Palestine Polytechnic

University

1 Medicine College & Health

Science
Medical Genetics Introduction
DR : Omar Mohammad
 2 What’s a ___?
 Genetics : Is the branch of biology that deals
with heredity and variation in all living
organisms
 The subfields of genetics :
 Human genetics,
 Animal genetics,
 Plant genetics
 Medical genetics
 Medical Genetics
3
 Is the science or study of biological
variation as it pertains to health and
disease
 Medical genetics involves any application of
genetics to medical practice.
1. It thus includes studies of he inheritance
of diseases in families,
2. mapping of disease genes to specific
locations on chromosomes,
3. analyses of the molecular mechanisms
through which genes cause disease, and
4
 As a result of rapid progress in
molecular genetics,
 DNA-based diagnosis is available for
several thousand inherited conditions,
and
 gene therapy the insertion of normal
genes into patients in order to correct
genetic disease
 Why Is A Knowledge Of Medical
5 Genetics Important For Today’s
Health-care
 Genetic diseases make up Practitioner?
a large percentage of the
total disease burden in pediatric and adult
populations .
 modern medicine is placing increasing emphasis on
prevention.
 Because genetics provides a basis for understanding
the fundamental biological makeup of the organism,
it naturally leads to a better understanding of the
disease process.
 In some cases, this knowledge can lead to prevention
of the disorder.
 It also leads to more effective disease treatment.
( Prevention and effective treatment are among the
highest goals of medicine. )
6 A Partial List of Some
Important Genetic Diseases
Chromosome Abnormalities
 Down syndrome 1/700 to 1/1000
 Klinefelter syndrome 1/1000 males
 Trisomy 13 1/10,000
 Trisomy 18 1/6000
 Turner syndrome 1/2500 to
1/10,000 females
 7

Single-Gene Disorders
 Adenomatous polyposis coli 1/6000
 Adult polycystic kidney disease 1/1000
 α1-Antitrypsin deficiency 1/2500 to
1/10,000
 Cystic fibrosis 1/2000 to
1/4000
 Duchenne muscular dystrophy 1/3500 males
 Familial hypercholesterolemia 1/500
 Fragile X syndrome 1/4000 males;

1/8000 females
 Hemochromatosis (hereditary) 1/300 whites are
homozygotes; approximately 1/1000
to 1/2000 are affected
8  Hemophilia A 1/5000 to 1/10,000
males
 Hereditary nonpolyposis colorectal cancer Up to
1/200
 Marfan syndrome 1/10,000 to 1/20,000
 Neurofibromatosis type 1 1/3000 to 1/5000
 Osteogenesis imperfecta 1/5000 to 1/10,000
 Phenylketonuria 1/10,000 to 1/15,000
 Retinoblastoma 1/20,000
 Sickle cell disease 1/400 to 1/600
 Thalassemia 1/50 to 1/100 (South
Asian and circum-
Mediterranean
populations)
9 Multifactorial Disorders
 Congenital Malformations
 Cleft lip with or without cleft palate

1/500 to 1/1000
 Club foot (talipes equinovarus)
1/1000
 Congenital heart defects 1/200 to
1/500
 Neural tube defects (spina bifida,
anencephaly) 1/200 to
1/1000
 Pyloric stenosis 1/300
10
 Adult Diseases
 Alcoholism 1/10 to 1/20
 Alzheimer disease 1/10 (Americans
older
than 65 years)
 Bipolar disorder 1/100 to 1/200
 Cancer (all types) 1/3
 Diabetes (types 1 and 2) 1/10
 Heart disease or stroke 1/3 to 1/5
 Schizophrenia 1/100
11

Mitochondrial Diseases
 Kaerns-Sayre syndrome
 Leber hereditary optic neuropathy
(LHON)
 Mitochondrial encephalopathy, lactic
acidosis, andstroke-like episodes
(MELAS)
 Myoclonic epilepsy and ragged red
fiber disease (MERRF)
 Genetics – history and key
1860s concepts…
Mendel’s work
1940s
Barbara
McClintock
on peas allows describes 1977 Phillip
the conclusion mobile Sharp and
that traits are genetic Richard Roberts
inherited elements find that protein-
through in maize coding genes are
discrete units carried in
passed from 1944 segments
one Oswald
generation to Avery
1870s
the nextFriedrich shows in
Miescher
bacteria
describes nucleic
that
acids
1909 The word nucleic
2001 initial
‘gene’ coined by acids are
results from
12 Danish botanist the
the Human
1953 James
‘transform
Wilhelm Johannsen Watson and Genome
1910 Thomas ing
Morgan’s work Francis Crick Project
principle’
on fruitflies publish the double published
1958 Crick
demonstrates helix model for
proposes the
that genes lie DNA’s chemical
‘central dogma’
on structure
for biological
chromosomes information flow:
 Medical Genetics:
13
1950s to the present
 DNA Genetics
• 1953 - Watson and Crick’s Double
Helix
• 1992 –2003 Human Genome Project
• 2003 -> the future of medical dx & tx
 Prenatal Genetics
 1970s - Prenatal Ultrasound & Amniocentesis
 Inheritance of Genetically Complex Disorders
 Non-Mendelian Genetics
• Genomic Imprinting
• Triple Nucleotide Repeats
• Mitochondrial Inheritance
 1990s - Neuropsychiatric Disorders, Diabetes,
Cardiovascular
 Interaction of genes with environmental
 Genetic Information

 Gene – basic unit of genetic

information. Genes determine
the inherited characters.

 Genome – the collection of

genetic information.

 Chromosomes – storage units

of genes.

 DNA - is a nucleic acid that

contains the genetic
instructions specifying the
biological development of all
cellular forms of life 14
 Chromosome Logical
Structure
 Locus – location of a
gene/marker on the chromosome.

