Assignment of Medical

Genetics.

Group 3
Mohamed Hassan
Yahye Hassan
Hassan Omar
Hassan Hussein
Bashir Mohamed
 Cardiovascular Disorders:

Heart disease
Definition_ refers to any condition affecting the heart
which leading cause of death world wide.
Prevelence
 It accounts for approximately 25% of all deaths in
the United States.
 Causes of Heart disease:

The most common underlying cause of heart disease is

coronary artery disease (CAD), which is caused by
atherosclerosis
(a narrowing of the coronary arteries resulting from the
formation of lipid-laden lesions). This narrowing
impedes blood flow to the heart and can eventually
result in a myocardial infarction (death of heart tissue
caused by an inadequate supply of oxygen).
When atherosclerosis occurs in arteries that supply
blood to the brain, a stroke can result.
 Risk Factors for CAD:
Invironment:
 Obesity
 Cigarette Smoking
 Hypertension
 Elevated cholesterol level
 Positive Family History a person with a positive
family history is at least twice as likely to suffer from
CAD than is a person with no family history.
 Generally, these studies also show that the risk is
higher if there are more affected relatives, if the
affected relative is female (the lesscommonly affected
sex) rather than male, and if the age of onset in the
affected relative is early (before 55 years of age).
Gene Factors:

gene that encodesthe low-density lipoprotein

(LDL) receptor.
Mutations in the gene encoding
apolipoprotein B, which are seen in about 1 in
1000 persons, are another genetic cause of
elevated LDL cholesterol.
 Cardiomyopathy:
 An abnormality of the heart muscle that leads to
inadequate cardiac function.
Prevelence
 Cardiomyopathy is a common cause of heart
failure, resulting in approximately 10,000 deaths
annually in the United States.
 Nearly 100 different genes have been linked to
cardiomyopathy.
 Hypertrophic cardiomyopathy, one major form of
the disease, is characterized by thickening
(hypertrophy) of portions of the left ventricle and
is seen in as many as 1 in 500 adults.
 Gene Factors:
 The most commonly mutated genes are
those that encode the β-myosin heavy chain
(35% of familial cases), myosin-binding
protein C (20% of cases), and troponin T
(15% of cases).
 Stroke:
 Definition:
Stroke which refers to brain damage caused by a
sudden and sustained loss of blood flow to the brain,
can result from arterial obstruction (ischemic stroke,
which accounts for 80% of stroke cases) or breakage
(hemorrhagic stroke).
Prevelence:
 This disease is the fourth leading cause of
mortality in the United States, accounting for
approximately 140,000 deaths per year.
 As with heart disease, strokes cluster in families:
One’s risk of having a stroke increases by two-
to threefold if a parent has had a stroke.
 Causes
 Gene Factors:
Stroke can be caused by any of more than a dozen
singlegene disorders, including sickle cell disease
(see Chapter 3), MELAS (mitochondrial myopathy,
encephalopathy, lactic acidosis, and stroke, a
mitochondrial disordeand caused by mutations in the
NOTCH3 gene). Because blood clots are a common
cause of stroke,r discussed in Chapter 5), and
cerebral autosomal dominant arteriopathy
withsubcorticalinfarcts andleukoencephalopathy
(CADASIL, a condition characterized by recurrent
strokes and dementiaand caused by mutations in
the NOTCH3 gene). Because blood clots are a
common cause of stroke,
 Inherited deficiencies of protein C and protein S,
both of which are coagulation inhibitors, are
associated with an increased risk of stroke,
especially in children.
 A specific mutation in clotting factor V, the
factor V Leiden allele, causes resistance to
activated protein C and thus produces an
increased susceptibility to clotting.
Environment factors:
In addition to family history and specific genes,
several factors are known to increase the risk of
stroke. These include hypertension, obesity,
atherosclerosis, diabetes, and smoking.
 Hypertension:

 Hypertension. Systemic hypertension is a key

risk factor for heart disease, stroke, and kidney
disease.
 Prevelence:
It is estimated that hypertension is responsible for
approximately half of all cardiovascular
mortality. Studies of blood pressure correlations
within families yield heritability estimates of
approximately 30% to 50% for both systolic and
diastolic blood pressure.
 Causes:
 Environment factors:
The most important environmental risk factors for
hypertension are:
 increased sodium intake,
 decreased physical activity,
 psychosocial stress,
 obesity (as discussed later, the latter factor is
itself influenced both by genes and environment).
 Blood pressure regulation is a highly complex
process that is influenced by many physiological
systems, including various aspects of
 kidney function,
 cellular ion transport,
 vascular tone,
 heart function.
Because of this complexity, much research is now
focused on specific components that might influence
blood pressure variation, such as the
renin– angiotensin system
RAAS System
Gene Factors:
 Maturity-onset diabetes of the young. MODY,

