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A B Ref C Ref

Medical Genetics
JORDE B. L. et al.

5th Edition 2016

Course code:- MEDG2602

DNA
Dr. A. B. Almouslem
Associate Professor of
DNA profiles Genetics & Biotechnology

Useful Internet Resources

Dolan DNA Learning Center, Cold Spring Harbor Laboratory (a useful
online resource for learning and reviewing basic principles)
http://www.dnalc.org/
Genetic Science Learning Center (another useful resource for
learning and reviewing basic genetic principles)
http://gslc.genetics.utah.edu/
Landmarks in the History of Genetics
www.genetests.org
http://cogweb.ucla.edu/EP/DNA_history.html
National Human Genome Research Institute Educational Resources
http://www.genome.gov/Education
Online Mendelian Inheritance in Man (OMIM) (a comprehensive catalog
and description of single-gene conditions)
http://www.ncbi.nlm.nih.gov/Omim/
University of Kansas Medical Center Genetics Education Center (a large
number of links to useful genetics education sites)
http://www.kumc.edu/gec/

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Any one of you is able to get his/her

lectures via the Internet by using the
following connection
http://lectures.kalamoon.edu.sy/baset.almouslem/

Cell Biology MEDG1602

Genetics & Molecular Biology MEDG2602

Medical
Course main contents Genetics

 General introduction of medical genetics

 The molecular structure of the gene & gene activity
 Molecular cloning methods
 Molecular tools for studying genes
 The mechanism of transcription in prokaryotes & eukaryotes
 Chromatin structure & its effects on transcription
 Concepts of genomics & proteomics
 Genetic variation, GENE THERAPY
 Autosomal Recessive & dominant inheritance & Mitochondrial inheritance
 Sex-linked inheritance
 Clinical cytogenetics
 Biochemical genetics
 Immunogenetics
 Developmental genetics
 Cancer genetics
 Genetics & Precision medicine, Clinical Genetics & Genetic counseling
 Multifactorial inheritance

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Medical
Assessment Genetics

Assessment Marks
First Test Theoretical exam 6 th week 20
Second Test Theoretical exam 12 th week 20
Activity & Participation 2½
Course Work Activity & Participation 2½ 10
Research Project Presentation 5
Final Exam 16 th week 50
Total 100

ٌ‫انسشيب‬ Medical
Genetics
‫ثسجت رسصُم انذسخبد‬

‫ يٍ أػًبل انسُخ‬%25 ٍ‫ انسشيبٌ أقم ي‬.1

50 ٍ‫ ي‬12½ ٍ‫= أقم ي‬
‫ يٍ ػاليخ‬%25 ٍ‫ انسشيبٌ أقم ي‬.2
50 ٍ‫ ي‬12½ ٍ‫االيزسبٌ انُهبئٍ أقم ي‬
60 = ‫ دسخخ انُدبذ‬.1
)!‫ (يُؼَشَضٌ نذساسخ انًقشس ثبَُخ؟؟‬59- 50 ٍ‫ َدبذ ششؼ‬.2
) F = ‫ (انزقذَش‬50 ٍ‫ دسخخ انشسىة أقم ي‬.3

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ٌ‫انسعىس وانغُبة وانسشيب‬ Medical

Genetics
‫واالنزضاو ثبنًسبظشاد‬
ٌ‫ انزقُذ ثسعىس انًسبظشاد انُظشَخ ارقبءً نهسشيب‬.1
‫ االنزضاو ثًىاػُذ انًسبظشاد انُظشَخ زست انفئبد‬.2
‫سًىنخ‬
‫ االنزضاو ثًىاػُذ االخزجبساد انُظشَخ زست يىػذ انفئبد‬.3 )!
‫ َُسًر ثبنسعىس انؼهًٍ فقػ فٍ زبل انغُبة‬.4
% 10 = ٍ‫اَزاس خؽ‬
-:‫ انسشيبٌ وَسجخ انغُبة يٍ انًقشس‬.5 ‫د ظًٍ ػؽهخ‬
‫زست خذول انسعىس‬
% 4 = ‫ سبػخ‬2 ‫ يسبظشح َظشَخ‬.a
% 15 = ٌ‫انسشيب‬
% 2 = ‫ سبػخ‬1 ‫ يسبظشح َظشَخ‬.b

