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GENETICS
Prof. Dr. Mohamed Ali, M.Sc.. M.Phil., B.Ed., M.S (Sing)., Ph.D
(Sing)
Department of Clinical Biochemistry
Faculty of Medicine
University of Tabuk
Course Objectives
• Principles of Medical Genetics
• Application to Clinical Practice
• Understand Ongoing Developments
NO. LECTURES
1 Medical Genetics: An Overview (Biochemistry) Dr. Ali (male & Female)
Mendelian and Non-Mendelian Modes of Inheritance
2
Biochemistry Dr. Mohammad Tarik (male & Female)
3 Structural and Numerical Autosomal Anomalies Biochemistry Dr. Mohammad Tarik (male & Female)
4 Structural and Numerical Sex Chromosomal Anomalies (Biochemistry) Dr. Ali (male & Female)
5 Clinical Features and Molecular Diagnosis of Most Common Hereditary Diseases (Biochemistry)Dr. Ali (Mmale & Female)
6
Genetic Principles and Clinical Features of Most Common Hereditary Disorders (Hemoglobinopathies, Sickle-Cell Anemia, Thalassemia, Hemophilia, Albinism, Duchenne Muscular
7 Dystrophy, Fibrocystic Diseases) (Biochemistry)Dr. Ashraf Male & Female
8 Genetic Basis of Common Hereditary Diseases of Inborn Errors of Metabolism (Biochemistry) Dr.Ashraf(Male),Dr. Eman (Female)
13 Forensic Genetics and Molecular Basis of Application of DNA Finger-Printing to Forensic Science as New Tools to Solve Criminal Dilemmas (Biochemistry) Dr. Eman (Male & Female)
14 Basic Principles of Application of Genetic Engineering as a New Modality of Treatment of Many Congenital Disorders and Cancer (Biochemistry) Dr. Ali (male & Female)
4 Family History: Constructing and Interpreting a Family Tree from a Verbal Description (Family Medicine)
5
Diagnosis of Most Common Hereditary Diseases (Pediatrics)
6
8 Practice of the Genetic Counselling Clinic Including Principles of Genetic Counselling and Impact of Genetic Diagnosis on the Extended Family (Pediatrics)
NO. TUTORIALS
1 Molecular Principles of Blood Groups (Biochemistry)
2 Genetic Screening and Risk Assessment (Pediatrics)
NO. SELF-DIRECTED LEARNING (SDL)
diagnosis
albinism
Sickle cell anemia
What is Medical Genetics?
Imagining
Diagnosis
What is Medical Genetics?
Molecular incision enzyme
Diagnosis
Gel electrophoresis
What is Medical Genetics?
prenatal diagnosis
PKU/PAH (Phenylalanine
hydroxylase)
What is Medical Genetics?
Therapy
Consult
In the beginning,
There was
Mendel…
A Conceptual History of Medical Genetics
• gain-of-function
e.g. Gene dosage effects as in trisomy 21 [dominant];
Dominant-negative effect as in OI [dominant]
Abnormal protein properties as in HD [dominant]
• novel property
e.g. HbS [recessive]
• inappropriate expression
e.g. Oncogenes in cancer
Variations in phenotypic manifestation of
mutant alleles are due to:
• Focus is on disease
– Patient: someone who develops “disease” before
consulting a physician
Genetical View of Disease
• Disease is the result of mismatch between
integrated, but variable,homeostatic systems and
some experience(s) of an equally variable
environment.
• Incongruence may be potential (susceptibility) or
inevitable.
• Environment may be internal or external, physical or
social.
• Continuity of health and disease
Genetical View of Disease II
• Disease is an (almost) inevitable consequence
of our diversity.
• Focus is on the Individual.
• Management is directed at whichever
component is most amenable.
• Care rather than cure
• Prevention of disease
Genetical View of Disease III
• Why this disease ?
• Why this person ?
• Why now ?
46,XY karyotype
Androgen insensitivity syndrome, AIS
• Mechanism
Caused by mutations of the gene encoding
the androgen receptor.
• symptoms
A person with complete androgen
insensitivity syndrome (CAIS) has a female
external appearance, and suppressed
menstruation.
androgen insensitivity syndrome, AISXR
46,XY karyotype
retained testis
Introduction
•Mechanism
47,XXY (extra chromosome )
Klinefelter sydrome
mania ??
Introduction-Disease and Genetics
SARS
Bird Flu
H1N1 Flu
Introduction-Disease and Genetics
Down syndrome
connate rachitis
Conjoined Twins
Willie Shoemaker,
a famous horse racing jockey
(4 feet, 11 inches;
barely 100 pounds).
Genetic variations cause
inherited diseases
- Environment - Genes
Basic terminology
Locus – location of a gene/marker
on the chromosome.
Locus1
Possible Alleles: A1,A2
Locus2
Possible Alleles: B1,B2,B3
A little more basic terminology
Polymorphism:
- Variations in DNA sequence (substitutions, deletions,
insertion, etc) that are present at a frequency greater
than 1% in a population.
- Have a WEAK EFFECT or NO EFFECT at all.
- Ancient and COMMON.
Mutation:
- Variations in DNA sequence (substitutions, deletions,
etc) that are present at a frequency lower than 1% in a
population.
- Can produce a gain of function and a loss of function.
- Recent and RARE.
Some Facts
In human beings, 99.9% bases are same
Transversions
Purine to pyrimidine or pyrimidine to purine
Causes of gene mutations
Consequences of mutations
albinism
Genetic disease
tribe
Genetic disease
C. Classification of Genetic Disorders
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders
4. somatic cell genetic disorders
5. mitochondrial disorders
Genetic disease
C. Classification of Genetic Disorders
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders
4. somatic cell genetic disorders
5. mitochondrial disorders
Genetic disease
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders
4. somatic cell genetic disorders
5. mitochondrial disorders
In chromosome disorders, entire
chromosomes, or large segments of them, are
missing, duplicated, or otherwise altered.
Patau syndrome
Trisomy 13 -- the presence of an extra (third)
chromosome 13 in all of the cells.
Symptoms
• Physical characteristics
• Organ defects
• Mental retardation
physical characteristics
small eyes
rocker foot
Organ defects
• heart defects
• spinal defects
• abnormal genitalia
• gastrointestinal hernias
• Low IQ
99%do not survive gestation and are
spontaneously aborted
• NO TREATMENT
Genetic disease
C. Classification of Genetic Disorders
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders
4. somatic cell genetic disorders
5. mitochondrial disorders
Multiple genes are missing as a result of this
deletion, and each may contribute to the
symptoms of the disorder. One of the deleted
genes known to be involved is TERT
(telomerase reverse transcriptase). This gene
is important during cell division because it
helps to keep the tips of chromosomes
(telomeres) in tact.
Genetic disease
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders
4. somatic cell genetic disorders
5. mitochondrial disorders
Genetic disease
Somatic cell genetic diseases:
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders
4. somatic cell genetic disorders
5. mitochondrial disorders
Genetic disease
Mitochondrial genetic diseases: