Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Learning Objectives

11:03 Genetics Dr Hasan Akbar Khan 73 11:03 Genetics Dr Hasan Akbar Khan 74

11:03 Genetics Dr Hasan Akbar Khan 75 11:03 Genetics Dr Hasan Akbar Khan 76
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

77 Karyotype
Definition

•A photographic
1 2 3 4 5

arrangement of a
Karyotyping
complete set of 6 7 8 9 10 11 12

chromosomes of a
13 14 15 16 17 18
cell or organism
19 20 21 22 X Y

Genetics Dr Hasan Akbar Khan 09:03 09:03 Genetics Dr Hasan Akbar Khan 78

Karyotype

• A karyotype is the number and appearance of chromosomes in

the nucleus of a eukaryotic cell.

• The term is also used for the complete set of chromosomes in

a species, or an individual organism

09:03 Genetics Dr Hasan Akbar Khan 79 10:02 Genetics Dr Hasan Akbar Khan 80
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Karyotyping
History of Karyotype
• Karyotypes describe the chromosome count of an organism, and
what these chromosomes look like under a light microscope.
• Chromosomes were first observed in plant cells
Attention is paid to
by Carl Wilhelm von Nägeli in 1842. • their length,

• the position of the centromeres,

• In Animal (Salamander) cells was described
• banding pattern,
by Walther Fleming, the discoverer of mitosis, in
• any differences between the sex chromosomes,
1882. • any other physical characteristics
09:03 Genetics Dr Hasan Akbar Khan 81 09:03 Genetics Dr Hasan Akbar Khan 82

Human karyotype
Karyotyping
• The normal human karyotypes contain:

• 22 pairs of autosomal chromosomes and • Karyotyping is a laboratory procedure that allows us to examine
• One pair of sex chromosomes. 1 2 3 4 5 a patient’s set of chromosomes.
• Normal karyotypes for: • “Karyotype” also refers to the actual collection of chromosomes
• females contain two X chromosomes and 6 7 8 9 10 11 12 being examined.
are denoted 46,XX;
• Examining these chromosomes through karyotyping allows us
• males have both an X and a Y 13 14 15 16 17 18
to determine whether there are any abnormalities or structural
chromosome denoted 46,XY.
19 20 21 22 X Y
09:03 Genetics Dr Hasan Akbar Khan 83
problems.
09:03 Genetics Dr Hasan Akbar Khan 84
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

How the Test Is Performed

• Sampling;

• The first step in karyotyping is to take a sample of cells.

• The sample cells can come from a number of different

tissues, including bone marrow, blood, amniotic fluid, or
placenta.

• After the sample has been taken, it is placed in a laboratory

dish that allows the cells to grow.
09:03 Genetics Dr Hasan Akbar Khan 85 09:03 Genetics Dr Hasan Akbar Khan 86

09:03 Genetics Dr Hasan Akbar Khan 87 09:10 Genetics Dr Hasan Akbar Khan 88
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

09:03 Genetics Dr Hasan Akbar Khan 89 09:03 Genetics Dr Hasan Akbar Khan 90

How the Test Is Performed

• These stained cells are examined under a microscope for potential
abnormalities, including:

• extra chromosomes

• missing chromosomes

• missing portions of a chromosome

• extra portions of a chromosome

• portions that have broken off of one chromosome and reattached to

another
09:10 Genetics Dr Hasan Akbar Khan 91 09:03 Genetics Dr Hasan Akbar Khan 93
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

How the Test Is Performed Interpretation

• The laboratory technician can see the chromosomes’
• A normal test result will show 46 chromosomes,
• shape,
• size, and • 44 of which are autosomes (which are unrelated to
• number. determining gender) and;
• This information is instrumental in determining whether or not • Two of which are sex chromosomes.
any genetic abnormalities are present.
• These sex chromosomes determine one’s gender: females have
two X chromosomes, while males have one X chromosome and one
Y chromosome.