Medical
Background & History Genetics

1. Today, Human Genetics is for every one

2. It is about our variation rather than about our illnesses
3. It is being recognized as the basis of Medical Science
4. We know for most traits & Illnesses, many genes
interact with each other & with the environment
5. By coming to know our genetic background, we can
control our environments in more healthful ways

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Medical
Background & History Genetics

1. Genetics: is the study of inherited traits & their variation

2. Gene: is a sequence of DNA in the genome that is
required for production of a functional product, be it a
polypeptide or a functional RNA molecule

Red hair & freckles ‫انًُش‬

1. Are variants of a gene
2. The gene encodes a protein
3. Called Melanocortin-1 receptor
4. That controls the balance of
pigments in the skin

Background & History Medical

Genetics

1. Genome ‫خُُىو‬/ٍُ‫ يد‬: The complete DNA sequence, containing the

entire genetic information, of a gamete, an individual, a
population, or a species
2. Genomic medicine: The practice of medicine based on genomic
information:- ‫يًبسسخ انؽت ثبالػزًبد ػهً يؼهىيبد اندُُىو‬
‫كشويىسىو‬
a. Expression profiling to characterize tumors or to define prognosis
in cancer ٌ‫يخؽؽبد انزؼجُش نزسذَذ خصبئص األوساو أو نزسذَذ رشقٍ انسشؼب‬
b. Genotyping of variants in genes involved in drug metabolism or
action to determine an individual’s correct therapeutic dosage
c. Analysis of multiple protein biomarkers to monitor therapy
Indian Muntjak
d. Provide predictive information in presymptomatic individuals has
3. Genomics: is a field of study that uses genome information to
answer questions in health, research, & the environment.
‫كشويىسىو‬
4. Bioethics ‫ األخالقُبد انجُىنىخُخ‬: is a field of study concerned with Human Genome
Y issues of: a. Privacy b. Confidentiality c. Discrimination

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Relationships: From Individuals Medical

Genetics
to Families
1.Genotype: is the allelic makeup of an individual
2.Phenotype: refers to the observable or measureable
expression of the alleles
3.Dominant alleles: expressed when one copy is present
4.Recessive alleles: require two copies for expression
5.Pedigree diagrams enable recessive & dominant traits to
be followed through individuals across multiple
generations of a family

Medical
Genes & Their Environment Genetics

1. The traditional focus of genetics on traits determined by single

genes is giving way to the realization that most genes do not
function alone.
2. Most traits are Multifactorial traits & are determined by multiple
genes & environmental effects.
3. Symptoms of an illness may have an environmental, single-gene
or Multifactorial basis.
Polydactyly = single gene

Hair color = multi-factorial

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Medical
Background & History Genetics

What is Medical Genetics (MG)?

Definition: MG involves any application of genetics to
medical practice such as:-
1. Inheritance of human genetic disorders
2. Analysis of molecular mechanisms of genetic disorders
3. Diagnosis & Treatment of genetic disorders
4. Gene Therapy
5. Genetic Counseling ‫ اسزشبسح وساثُخ‬:
a. Information risks
b. Prognosis
c. Treatment

Medical
Background & History Genetics

Why MG knowledge is important for today’s

health care practitioner? Prevention
1. Genetic disorders make up a large proportion &
of total diseases of human population
2.Modern medicine is placing more emphasis on Effective
the importance of prevention rather than Treatment
treatment
3. Genetics provides a basis for understanding
the fundamental biological makeup of the
organism….. So:-
a. Understanding of disorder
b. Disorder prognosis/process
c. This leads to prevention of the disorder

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Newborn Screening ‫فسص انىنذاٌ اندذد‬

Prevention ‫وقبَخ‬
&
Effective Treatment ‫ػالج فؼَبل‬
1. Siblings Emma & Mathew;
Emma 2. Both inherited Glutaric Acidemia
Mathew ‫ ازًِْعبضُ ان ذَو‬, an error of metabolism
3. Mathew diagnosed 9 months after
birth; it was late for him, so a
protein build up in the basal ganglia
in the brain that controls
movement, so he is nearly crippled
4. But his sister was diagnosed same
day she was born, & went on special
diet so she is normal

