairs of
One set of 23 chromosomes is
inherited from each parent
Therefore, of each pair of genes,
one is inherited from a persons
mother, and one from their father


How do alleles differ?


Dominant trait (allele) expressed irregardless of the second allele.

Recessive trait that is only expressed when the second allele is the same (e.g. blue
eyes are homozygous for the recessive allele).

Genotype & phenotype

How does a genotype ratio differ from the phenotype ratio?

How to analyze the genotype under the

Yellow green


AA x aa

F1: All Yellow

? x aa


Aa x aa

F1: Yellow & Green



Exception of Mendelian inheritance

Intermediate Inheritance (blending):
inheritance in which heterozygotes have a phenotype
intermediate between the phenotypes of the two

Ratio: phenotype


The Importance of the Environment

The environmental influences the expression of
the genotype so the phenotype is altered
Hydrangea flowers of the same genetic variety range
in color from blue-violet to pink, depending on the
acidity of the soil
Arrow plant leaves shape is depend of the water

Multifactorial; many factors, both genetic

and environmental, collectively influence
phenotype in examples such as skin tanning

Gene variability range


Moderate Adaptive norm

Reaction limit

Mendelian patterns of Dominant

and recessive traits

Mendelian patterns of inheritance

More then 2900 diseases are inherited by Mendelian inheritance
Around 84% are caused by the mutation of the gene
Around 16% of diseases are inherited with direct Mendelian

From Approximate 25000 human gene about 8% are implicated in

human genetic disorders.

Around 10% of those single gene disorders are presented after puberty
1% are manifest after reproductive period

Autosomal inheritance
Autosomal inheritance depends on the genes set on the autosomes.
And inherits Male or Female individual equally.
Autosomal Dominant
Autosomal Recessive
Dominant inheritance
These individuals are called
Heterozygotes with one copy of the
altered gene they are affected

Recessive inheritance
Homozygotes must have two copies of the
altered gene to be affected

Pedigree analysis - family tree

Single gene disorders characterizes by their patterns of transmission in
families. To study and obtain transmission and evaluate the revealing
risk Pedigree analysis is used

The extended family depicted in such a pedigrees is kindred;

The member who is the firs in kindred tree is proband;

Brothers and sisters are Sibs;

Family of Sibs forms Sibships;

Parents, Sibs and offspring of the proband creares the First degree

Grandparents and grandchildren, uncles and aunts, nephews and nieces, and half-sibs
creates The Second Degree;

First cousins are Third degree.

Couples who have one or more common ancestors are consanguineous.

If there is only one affected is isolated or sporadic (depending on mutation) case.

Pedigree analysis

Pedigree analysis
Mendelian patterns in human

Widows peak

Attached earlobe

Autosomal dominant trait

Autosomal recessive trait

Classification of genetic
Single Gene Disorders
Alterations in
single genes

Multifactorial diseases

Variants in

+ environment
Chromosome disorders


Single gene disorders

Some medical conditions are caused
by a change in just one or both copies
of a particular pair of genes. These
are called single gene disorders

The three common types of single gene

disorders are called:
Autosomal dominant


Autosomal recessive




Autosomal dominant
Affected gene locus is located in autosomes and around 3700
disease are known
- Dominant inheritance is presented in
- Homozygous (AA) - the most severe form of disease
- Heterozygous (Aa) Less severe form of disease,
incomplete dominance or career.
Disease spectrum in heterozygous-carriers of mutation is broad,
from carrier to lethal.

Characterized by
50% or 100% of vertical transmission
both Male and Female are similarly affected
Incidence of autosomal dominant diseases is 7 in 1000
in case of mild phenotype the mutation is mostly inherited by one of
the parents

Autosomal dominant

Autosomal dominant






Autosomal dominant

Clinical Patterns

Marfan syndrome
Huntington disease
Neurofibromatosis type 1
Cardiomyopathy (hypertrophic)
Skeletal dysplasia
Familial hypercholesterolemia
Familial Adenomatous Polyposis (FAP)
Neurological diseases (ataxias, paraplegia, dystonia,
inherited dementia)
Familial cancer syndromes (breast, colon,

Autosomal dominant
Marfan syndrome
variable expressivity between members of the same family as the
protein coded for has different functions within the body.
tall stature
thin limbs
and fingers;
high risk of

Arachnodactyly (long fingers)