 Allele – one variant form of a

gene/marker at a particular locus.

Locus1
Possible Alleles:
A1,A2

Locus2
Possible Alleles:
B1,B2,B3
15
 Human Genome
Most human cells
contain 46
chromosomes:

 2 sex
chromosomes
(X,Y):
XY – in males.
XX – in females.

 22 pairs of
chromosomes named
autosomes.
16
17
Glossary & Definitions
 Phenotype - the physical description of the
character in an individual organism
i.e a green eyes
 Genotype - the genetic constitution of the
organism
 Mutation - a change in the genetic material,
usually rare and pathological

 Polymorphism - a change in the genetic

material, usually common and not
pathological
18 The colure of eyes, the
colour of skin is heredity
19 The colour and structure of
our hair is also heredity
 What we’ve learned from our genome
20
 There are a relatively small number of human
genes, less than 30,000, but they have a
complex architecture that we are only
beginning to understand and appreciate.
 We know where 85% of genes are in the
sequence.
We don’t know where the other 15% are
because we haven’t seen them “on” (they
may only be expressed during fetal
development).
We only know what about 20% of our genes
do so far.
 So it is relatively easy to locate genes in
the genome, but it is hard to figure out
what they do.
21
Human genome content

 1-2 % codes for protein products

 24% important for translation
 75% “junk”
 Repetitive elements
Satellites (regular, mini-, micro-)
Transposons
Retrotransposons
Parasites
22 Types Of Genetic
Diseases
 Humans are estimated to have approximately
20,000 to 25,000 genes. Alterations in these
genes, or in combinations of them, can
produce genetic disorders.
 These disorders are classified into several
major groups:
1. Chromosome disorders, in which entire
chromosomes (or large segments of them)
are missing, duplicated, or otherwise altered.
 These disorders include diseases such as
Down syndrome and Turner syndrome.
 2. Disorders in which single genes are altered;
23
these are often termed mendelian conditions,
or single-gene disorders. Well-known
examples include cystic fibrosis, sickle cell
disease, and hemophilia.
3. Multifactorial disorders, which result from a
combination of multiple genetic and
environmental causes. Many birth defects,
such as cleft lip and cleft palate, as well as
many adult disorders, including heart disease
and diabetes, belong in this category.
4. Mitochondrial disorders, a relatively small
number of diseases caused by alterations in
the small cytoplasmic mitochondrial
chromosome
 The Clinical Impact Of
24
Genetic Disease
 Less than a century ago, diseases of largely non-
genetic causation (i.e., those caused by
malnutrition, unsanitary conditions, and pathogens)
accounted for the great majority of deaths in
children.
 During the 20th century, however, public health
vastly improved . As a result, genetic diseases have
come to account for an ever-increasing percentage
of deaths among children in developed countries.
 For example, the percentage of pediatric deaths
due to genetic causes in various hospitals in the
United Kingdom increased from 16.5% in 1914 to
50% in 1976 .
25

 In addition to contributing to a large

fraction of childhood deaths, genetic
diseases also account for a large share of
admissions to pediatric hospitals.
  Another way to assess the importance of
26 genetic diseases is to ask, “What fraction of
persons in the population will be found to
have a genetic disorder?” A variety of factors
can influence the answer to this question.
 For example, some diseases are found more
frequently in certain ethnic groups. Cystic
fibrosis is especially common among those of
European heritage , where as sickle cell
disease is especially common among those of
African descent.
 Some diseases are more common in older
persons. For example, colon cancer, breast
cancer, and Alzheimer disease are caused by
 Some Facts
27  In human beings, 99.9% bases are same

 Remaining 0.1% makes a person unique

 Different attributes / characteristics / traits
 how a person looks
 diseases he or she develops
 These variations can be:
 Harmless (change in phenotype)
 Harmful (diabetes, cancer, heart disease,
Huntington's disease, and hemophilia )
 Latent (variations found in coding and
regulatory regions, are not harmful on their
own, and the change in each gene only
becomes apparent under certain conditions
e.g. susceptibility to heart attack)
 Importance of Genetics
28
to Medicine
 ≈50% of first trimester abortion are due to
chromosomal abnormalities
 Congenital malformation: ≈2-3% of
newborns.
 2% infants are born with single gene
disorder
 More than half of childhood blindness,
deafness and mental retardation are due to
genetic disorders.
 Importance of
29
Genetics to Medicine
 Changing focus of medicine:
 Primary care physicians vs specialists
 Prevention vs treatment
 Genetic causation for both rare and
common diseases
 Human Genome Project
 Designer drugs

 Genetics as the link between basic research &

clinical observation
30
Genetic Diseases
Genetic
Diseases
Chromoso Multifactoria
Unifactorial
mal l
Numeric
AD
al
Structura
AR
l
X-
Microdeletions
linked
Mitochond
rial
 The contributions of genetic and
31
environmental
Haemophilia
factors to human Diabetes
Osteogenesis imperfecta diseases
Peptic ulcer

Duchenne Club foot

muscular Pyloric Tuberculosis
dystrophy stenosis
Dislocation of
hip
GENETIC
ENVIRONMENTAL

Spina bifida Scurvy

Phenylketonuria Ischaemic heart disease
Galactosaemia Ankylosing spondylitis

Rare Genetics simple

Common Genetics complex
Unifactorial High
Multifactorial Low recurrence
recurrence rate
rate
 32
Multifactorial – Genes or
Environment?
100% Struck by lightning
Environmental
Infection

Weight

Cancer

Diabetes
PKU –genetic basis
but the damage is
Height by
an environmental
100% agent
Genetic Sex, Down syndrome, achondroplasia