Applications of Medical Genetics Medical

Genetics
‫رؽجُقبد انىساثخ انؽجُخ‬
owed, he fathered I. Establishing Identity‫رسذَذ انهىَخ‬:-
)
1. DNA profiling ‫شَب ِكهَخُ انـذَب‬/‫يخؽػ‬, known as DNA fingerprinting.
It was used for identification following the World Trade
Center attack on Sept. 11, 2001, the Tsunami of 2004, &
hurricane Katrina in 2005.
2. DNA profiling can exclude an individual from being Figure.
biologically related to someone else, or from having (
committed a crime. (
3. DNA profiling can be used to characterize living & dead
populations of humans & other organisms revealing
history & ancestry.

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II. Application of DNA Fingerprinting in Forensics ٍ‫ؼت ششػ‬

S1 S2
Chris Semen Randall
Reesh Sample Jones

Suspect-- 1
Suspect Specimen Suspect-- 2
Suspect DNA Fingerprinting DNA Fingerprinting
Victim Comparison Comparison
DNA Fingerprinting S1 S2
DNA_DetectivePC
Inheritance
Agarose of

Applications of Medical Genetics Medical

Genetics
‫رؽجُقبد انىساثخ انؽجُخ‬
III. Health Care ‫انؼُبَخ انصسُخ‬
1. Genetics is changing health care as genetic information is
being incorporated into diagnosis & treatment.
2. The field of Pharmacogenomics is concerned with patient
response to medication based on genotype.
3. Genetic disorders differ from Infectious diseases in:-
a. The recurrence risks are predictable,
b. Pre-symptomatic diagnosis using genetic testing is possible,
c. Characteristic frequencies are observed in different populations
d. Gene therapy may be used to treat or possibly prevent certain
genetic disorders.

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Medical
Background & History Genetics

Types of genetic disorders: 4,000 disorders

1. Chromosome disorders:
a. Number: Down Syndrome
b. Structure: Fragile X Chromosome Syndrome
2. Single gene disorders: 1. Autosomal Dominant
a. Phynylketounuria (PKU) 2. Autosomal Recessive
b. Achondroplasia ‫انىداَخ‬ 3. X-Linked Dominant
c. Hemophilia ‫انُبػىس‬ 4. X-Linked Recessive
3. Multifactorial disorders: 5. Y-linked genes
a. Neural tube defects (Spina
(Spina bifidia
bifidia)) ‫انسُِسُخ انًشقىقخ‬
4. Mitochondrial disorders:
a. Kaerns
Kaerns--Sayre Syndrome Child with Dysmorph

Background & History Medical

Genetics
Continuum of diseases

Influenza Diabetes Cystic fibrosis

Measles Heart disease Hemophilia A
Infectious diseases
Environment Genetic
Cystic fibrosis ٍّ ِ‫رَهَ ُفٌ كُس‬
Definition: Cystic fibrosis (CF) is an inherited disorder that affects the
lungs, pancreas, digestive system, sweat glands, & male fertility.
Mode of inheritance = Autosomal Recessive (aa).
Description: CF affects the body’s ability to move salt & water in &
out of cells. This defect causes the lungs & pancreas to secrete thick
mucus, blocking passageways & preventing proper function.
cause_cystic fibrosis

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Background & History Medical

The clinical impacts of genetic disorder Genetics

ٍّ‫اِثبس انسشَشَخ نالظؽشاة انىساث‬

1. Genetic disorders are rare; health practitioner seldom encounter them

2. But this is becoming un-true……
3. Death percentage among pediatrics due to genetic causes in London:
1914 -----------> 16.5% 1976 ------------> 50%
4. Admission to pediatric hospitals increased (27% were genetic)
5. What proportion of individuals in the population will be diagnosed with
a genetic disorder????????
6. Some genetic disorders are more common in certain ethnic groups:
 Cystic fibrosis very common among Europeans
 Sickle Cell Anemia is especially common among Africans
7. Some disorders are more common among older individuals:
 Colon Cancer, Breast Cancer, Alzheimer Disease
8. It is expected that 3% to 7% of the population will be diagnosed with a
recognizable genetic disorder

Table 1-2. Percentages of Childhood Deaths

in United Kingdom Hospitals Attributable to
Non-genetic & Genetic Causes.