Dislocated len

Achondroplasia - (Autosomal dominant)

A form of dwarfism.
Incidence of one case among every 10,000 birth.
Heterozygous individuals have the dwarf phenotype.
Achondoplasia is caused by a mutation in the fibroblast growth receptor
3 (FGFR3) gene in 4p16.3

Penetrance and Expressivity

Sometimes phenotypic expression of abnormal genotype
may be modified by effects of aging, other surrounding loci
or effect of environment.
This leads the difficulties in diagnosis and pedigree analysis.
The probability of phenotypic
When gene expression is less 100%
called Reduced Penetrance
This is the percentage of predisposition to
Disease when the person is affected
with some degree

The severity of expression of the phenotype
Among the same disease-causing genotype
Variable Expressvity
Even the same kindred, two individuals
carrying the same pathological gene may
have some symptoms in common, but
others quite different depending the location
of start point of disease

Huntingtons disease

A degenerative disease of the

nervous system
Expression if affected by age
(penetrance) and No obvious
phenotypic effect until the individual is
about 35 to 45 years old.

People with Huntington disease

have 36 to more than 120 CAG
repeats in HTT gene located in
The expanded
CAG segment leads to the production of an
abnormally long version of the huntingtin protein.
The elongated protein is cut into smaller, toxic fragments
that bind together and accumulate in neurons, disrupting
the normal functions of these cells.
This process particularly affects regions of the brain
that help coordinate movement and control thinking
and emotions

Neurofibromatosis type1
Characterized by changes in skin coloring
(pigmentation, pigmented lesions) and the growth of
multiple tumors along nerves, neurofibromas, caf au
lait macules in the skin, brain, and other parts of the
Caused by Mutations in the NF1 gene
Incidence of one case among every 35,000 birth
Phenotype is expresses in adults with 100%, but
sometimes Disease characterized with different
penetrance affected by age and heterozygous
genotype from light pigmentic spots to severe form of
tumor disease.

Correlation of genotype and

Different Mutations at the same locus cause
Genetic Heterogeneity
Which expressed in:
Allelic heterogeneity Many loci have more then one
mutant allele with different phenotypic effect.
Gene CFTR which causes Cystic fibrosis has 1400 mutations.
Among them some mutated allele causes the classic forms of cystic
fibrosis with pancreas insufficiency and lung disease, while other
allele cause only lung disease. etc.

Correlation of genotype and

Locus Heterogeneity
some gene has their allelic variation In different locus of
the chromosomes.
Ex. Retinitis pigmentosa has autosomal dominant (14 loci) and
recessive (24 loci), X-linked (5loci).

Correlation of genotype and

Phenotypic Heterogeneity
some gene gives a various phenotype.
Mutations in the LMNA gene cause Emery-Dreifuss muscular
dystopia, cardiomyopathy, premature aging syndrome of progeria

Autosomal recessive
Autosomal recessive disease occurs only in Homozygous
condition (when both allele are mutated) because in
heterozygote one normal dominant allele inhibit or
compensate the effect.
The people with heterozygous genotype are Carriers


Parent who are carriers for the same autosomal

recessive condition have one copy of the usual
form of the gene and one copy of an altered gene


Autosomal recessive






Autosomal recessive

Autosomal recessive
Currently, in human around 4000 autosomal recessive
diseases are known so far
Incidence of autosomal recessive diseases: 2.5 in 1,000
characterized by the wide range of phenotypic spectrum
Recessive Mutations are homozygous or compoundheterozygous
Carrier of heterozygous mutations are clinically unaffected
Parents of an affected child are usually healthy and are carriers
of a heterozygous mutation

The risk for a healthy person to be a genetic carrier of a

recessive disease is 1:10 to 1:200
Risk astimation:
25%, horizontal
Most human genetic
disorders are recessive both sex are similarly

Autosomal recessive

Clinical Patterns

Sickle Cell disease

Cystic fibrosis (1:2,500)

Phenylketonuria (PKU) 1:5,000

Congenital deafness

Batten Disease

Spinal muscular atrophy -1:10,000

Recessive blindness

Maple syrup urine disease

Hemochromatosis - 1:400

A particular form of deafness is inherited as a

recessive trait by Mendelian way of Autosomal
recessive inheritance
Some other type is
inherited by autosomal
dominant way

Cystic fibrosis (Autosomal recessive )

One out of every 2,500 whites of European descent but is
much rarer in other groups.
One out of 25 whites (4% ) is a carrier
Gene codes for a membrane protein that
functions in chloride ion transport
between certain cells and the
extracellular fluid. These chloride
channels are defective or absent.
In result an abnormally high
concentration of extracellular chloride,
which causes the mucus that coats
certain cells to become thicker and
stickier than normal.