09:03 Genetics Dr Hasan Akbar Khan 94 09:03 Genetics Dr Hasan Akbar Khan 95

09:03 Genetics Dr Hasan Akbar Khan 96 09:03 Genetics Dr Hasan Akbar Khan 97
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

A. Chromosome Staining & Structure

• Metaphase chromosome spread
• Staining techniques
• G-banding
• R-banding
• Q-banding

09:03 Genetics Dr Hasan Akbar Khan 98 09:03 Genetics Dr Hasan Akbar Khan 100

A. Chromosome Staining & Structure Staining

• Centromere Position Banding patterns can be visually identified on chromosomes after
staining.
• Metacentric

• Submetacentric Traditional Types

• G-Banding – Giemsa stain
• Acrocentric; P & q arms • Q-Banding – Fluorescent stain
• Telocentric • R-Banding – Reverse Giemsa stain

• Centromere & telomere structures New Type

• Fluorescence In Situ Hybridization techniques

09:03 Genetics Dr Hasan Akbar Khan 101 09:14 Genetics Dr Hasan Akbar Khan 102
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Procedure of staining Procedure of staining

• Q-Banding : Chromosomes are treated with
• G-Banding : Chromosomes are treated with an enzyme quinacrine mustard and patterns are observed by
(trypsin) to digest some chromosomal proteins. Chromosomes placing the sample under a special type of
are then exposed to Giemsa stain, which consists of a mixture ultraviolet light microscope. The chromosomes
of dyes and results in darkly stained G bands which are visible will show bright fluorescent bands.
under a microscope.

quinacrine mustard a
nitrogen mustard
derived from
mepacrine and used as
a stain for
chromosomes
09:03 Genetics Dr Hasan Akbar Khan 103 09:03 Genetics Dr Hasan Akbar Khan 104

Procedure of staining
• R-Banding : Chromosomes are treated with Diploid & Haploid
acridine orange and observed with a light
microscope. The result is a darkly stained
centromere region of the chromosome. • Ploidy: It denotes the number of chromosomal set (n) in a cell.

• Haploid cells contain only one set of Chromosomes (n).

• Diploid, as the name indicates, contains two sets of

chromosomes (2n).

• Haploid cells are formed by the process of meiosis.

• Diploid cells undergo mitosis

09:03 Genetics Dr Hasan Akbar Khan 105 09:03 Genetics Dr Hasan Akbar Khan 106
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Aneuploidy

Aneuploidy is the presence of an abnormal

number of chromosomes in a cell, for
example a human cell having 45 or 47
chromosomes instead of the usual 46
09:03 Genetics Dr Hasan Akbar Khan 107 09:03 Genetics Dr Hasan Akbar Khan 108

Pedigree, Proband, Proposita,

Propositus, Interpretation of
Pedigree

Genetics Dr Hasan Akbar Khan 09:03 109

09:18 Genetics Dr Hasan Akbar Khan 110

Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Pedigree

A Pedigree is a graphic representation of the family health history

that illustrates relationships and highlights traits that cluster in
families and across generations.

Pedigree is also defined in terms of a genetic representation of a

family tree that diagrams the inheritance of a trait or disease
through several generations and shows relationships between
members.
09:03 Genetics Dr Hasan Akbar Khan 111 09:03 Genetics Dr Hasan Akbar Khan 112

Pedigree Pedigree

• Age at onset and symptoms in affected relatives should be

• Accurate documentation of the family history is an essential part of

genetic assessment. documented.

• Family pedigrees are drawn up and relevant medical information on • Specific questions should be asked about abortions, stillbirth,

relatives sought. infant death, multiple marriages and consanguinity as this

• It is important to record full names and dates of birth of relatives on information may not always be volunteered.

the pedigree, so that appropriate hospital records can be obtained if

necessary.
09:03 Genetics Dr Hasan Akbar Khan 113 09:22 Genetics Dr Hasan Akbar Khan 114
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Pedigree, Consultand Vs Proband

• When a pedigree is drawn, it is usually easiest to start with the

person seeking advice (the consultand).

• This person is seeking genomic health information but does not have

a known diagnosis of the disorder for which s/he is seeking

consultation.

• This person is identified on the pedigree with an arrow but is not

identified in the pedigree legend with the medical disease/disorder.