Cause London 1914 London 1954 Newcastle Edinburgh

1966 1976
Non-genetic* %
All causes 83.5 62.5 58.0 50.0
Genetic
Single gene 2.0 12.0 8.5 8.9
Chromosomal - - 2.5 2.9
Multif actorial 14.5 25.5 31.0 38.2

* I nfections, for example.

Data from Rimoin DL, Connor JM, Pyeritz RE, Korf BR: Emery and Rimoin's Principles and
Practice of Medical Genetics. London: Churchill Livingstone, 2007.

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Table 1-3. Approximate Prevalence of Genetic

Disorders in the General Population.
Type of Genetic Disease Lifetime Prevalence ‫اَزشبس‬
per 1000 Persons
Autosomal dominant 3 - 9.5
Autosomal recessive 2 - 2.5
X-linked 0.5 - 2
Chromosome disorders 6- 9
Congenital malformation* 20 - 50
‫انزشىهبد انخهقُخ‬
Total 31.5 - 73

*Congenital = "present at birth" Most congenital malformations are

thought to be multifactorial & therefore probably have both genetic &
environmental components.

Basic Cell Biology/Genome

Structure & Function of Genes & Chromosomes
Cell general structure

Genes/Genome:- Nucleus Lysosome

a. Are basic units of
inheritance RER
b. In chromosomes
c. Consist of DNA Golgi Apparatus
SER

Mitochondria

Principles of Cell Theory

‫يجبدئ انُظشَخ انخهىَخ‬
1. All organisms are made of
cells (unit of structure) Animal cell
2. Cell structure is correlated
to cellular function (unit of All genetic disorders involve
function)
mutations at the cell level

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Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

 Human Somatic Cell = 46 chromosomes

 Male = 44 (Autosomes) + (Sex chromosomes XY)
 Female = 44 + XX
 Somatic cells are Diploids 2n=46 chromosomes karyotyping
 Mitosis: maintains diploid (2n) number of somatic cells
 Meiosis: maintains haploid (n) number of gametes
Human Karyotype
X ‫كشويىسىو‬
A
B
Karyotype: refers to the
order, number & type of
X
chromosomes present C
in an individual.
D E
Y ‫كشويىسىو‬
F G
Y

Human Genome Composition Medical

ٌ‫رشكُت اندُُىو انجشش‬ Genetics

Nearly 23,000 genes & traits of which nearly:-

a. 21,000 genes are autosomal
b. More than 1200 genes are X-linked
c. 59 genes are Y-linked
d. 37 genes are in the mitochondrial genome

Human Genome is composed of two parts:

1.Nuclear genome (nDNA) = 99.9%
2.Mitochondrial genome (mtDNA) = 0.01%

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The Human Genome: Gene Structure & Function

‫ ثُُخ ووظُفخ انًىسثخ‬:ٌ‫اندُُىو انجشش‬
1. INFORMATION CO NTENT OF THE HUMAN GENOME ٌ ‫يسزىي انًؼهىيبد فٍ اندُُىو انجشش‬
Two questions
‫ ػذد انًىسثبد يسذود‬.1 1. Number of genes is limited.
ً‫ وظبئف انخالَب أكثش رؼقُذا‬.2 2. Functions of cells are more
complicated.
Dilemma ‫ يؼعهخ‬solved:
solved:--
1. First, many genes are
‫وظبئف انخالَب‬ capable of generating
multiple different proteins
2. Second, individual proteins
‫شجكخ اندُُبد‬ do not function alone. They
form elaborate networks of
functions ‫ شجكخ يُسقخ يٍ انىظبئف‬,
‫ثشورُىو‬ involving many different
proteins & responding in a
coordinated fashion to many
‫خُُىو‬ different genetic,
Proteome: orchestrates the many functions of cells, organs, & the
Proteome developmental, or
entire organism, as well as their interactions with the environment. environmental signals
‫ إخًبنٍ انجشورُُبد انً ُظًخ نًدًم وظبئف انخالَب واألػعبء‬:‫انجشورُىو‬
‫ وكزنك رفبػههى يغ انجُئخ‬, ‫وكبيم انًزؼعُخ‬