Tay-Sachs disease (Autosomal

recessive )
fatal genetic disorder, mostly in children
Caused by a dysfunctional vital enzyme called hexosaminidase-A
(Hex-A), fails to break down brain nerve cells lipids (called GM2
ganglioside) of a certain class.

Sickle-cell disease (Autosomal recessive

Sickle-cell disease is caused by the substitution of a single amino
acid substitution in the hemoglobin protein of red blood cells
Gene mutation affects 1 out of 400 African Americans.

X linked inheritance
In X linked inheritance the gene is
presented only X or Y chromosome

X linked inheritance
The males have only one X chromosome, therefore they are

Females can be heterozygous/careers

X-linked dominant

X-linked recessive
Males with an altered gene on the
X-chromosome are always affected


X-linked recessive inheritance



One copy of an altered

gene on the X
chromosome causes the
disease in a male.

An altered copy on one

of the X chromosome
pair causes carrier
status in a female.

X-linked inheritance where the mother is a carrier











Son (Affecte

X-linked recessive inheritance


Sex-Linked Disorders in Humans

X-Linked recessive inheritance
Examples of X-Linked Recessive

Duchenne muscular dystrophy (DMD) (Becker BMD)
Fragile X syndrome
Fabry disease
Retinitis pigmentosa
Alport syndrome
Hunter syndrome
Ocular albinism

Duchenne muscular dystrophy

affects about one out of every 3,500 males
People with Duchenne muscular dystrophy rarely live
past their early 20s.
The disease is characterized by a progressive
weakening of the muscles and loss of coordination.
People with syndrome have an absence of a key
muscle protein called dystrophin and have tracked the
gene for this protein to a specific locus on the X

Posture changes during progression of

Duchenne muscular dystrophy.

Impairs the body's ability to control blood clotting, which is used to
stop bleeding when a blood vessel is broken.
Haemophilia A (clotting factor VIII deficiency) is the most common
form of the disorder, present in about 1 in 5,00010,000 male births.
aemophilia B(factor IX deficiency) occurs in around 1 in about
20,00034,000 male births

Effects of haemophilia
(a) Bleeding around elbow. (b) A retinal bleed. (c) Repeated bleeds into
joints produce severe arthritis.


Color Blindness In Humans

Numbers That You Should See If You Are In One Of The Following
Four Categories
X-Linked Traits:
1. Normal Color Vision:
A: 29, B: 45, C: --, D: 26
2. Red-Green Color-Blind:
A: 70, B: --, C: 5, D: -3. Red Color-blind:
A: 70, B: --, C: 5, D: 6
4. Green Color-Blind:
A: 70, B: --, C: 5, D: 2

Baldness is an autosomal trait and is apparently influenced by sex hormones after
people reach 30 years of age or older.
In men the gene is dominant, while in women it is recessive. A man needs only one
allele (B) for the baldness trait to be expressed, while a bald woman must be
homozygous for the trait (BB).

What are the probabilities for the children for a bald man and
woman with no history of baldness in the family?

X-linked dominant inheritance

Y-linked inheritance

Y-linked inheritance shows a patters of transmission of the

mutant phenotype from father to son and it never appears
in famales.
Y-linked phenotypic trait is hairy ears.

Rett Syndrome
Rett syndrome is a rare x-linked dominant severe brain disorder
that mostly affects to females. Because it is lethal in hemizygous
The males who survives with this syndrome usually have two X-cromosome
with 47XXY Klinefelter.

Affected about one in 10,000 to 15,000 females

Syndrome caused by spontaneous

mutation in X-linked gene MECP2.
It's believed that the single gene
may influence many other genes
involved in development.

Mosaicism is the presence in an individual or a
tissue that contains at least two cell lines with
genetically different from whole body

It occurs when in the tissue one or two cell

lines undergo mutation and alter genetically

In Somatic mosaicism is occurring

during embryonic development and
maifest as a segmental or partial
Genetic mosaicism is connected to
the X chromosome changes

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