09:03 Genetics Dr Hasan Akbar Khan 115 09:03 Genetics Dr Hasan Akbar Khan 116

Pedigree, Consultand Vs Proband Pedigree, Proband, Proposito, Proposita

• The consultand can be healthy or a person with medical conditions • It is not uncommon for an individual to be both a consultand and
but not currently diagnosed with a condition warranting evaluation. a proband.

• In contrast, the Proband is the affected individual who manifests • For example, a Caucasian female presenting with a history of
symptoms of a particular disease/condition that brings the family to
breast cancer diagnosed at age 35 may have genetic testing
medical attention
that reveals she has inherited a hereditary breast

cancer syndrome (BRCA) mutation.

• Proposito (male proband), or Proposita (female proband)

09:03 Genetics Dr Hasan Akbar Khan 117 09:03 Genetics Dr Hasan Akbar Khan 118
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Pedigree Pedigree
Symbols Symbols

09:03 Genetics Dr Hasan Akbar Khan 119 09:03 Genetics Dr Hasan Akbar Khan 120

Duchenne Muscular Dystrophy

Pedigree

09:28 Genetics Dr Hasan Akbar Khan 122 09:03 Genetics Dr Hasan Akbar Khan 123
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Duchenne Muscular Dystrophy

X-linked recessive

09:03 Genetics Dr Hasan Akbar Khan 124 09:33 Genetics Dr Hasan Akbar Khan 125

Rickets
X-linked Dominant

09:03 Genetics Dr Hasan Akbar Khan 126 09:37 Genetics Dr Hasan Akbar Khan 127
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Xeroderma Pigmentosum
Autosomal Recessive

09:03 Genetics Dr Hasan Akbar Khan 128 09:03 Genetics Dr Hasan Akbar Khan 129

Huntington’s Disease
Autosomal Dominant

09:03 Genetics Dr Hasan Akbar Khan 130 09:03 Genetics Dr Hasan Akbar Khan 131
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Mitochondrial Inheritance
• Mitochondrial DNA disease is caused by a mutation in your
Mitochondrial
mitochondrial DNA. Inheritance

• Most cases of mitochondrial DNA disease will have been maternally

inherited which means the mutation has been passed down from
the mother to child.

• This is because we inherit our mitochondrial DNA from our mothers

only.

09:03 Genetics Dr Hasan Akbar Khan 133 09:03 Genetics Dr Hasan Akbar Khan 134

Penetrance

Penetrance describes whether gene carriers of

a condition develop features of the condition
Penetrance, Codominance and
Polygenic
The proportion of genotypes that actually show

Genetics Dr Hasan Akbar Khan 09:03 136

expected phenotypes is called penetrance.
09:03 Genetics Dr Hasan Akbar Khan 137
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Penetrance
Complete Penetrance
• If 100% of individuals carrying a particular genotype express the associated trait,
the genotype is said to show complete penetrance e.g. Neurofibromatosis type
1 (NF1)

Reduced Penetrance
• The penetrance is said to be reduced if less than 100% of individuals carrying a
particular genotype express associated traits, and is likely to be caused by a
combination of genetic, environmental and lifestyle factors.
• BRCA1 is an example. By age 70, the mutation is estimated to have a breast
cancer penetrance of around 65% in women.
09:03 Genetics Dr Hasan Akbar Khan 138 09:03 Genetics Dr Hasan Akbar Khan 139

Codominance

When two alleles for a trait are equally expressed with neither
being recessive or dominant, it creates codominance.

Examples of codominance include a person with type AB blood,

which means that both the A allele and the B allele are equally
expressed.

09:03 Genetics Dr Hasan Akbar Khan 140 09:03 Genetics Dr Hasan Akbar Khan 141
Genetics Dr Hasan Akbar Khan 31st July 24 7/31/2024

Polygenic
• Polygenic Inheritance refers to an inheritance of a single phenotypic
trait controlled by multiple independent genes

• OR

• Polygenic inheritance occurs when many genes, each with a small

effect, control the expression of a trait

• Height, hair color, eye color, and skin color are examples of
polygenic traits
09:03 Genetics Dr Hasan Akbar Khan 142 09:03 Genetics Dr Hasan Akbar Khan 143