The Human Genome: Gene Structure & Function

‫ ثُُخ ووظُفخ انًىسثخ‬:ٌ‫اندُُىو انجشش‬
2. GENE ORGANIZATION AND STRUCTURE ‫رُظُى انًىسثخ وثُُزهب‬
The genes are:-
1. Located throughout the genome chromosomes ‫يىخىدح فٍ أسخبء صجغُبد اندُُىو‬
2. But tend to cluster ‫ ردًغ‬in some regions & on some chromosomes
3. Be relatively sparse ‫يجؼثشح‬/‫ قهُهخ‬in other regions or on other chromosomes
11- ٍ‫ انصجغ‬134
134..45 Mb

‫ػبئهخ انًىسثبد‬
350 Olfactory functional OR genes
β-‫انشجُهخ ثخعبة‬
‫يىسثبد زس انشى‬

Figure. Gene content on chromosome 11

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Structural Features of a Typical Human Gene ‫انخصبئص انجُُىثخ نًىسثخ ثششَخ‬

‫ثذء انُسخ‬
‫إَكسىَبد‬
‫كىدوٌ اإلَقبف‬
DNA
‫يؼضاص‬ ‫إَزشوَبد‬
ٌ ‫كىدو‬ ٍ َُ‫إشبسح رَم ػذَذ األد‬
‫انجذء‬
‫ يُؽقخ غُش يزشخًخ‬5’
‫اردبِ انُسخ‬ ‫ يُؽقخ غُش يزشخًخ‬3’

Examples
β- ‫يىسثخ خعبة‬ 3 Exons Mutation ‫ؼفشح‬
1 2 3 ٍ‫انذو انًُده‬

‫يىسثخ رشيُى انذَب‬

24 Exons ‫سشؼبٌ انثذٌ ؼفشح‬
‫انًجُط‬

β- ٍُ‫يىسثخ يُىس‬
40 Exons
‫رعخى ػعهخ ؼفشح‬
‫انقهت انًؼزهخ‬

Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

DNA, RNA & proteins: Heredity at the molecular level:

All genetic disorders involve mutations at the cell level.
Errors / mutations occur during:
1. Gene replication ‫رعبػف‬
2. Gene transcription & Splicing ‫انُسخ وانًؼبندخ‬
3. Gene translation ‫ رشخًخ‬into proteins
Cell nucleus contains chromatin (DNA + Histones) = genetic materials
During cell division chromatin becomes visible as chromosomes
Chromosomes are the carriers of genes
Physical genes are made of DeoxyriboNucleic Acid (DNA)
DNA provides the BLUEPRI NT ‫ يُخَؽَػ‬for all proteins in the body:
Proteins influence all aspects of body structure & function
There are 23,000 structural genes:
Structural genes = that code for mRNA then proteins Mutation
Mutation: an error in one of the structural genes often leads to
genetic disorder

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Defects at the cell level can cause

Examples
DMD
Double muscle

Double muscle:
muscle: is caused by lack of the
A patient with late-stage protein Myostatin
Myostatin..
Duchenne Muscular Dystrophy,
showing severe muscle loss.

Duchenne Muscular Dystrophy (DMD): is caused by lack of Dystrophin

protein; this causes skeletal muscle cells to collapse when they contract.

Wilson Disease is caused by build up of Copper Cu++

& the liver fails to dispose it.
Mutation
Wilson Disease (MIM 277900
277900):
):-- Example
Initial symptoms:-
1. Stomachaches
2. Headaches
3. Inflamed liver (hepatitis)
Later symptoms:-
1. Slurred speech ‫رذاخم انكالو‬
2. Loss of balance
3. Altered hand writing
4. Unable to talk & walk A greenish ring around the brownish
iris is one sign of the copper build up
Treatment:-
Treatment:- of Wilson Disease.
1. Penicillinamine enables the excretion
of the excess of copper in the urine,
2. This halts the course of illness

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Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

The Cytoskeleton ٌّ‫ انهُكم انخهى‬:

Example RBC
1. The cytoskeleton gives a cell its specific
architecture
2. The major cytoskeleton components
include:-
a. Microtubules (tubulin)
b. Microfilaments (actin)
c. Intermediate filaments. (Dismins; Keratin)
3. Spherocytosis ‫ ركىس انكشَبد انسًشاء‬is a
heredity defect in the cytoskeleton of the
red blood cells. An abnormal cytoskeletal
protein, Ankyrin, lies beneath the cell
membrane & causes the red blood cells to
balloon out, blocking narrow blood
vessels in organs.