Which accounts for 1% to 5% of all diabetes cases,

typically occurs before 25 years of age and follows an
autosomal dominant mode of inheritance. In contrast to
type 2 diabetes,
it is not associated with obesity.
 Causes By Gene only.
 Studies of MODY pedigrees have shown that about
50% of cases are caused by mutations in the gene
that encodes glucokinase,
 a rate-limiting enzyme in the conversion of glucose to
glucose-6-phosphate in the pancrease.
○ Another 40% of MODY cases are caused by mutations
in any of five genes that encode transcription factors
involved in pancreatic development or insulin
regulation
 hepatocyte nuclear factor-1α (HNF1α),
 hepatocyte nuclear factor-1β (HNF1β),
 hepatocyte nuclear factor-4α (HNF4α),
 insulin promoter factor-1 (IPF1)
 neurogenic differentiation 1 (NEUROD1).

Mutations in these genes, all of which are expressed in

pancreatic beta cells, lead to beta cell abnormalities and
thus to diabetes
 Alcoholism
 At some point in their lives, alcoholism
(alcohol dependence) is diagnosed in
approximately 10% of men and 3% to 5%
of women in the United States.
 Prevelence:
A More than 100 studies have shown that this
disease clusters in families: the risk of
developing alcoholism among persons with
one affected parent is three to five times
higher than for those with unaffected parents.
 Most twin studies have yielded concordance rates
for DZ twins of less than 30% and for MZ twins in
excess of 60%, with an estimated heritability of
approximately 50%.
 Adoption studies have shown that the offspring of
an alcoholic parent, even when raised by
nonalcoholic parents, have a fourfold increased
risk of developing the disorder.
 To control for possible prenatal effects from an
alcoholic mother.
 some studies have included the offspring of
alcoholic fathers only.
 Types of Alcoholism
 Alcohol dependence can be divided into different
subtypes, and some researchers distinguish two major
types of alcoholism
Type I is characterized by a later age of onset
 (after 25 years of age), occurrence in both males and females,
 and greater psychological dependency on alcohol.
 Type I alcoholics are more likely to be introverted, solitary drinkers.
 This form of alcoholism is less likely to cluster in families
 (one study yielded a heritability estimate of 0.21), has a lesssevere
course, and is more easily treated
 Type II
 Type II alcoholism is seen predominantly in males,
typically occurs before 25 years of age, and tends to
involve persons who are extroverted and thrill-
seeking. This form is more difficult to treat
successfully and tends to cluster more strongly in
families, with heritability estimates ranging from 0.55
to more than 0.80. It has long been known that an
individual’s physiological response to alcohol can be
influenced by variation in the key
 Enzymes responsible for alcohol
metabolism

 alcohol dehydrogenase (ADH), which converts ethanol to

acetaldehyde, and aldehyde dehydrogenase (ALDH), which converts
acetaldehyde to acetate. In particular, an allele of the ALDH2 gene
(ALDH2*2) results in excessive accumulation of acetaldehyde and
thus in facial flushing, nausea, palpitations, and lightheadedness.
Because of these unpleasant effects,
 persons who have the ALDH2*2 allele are much less likely to
become alcoholics. This protective allele is common in some East
Asian populations, with a frequency of approximately 40%, but is rare
in most other populations.
 Gene Causes

 One of the most consistent findings is that variants in genes that

encode components of gamma-aminobutyric acid (GABA)
receptors are associated with addiction to alcohol. This finding is
biologically plausible, because the GABA neurotransmitter system
inhibits excitatory signals in neurons, exerting a calming effect.
Alcohol has been shown to increase GABA release, and allelic
variation in GABA receptor genes might modulate this effect.
 It should be underscored that we refer to genes that might increase one’s
susceptibility to alcoholism
 . This is obviously a disease that requires an
environmental component, regardless of one’s genetic
constitution.,
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Mahadsanidiin