Lecture ‫الجامعـــة التقنيـــة الجنوبيــــة‬

3rd Stage
01 ‫كلية التقنيات الصحية والطبيـة‬
Medical Genetics
2021-2022 ‫قســـم التحليـــالت المرضيــــة‬

Medical Genetics
Introduction

Dr. Hussam S. Aziz

MSc. Medical Genetics
Medical Genetics

 Genetics: is the branch of biology that deals with the structures

of genetic material and the transmission of characters from
one generation to another

 Medical Genetics: is the branch of medical sciences that deals

with heritable (genetic) diseases in terms of transmission,
pathogenesis, diagnosis, treatment and prevention

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Branches of Medical Genetics

 Cytogenetics

 Molecular genetics

 Biochemical genetics

 Epigenetics

 Clinical genetics

 Population genetics 3
Branches of Medical Genetics
 Cytogenetics: deals with chromosomal structure and
abnormalities at the chromosomal level

 Molecular Genetics: deals with nucleic acids structures and

abnormalities at the molecular level (one or few nucleotides)

 Biochemical Genetics: deals with the biochemical changes in

the body that are associated with genetic disorders

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Branches of Medical Genetics
 Epigenetics: deals with the effects of external (environmental)
factors on genes expression

 Clinical Genetics: deals with clinical presentation and

transmission of genetic diseases in families

 Population Genetics: deals with the frequency of genetic

diseases and mutations at the population level

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History

Development Of Genetics

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Development of Genetics Across History
Dawn of civilization
… humankind has recognized the
influence of heredity and applied its
principles to the improvement of
cultivated crops and domestic
animals

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Development of Genetics Across History
An old carvings show cross-
pollination of date palm trees

A Babylonian tablet more than 6,000 years

old shows pedigrees of horses

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Early Theories

Hippocrates (father of medicine), 460- 375 BCE,

hypothesis of pangenesis

Aristotle, 384–322 BCE, emphasized

the importance of blood in heredity

Preformation theory
(until 18th century)
Theory of Epigenesis

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Development of Genetics

Most of the mechanisms of heredity, however, remained

a mystery until the 19th century, when genetics as a
systematic science began 10
Development of Microscope
 14th century spectacles first made in Italy

 1590 Two Dutch spectacle-makers, a father-and-son team,

Hans and Zacharias Janssen, created the first compound
microscope

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Development of Microscope
 1667 Robert Hooke's famous "Micrographia" is published,
which outlines Hooke's various studies using the microscope

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Development of Microscope
 1675 Anton van Leeuwenhoek, used a microscope with one
lens to observe insects and other specimen

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Development of Microscope

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Electron Microscope
 1931 Max Knoll and Ernst Ruska invented the first electron
microscope

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Cell Theory
 1665 the term Cell (cella=room) was first used by Robert
Hooke (British)
 1839 Cell theory was proposed, independently,
by Theodor Schwann, Matthias Jakob Schleiden
and Rudolf Virchow

 Cell Theory
 All living organisms are composed of one or more cells
 Cell is the basic unit of life
 New cells arise from existing cells
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Gregor Johann Mendel (Father of Genetics) 1822-1884

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Gregor Johann Mendel (1822-1884)
 20th Jul,1822 – 6th Jan, 1884
 Austrian monk and scientist
 Father of modern genetics
 Studied the segregation of traits in pea plant
 Experiments 1856 - 1863
 Mendel’s laws of inheritance

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Gregor Johann Mendel (1822-1884)

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Discoveries
 1835 botanist Hugo von Mohl, described cell division
 1878 Walter Flemming used the term mitosis
 1876 Oscar Hertwig described meiosis
 1905 the term meiosis was introduced by J.B. Farmer and J.E.
Moore
 1902 “Chromosomal theory of inheritance”
was proposed by Walter Sutton and
Theodor Boveri

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The DNA Era
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Discover DNA Structure
 1869 DNA Structure (nuclein) was identified
by Swiss chemist Johann Fredrich Miescher
 1881 Albrecht Kossel isolated the building
blocks (nucleotides) of nucleic acids:
 Adenine (A)
 Guanine (G)
 Cytosine (C)
 Thymine (T)
 Uracil (U)

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DNA Structure
 1952 a picture of DNA was taken by Rosalind
Franklin using X-ray

 1953 James Watson & Francis Crick

described the double-helix structure of
DNA 24
Invention
 1928 First induced mutation by Lewis John
Stadler by using X-ray with corn

 1977 DNA sequencing was first developed

Frederick Sanger

 1983 PCR was developed by Kary Mullis

 2014 Next Generation Sequencer (NGS)

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Discoveries
 1976 first complete genome sequenced of macrophage MS2

 1990-2003 Human Genome Project

 1996 sheep Dolly, the first cloned animal

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Living Organisms

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Types of Cells

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Viruses

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Some Facts

 Cell is the basic unit of life, 2 types of cells:

 Prokaryotic cells bacteria
 Eukaryotic cells unicellular organisms, multicellular
organisms like fungi, animals, plants, humans
 The genetic material present in the nucleus:
 Surrounded by nuclear membrane in eukaryotes
 Not separated from the cytoplasm in prokaryotes (nucleoid)
 Viruses are intermediate, either DNA or RNA
 Human body contains trillions (10^9) of cells
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Nucleic Acid Structure

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Nucleic Acids
 2 types of nucleic acids:
 Deoxyribonucleic acid (DNA)
 Ribonucleic acid (RNA)
 DNA stores the genetic information
 Arranged as chromosomes in the nucleus and mitochondria
 Every species has a unique number of chromosomes called
the diploid number (2n), e.g. mouse= 42, fruit fly=8
 Human cell contains 46 chromosomes (23 pairs of
chromosomes)
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Medical Genetics