Hannah
Giant Axonal Neuropathy Sarah
‫اػزالل انؼصجىَبد انؼًالقخ‬ Sames
(HSS)
1. HSS was born March 5th 2004
2. At 2 years & 5 months of age:-
 Left arch of eye moving inward (ْ‫) زَىَ ل‬
3. At 3 years :-
 Both arches moving inward!!! Example
 Her gait (‫ ) يشُزهب‬had become awkward.
4. Pediatric Neurologist & Pediatric Geneticist:-
 Diagnosed the symptoms as:- Giant Axonal Neuropathy
(‫) اػزالل انؼصجىَبد انؼًالقخ‬
 Intermediate filaments control axon shape.
 A Gigaxonin (a key protein in neurofilaments) is not
dismantled & builds up in axons distending them to
become Giant.
 No cure no treatment !! ??? It is sad……

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Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics
Example

Cell-Cell Interactions cellular communications:-

1. In signal transduction‫ َقم اإلشبسح‬, receptors get information from
extracellular 1st messengers & trigger the release of second messengers
inside the cell. The 2 nd messengers cause a reaction within the cell.
2. Neurofibromatosis type I (NF1) ٍِّ‫ وُساوٌ نُِفٌٍِ ػَصَج‬is caused by faulty signal
transduction. Nerve cells beneath the skin inappropriately transmit a
growth factor signal, triggering cell division & a tumor forms.
NeuroFibromatosis Autosomal dominant Neurofibromatosis type I
A, A young adult with (NF1)
multiple neurofibromas of type 1 (NF1)
the trunk. A coffee-with-milk
spots can be seen in the right
upper abdomen.
B, In a second patient with
NF1, a large plexiform
neurofibroma hangs from the B
lower right back.
C, more sever case. A B C

Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

Cellular Adhesion Cellular adhesion Example

1. Cell adhesion is a precise
sequence of interactions
between cell surface proteins Selectin
that join cells.
2. In inflammation ‫ انْزِهبة‬, Cell
Adhesion Molecules (CAMs)
Integrin ‫ثشورُُبد يسزقجم‬
guide white blood cells to
‫االنزصبق‬
injury sites.
3. Leukocyte-adhesion deficiency
& cancer are disorders that can
result from abnormal cell
adhesion.

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Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

Stem Cells ; Cell Lineages ‫أسويبد‬

1. Stem cells are non-specialized cells that
retain the potential to differentiate &
enable a tissue to grow or repair itself. ‫خهُخ‬
‫خز ػُخ‬
2. A fertilized egg is Totipotent ‫شبيِمُ انىُسْغ‬,
capable of producing any cell type. ‫يُكَىٌَِخ نهذَو‬
3. Later in development, Pluripotent ُ‫يُزَؼَ ذِ د‬
‫ انقُذْسَاد‬stem cells give rise to Progenitor
‫خهُخ سهف‬
cells that are committed to a particular
pathway. Progenitor cells ‫خالَب سهف‬never
self-renew.
4. Stem cells persist in many adult tissues
& have the potential to replace injured Stem cells &
progenitor cells
or diseased tissue.

Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

Stem Cells in Health Care

Research into stem cells to replace or rejuvenate injured tissue:-
1. In drug discovery & development.
2. To observe the earliest sings of a disease.
3. Implants ٌ‫ & ؼُؼْى‬Transplants ‫ اِ صْدِساع‬for treatment.
4. Creation of iPS cells. Induced Pluripotent Stem (iPS) cells.
A. Reprogrammed motor Example
neurons from an ALS patient
B. An ALS patient who died
later
ALS=
ALS =Amyotrophic Lateral
Sclerosis ٌِّ‫رَصَ هُتٌ خَبَِجٌٍِ ظًُىس‬
Motor neurons enable a person
to move gradually fail
ALS patient
A B

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Basic cell Biology/Genome Medical

Structure & Function of Genes & Chromosomes Genetics

Case study
 In 1960 a 3 years old Michael M. lost his left
eye in an accident
 His vision in right eye was impaired by scars Michael M.
ٌ‫ َُذَة‬on the cornea
 He could see dim light
 Several cornea transplants failed
 At age 39 he received stem cells from
a donor & transplant was successful
 Researchers learned that corneal transplant
work only if the transplanted tissue includes
stem cells
 Michael retained sight‫ ثصش‬but not vision ‫ثصُشح‬
 Slowly his brain caught up with his senses &
he was able to see his family for the first time

Medical
The cell cycle ‫انذاسح انخهىَخ‬ Genetics

The cell cycle Meiosis Mitosis

2n = 4
1. Mitosis 2n = 4

2. Meiosis
3. Regulation
of cell cycle

n=2 n=2 2n = 4 2n = 4

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Medical
Homologous Chromosomes Genetics

 In diploid species, members of a pair of

chromosomes are called homologues
 They are homologous chromosomes ‫انصجغُبد انًزدبَسخ‬
 Each homologue nearly identical in size and
genetic composition
 Both carry gene for eye color but one may have
brown and the other blue
 Sex chromosomes are very different from each
other - X and Y differ in size & composition

Homologous chromosomes ‫انصجغُبد انًزدبَسخ ورىصع انًىسثبد وأنُالرهب‬

a a Alleles ‫أنُالد‬ A A

e e e e

B B b b

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The cell cycle

The cell cycle is depicted as
a circle:-
1. G1 phase, involves growth,
centrosome duplication, &
preparation for DNA
synthesis
2. S phase, a copy of the
genome is duplicated
3. G2, prepares the cell for
mitosis
4. M phase, replicated
chromosomes are
partitioned.
5. Cytokinesis divides the cell
into two cells with
identical genomes.

The cell cycle

‫خُُىو‬/ ‫رعبػف انصجغُبد‬
‫خسى يشكضٌ يزعبػف‬

Start

End

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Cell decision to divide

1. External factors ) ‫ػىايم خبسخُخ (هشيىَبد‬
2. Internal factors )‫ػىايم داخهُخ ( ثشورُُبد َقبغ انًشاقجخ‬

Checkpoint proteins ‫ثشورُُبد َقبغ انًشاقجخ‬

 Cyclins & cyclin
yclin--dependent kinase
inasess (cdks
cdks))
responsible for advancing a cell through the
phases of the cell cycle
 Amount of cyclins varies through cycle
 Kinases controlling cell cycle must bind to a cyclin
to be active

Checkpoints in the cell cycle

‫َقبغ انًشاقجخ فٍ انذاسح انخهىَخ‬

G 1 cyclin is degraded
after cell enters S phase.

cdk Mitotic cyclin

Activated G 1
cyclin/cdk cdk
1 S
complex
G1 G2

M 2
G 1 cyclin cdk Activated Mitotic
cdk
3 cyclin/cdk
complex

Mitotic cyclin is degraded as cell

progresses through mitosis.

control of cell cycle

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Medical
Stages of Mitosis Genetics

Mitosis: is the process by which the contents of the eukaryotic nucleus are
separated into two genetically identical packages.
Mitosis is divided into 4 stages:-
1. Prophase:- Chromosome condense & become short & the nuclear
envelope disintegrates and a spindle of microtubules forms.
2. Metaphase:- The chromosomes begin to move toward the mid-
plane of the spindle. Each chromosome is made of two sister
chromatids.
3. Anaphase:- as the centromeres separate and the sister chromatids,
now termed chromosomes, are pulled toward opposite poles of the
spindle.
4. Telophase:- a nuclear envelope forms around each set of
chromosomes, the spindle disappears and the chromosomes
decondense. The result is 2 nuclei, each with an identical set of
chromosomes.

