Transcript Clinical genetics Lect 1

Imad Fadl-Elmula
Department of Pathology
Faculty of Medicine
Al Neelain University
Definition
Study of the genes
 Medical genetics
 Clinical genetics
40.000
History
Charles Darwin
• On the evolution of species
Evolution Theory
Darwin
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Hybridization Experiments
• Basic Laws of Heredity and Law of
Independent Assortment.
• Findings rediscovered in1900.
Gregor Mendel (1822-1884)
• Augustinian monk in Fadl-Elmula
Czechoslovakia.
• Attended University of Vienna
The somatic mutation theory of cancer
Theodor Boveri (1862-1915)
Acquired genetic changes are
the main causes of malignant
transformation of target cells.
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Rise of Modern Genetics
Discovery of Chromosomes
• Walter Flemming in 1882. Salamander larva
Thomas Hunt Morgan 1910
• Fruit fly experiments in 1910. Trait are
sex linked and reside on chromosome.
• Realization that chromosomes are
blueprints of life.
Chromosomes
(?) , XX
Painter (1921)
(?) , XY
Watson and Crick
Discovered double helix structure of DNA in 1953
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46,XY
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46,XX
(Tjio & Levan, 1956)
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Mutations
Altered gene
Altered Protein
Altered function
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High incidence
2-5% of all liveborn.
30% of pediatric addmision.
Incurable and often severe
.........prevention ....Genetic counsleing
Clinical services
1. Accurate diagnosis
2. The risk of devoloping and transmision
prognosis
3. Treatment (genetherapy)
The scope of genetics
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The human genome has been sequenced!
Approximately 35,000 genes, most of which encode a
9
protein, in a haploid genome of 3 X 10 base pairs
Only about 1.5 % of the DNA actually encodes functional
genes
All living organisms are remarkably similar at the genetic
level
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Same genetic code.
About 50 % of genes comparable between us and plants.
All nucleated somatic cells have a complete set of genes.
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Only a small fraction of genes are active in a single cell
Enables cloning.
Prevalence of genetic disease
Type of genetic disease
Prevalence per 1000
Single gene
Autosomal dominant
Autosomal recessive
X linked recessive
2-10
2
1-2
Chromosomal changes
Disease with genetic base
6-7
7-10
Congenital malformations
Total
20
38-51
Genetic disease
1. Single gene (Mendelelian-4000)
2. Somatic Mutation (cancer)
3. Chromosomal (conostitusion)
4. Multifactorial (Diabetis, IHD)
Specialized laboratory
1. Cytogenetics
2. Molecular cytogenetics
3. Biochemical genetic
4. Molecular genetic
Clinical applications
Diagnostic
 Diagnostic.
Preventative
 Preventative.
☻Carrier detection
☻Population screening
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Preclinical diagnosis
Genetic monitoring
Therapeutic.
Therapeutic
Consultations and management
 Clinical geneticist.
 Developmental pediatrician.
 Cardiologist.
 Ophthalmologist.
 Neurosurgeon.
 Orthopedic specialist.
 Psychiatrist.
 Physical and occupational therapist.
 Speech-language pathologist.
 Audiologist.
Is it all what we see ?
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LOOK FROM ANOTHER ANGLE!
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E
E
E
E
E
Earth
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Sudan Country
North
Kordofan
Cell
Chromosome
Region Chromosome segment
Cities
Region
genes
S. Nucleotide
Clinical applications
Diagnostic
 Diagnostic.
Preventative
 Preventative.
☻Carrier detection.
☻Population screening.
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Preclinical diagnosis.
diagnosis
Genetic monitoring.
monitoring
Therapeutic.
Therapeutic
The genetic profiles of a disease can be
assessed at different level of resolution
Array
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CML (Bcr/Abl) (Rowley, 1973)
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FISH of BCR-ABL
Green: BCR
Red: ABL
BCR-ABL Gel
Pt 1
Pt 2
K562
Pt 1
ABL
BCR-ABL
10-4
BCR-ABL
Pt 2
K562
ABL
Prevention
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Genetic counseling
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Follow up
Evaluation of bone marrow transplants (BMT)
A girl transplanted with BM cells from her brother
interphase FISH
RELAPSE
Y chromosome
X chromosome
PROGNOSIS
AML and ALL
11q23-aberrations
Probes:
wcp10
wcp11
11
10
der(11)inv(11)(q13q23)del(11)(q13)
del(10)(p11)
11
der(14)t(11;14)(q13;q32)t(10;11)(?;q23)
14
11q13
11q23
742f9 (MLL)
11
14
VERY POOR in general
wcp11
Mitochondrial DNA polymorphisms track human
migrations
(Wallace Sci. Amer. 277:40)
"Every scientist, physician, or
paramedical who practices in the 21st
century must have an in-depth
knowledge of the principles of clinical
genetics and their application to a wide
variety of clinical conditions. Each
Health School is demanded to
incorporate genetics teaching into its
curriculum"
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