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Medical Genetics

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DeoxyriboNucleic Acids (DNA)

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DNA Arrangement

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Medical Genetics

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Human Genome (Karyotype)

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DNA Arrangement in Chromosomes

 Double helix
 2 parallel strands
 Continuous molecule
 Supercoiled
 Wrapped on Histone protein
 Nucleosomes

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DNA Arrangements

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DeoxyriboNucleic Acid (DNA)
 Stores the genetic information in the nucleus
 Polymer of nucleotides
 Arranged as continuous, double helix molecule
 Measuring unit is base pair (bp)
 Human genome consists of about 3 billion
(10^9) bp
 DNA also in presents in the mitochondria

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DNA Sizes

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Nucleotide
 Building block of nucleic acids
 Consists of:
 Nitrogenous base
 Pentose sugar
 Phosphate group
 5 types of nitrogenous bases
 Sugar is:
 Deoxyribose in DNA
 Ribose in RNA

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Nitrogenous Bases
• Purines (2 rings)
– Adenine A (DNA & RNA)
– Guanine G (DNA & RNA)

• Pyrimidines (1 ring)
– Cytosine C (DNA & RNA)
– Thymine T (DNA only)
– Uracil U (RNA only

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Pentose Sugar
 Pentose: 5 carbon atoms
 Carbon atoms are numbered 1' – 5' (' prime)
 Deoxyribose in DNA
 Ribose in RNA

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Phosphate Groups
 1, 2, or 3 phosphate molecules can be added to free
nucleotides
 Nitrogenous Base + Sugar = Nucleoside
 Nitrogenous Base + Sugar + Phosphate = Nucleotide

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Nomenclature

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DNA Nucleotides

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Nucleotides Arrangement in DNA
 Nucleic acids are polymers of
nucleotides

 In DNA and RNA, nucleotides are

linked together by their sugar and
phosphate groups to form
sugar--phosphate backbone

 Nitrogenous bases remain free

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Nucleotides Arrangement in DNA
 Nucleotides are linked together by
Phosphodiester Bonds
 Every nucleotide is linked with:
 the previous nucleotide at its sugar
carbon atom number 5'
 the next nucleotide at its sugar
carbon atom number 3'

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Nucleotides Arrangement in DNA

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Nucleotides Arrangement in DNA
 This arrangements creates 2
ends to the nucleic acid:
 5' end
 3' end

 Nucleic acids sequence is read

in the 5' end  3' end
direction

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Nucleotides Arrangement in DNA

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Base Pairing in DNA
 DNA molecule consists of 2 strands

 Nitrogenous bases in one strand

pair with the bases in the other
strand by hydrogen bonds

 This pairing holds the two strands

together

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Base Pairing in DNA
 Base pairing is complementary, that:

 Adenine pairs with Thymine by 2

hydrogen bonds (A=T)

 Cytosine pairs with Guanine by 3

hydrogen bonds (C≡G)

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Base Pairing in DNA
 This arrangement makes the 2 strands of DNA:
 Complementary to each other

 Run in opposite directions (antiparallel)

 Gives DNA more stability

 Hydrogen bonds break by heating

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Base Pairing in DNA

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DNA Structure (Summary)

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RiboNucleic Acids (RNA)

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Ribonucleic Acid (RNA)
 Single stranded nucleic acid
 Involved in the process of protein synthesis
 3 main types:
 Messenger RNA (mRNA)
 Transfer RNA (tRNA)
 Ribosomal RNA (rRNA)
 Presents in the nucleus and cytoplasm
 Bases: Adenine, Cytosine, Guanine, Uracil
 Pentose sugar is: Ribose
 Other types of RNA: miRNA, snRNA, siRNA, etc. 62
Messenger RNA (mRNA)
 Single stranded
 Function: carries genetic information
from DNA in the nucleus to the
cytoplasm for protein synthesis
 Size: varies, depends on the gene that
was transcribed from (~500-5000 bases)
 Short lived, less stable than DNA, cells
degrade mRNA after its role finishes

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Transfer RNA (tRNA)
 Folded into clover leaf shape

 Function: carries amino acids to the site

of protein synthesis in the ribosomes

 Size: ~70-90 base

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Ribosomal RNA (rRNA)
 Combines with proteins to form
ribosomes, the site of protein
synthesis
 Size: variable

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Types of RNA

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Function of RNA

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Function of RNA

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Mitochondrial DNA (mtDNA)

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Mitochondrial DNA (mtDNA)
 Mitochondria contain small, double
stranded, circular DNA molecules

 16,569 bp in length

 Each mitochondria has several

copies of the mtDNA

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Mitochondrial DNA (mtDNA)
 Contains 37 genes responsible for the production of proteins
and enzymes required for the mitochondrial function
 mtDNA is inherited from the mother only

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Prokaryotic Nucleic Acids

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Prokaryotic DNA

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Prokaryotic DNA
 Prokaryotes (bacteria) have both, DNA & RNA
 No nuclear membrane separates the DNA from the cytoplasm
 Bacterium has a single circular chromosome
 Additional smaller DNA molecules
 Plasmid: Circular DNA molecules
 Transposon: Linear DNA molecules
 Bacteria can exchange genetic information by plasmids and
transposons
 No histone protein in the DNA
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Prokaryotic DNA

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Viral Nucleic Acids

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Sizes of Various Genetic Elements

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