The process of mitosis in an animal cell

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The process of mitosis in an animal cell

Apoptosis ‫اسزًبرخ‬ Medical

Genetics

Apoptosis ‫انًىد انًجشيح‬/‫ اسزًبرخ‬:

1. Mitosis (cell division) & Apoptosis (cell death) are
continuous processes that are both initiated by signals
in the extracellular environment.
2. The balance between cell division & death maintains
tissues in growth, development, & repair.
3. In prenatal development, coordination of these
processes sculpts ‫ رُسذ‬body form.
4. After birth, mitosis & apoptosis protect & maintain the
body.
5. Disruption of the balance between cell division & cell
death can lead to cancer or other disorders.

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Telomeres
How can a cell know how many divisions remain?
1.Telomeres
1. Telomeres function like fuses that burn down as
pieces are lost from ends every cell division.
2.Every mitosis, telomeres lose 50-200
nucleotides
3.After 50 mitosis critical length of DNA is lost
4.This signals mitosis to stop
5.Cell either enters G0 or die Syndactyly: apoptosis failed

Medical
Stages of Meiosis Genetics

 Sexual reproduction ٍ‫انزكبثش اندُس‬

requires a fertilization
‫ إخصبة‬event in which two haploid gametes unite to create
a diploid cell called a zygote
 Meiosis: is the process by which haploid cells (gametes)
are produced from a diploid cell
 Like mitosis, meiosis begins after a cell has progressed
through the G1, S, and G2 phases of the cell cycle
 Two key differences:
1. Homologous pairs ‫ رضاوج انصجغُبد انًزدبَسخ‬form a bivalent
or tetrad
2. Crossing over ‫ & انؼجىس‬Recombination ‫???انزأشُت‬

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Medical
Recombination ‫انزأشُت‬ Genetics

‫سخم‬/ٌ‫ صجغُبد اإلَسب‬:‫شكم‬

‫ فٍ انؽىس‬2n=44+XY
. Prophase-I I-ٌ‫انزًهُذ‬
ٍُُ‫الزظ رضاوج انصجغٍُُ اندُس‬
Recombination

‫انزأشُت‬

Human
chromosomes X-Y recombination
during Spermatogenesis
recombination Embryogenesis

G1 phase prior to meiosis

Homologous pair of A diploid cell
chromosomes prior to
Chromosomal replication 2n
Chromosomes replication
Meiosis I
Diploid cell with Stages of
replicated & condensed
Chromosomes 2n Meiosis
Sister chromatids

2 Haploid cells with

pairs of sister
Chromatids n n

Meiosis II

n n n n
4 Haploid cells with individual chromosomes

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2n = 6 Stages of Meiosis
Meiosis I
(a) Prophase I (b) Prometaphase I (c) Metaphase I (d) Anaphase I (e) Telophase I and cytokinesis
Bivalent Metaphase plate

n n
Centrosome Bivalent
Meiosis II Cleavage furrow
(f) Prophase II (g) Prometaphase II (h) Metaphase II (i) Anaphase II (j) Telophase II and cytokinesis

n n n

n n
n

meiosis_II[1] meiosis_I[1]
n=3

Medical
Course Work Assignments Genetics

Assessment Marks
First Test Theoretical exam 6 th week 20
Second Test Theoretical exam 12 th week 20
Activity & Participation 2½
Course Work Activity & Participation 2½ 10
Research Project Presentation 5
Final Exam 16 th week 50
Total 100
Course Work Assignments
Topic = Genetic Disorders
Type of Work:
1. Two Students Work Together
2. PowerPoint Presentation 10 min
3. Link: www.ygyh.org

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www.ygyh.org

No. Disease Name Name of Students + Time of Presentation

1 Alzheimer Disease
2 Beta-Thalassemia
3 Cystic Fibrosis
4 Down Syndrome
5 Duchene-Becker Muscular Dystrophy
6 Fragile X-Chromosome
7 Hemochromatosis
8 Hemophilia
9 Huntington Disease
10 Marfan Syndrome
11 Neurofibromatosis
12 Phynylketounuria-PKU
13 Polycystic kidney disease
14 Sickle cell anemia
15 Tay-Sachs

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Medical
Discoverer of DNA Structure Genetics

*****
ٌ‫شىفى أَب خًُس واؼسى‬
Look I am JAMES D. WATSON

## #
‫شكشاً نسسٍ االسزًبع‬

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