POPULATION SPECIFIC CONDITIONS Flashcards
Many genetic conditions have population-specific distributions
true
- Research opportunities
* Major relevance when offering diagnostic testing.
- Frequencies of the disease may differ between groups, and the mutational basis may be different.
- Inappropriate testing may be performed and important diagnoses may be missed.
- Different mutation-specific therapies may also be required in the future.
WHY ARE SOME CONDITIONS MORE PREVALENT IN
CERTAIN POPULATION GROUPS?
- founder effect
-The loss of genetic variation that occurs when
a new population is established by a very small
the number of individuals from a larger population.
-• New population may be
distinctively different
• Genotypically
• Phenotypically
founder effect
- New population often the very small population
- ↑ inbreeding
- ↓ genetic variation
• Rare alleles will move to one of two extremes
1. Allele is soon lost altogether
2. Allele survives and becomes more dispersed throughout the population
• ↑ frequency of recessive alleles
• ↑ number in individuals homozygous for recessive traits
EXAMPLE OF A FOUNDER POPULATION IN SA
• The Afrikaner population of SA has many features of a founder population.
• Genetic mutation frequencies in the new population
may differ significantly from those in the original
population
true
WHY ARE SOME CONDITIONS MORE PREVALENT IN
CERTAIN POPULATION GROUPS? 2
- heterozygotic advantage
-The heterozygous genotype has a higher relative
fitness than either the homozygous dominant or
homozygous recessive genotype
example= sickle cell anemia
sickle cell anemia
- Affects hemoglobin
- Causes RBC to become sickle-shaped
Signs and symptoms • Anaemia • Shortness of breath • Fatigue • Delayed growth and development • Jaundice • Painful episodes • Organ damage
Autosomal recessive inheritance
heterozygotic advantage
- Carriers (sickle cell trait) are
resistant to malaria - • Expected that the allele frequency will decrease over time if it only has a negative result.
• However, areas with malaria outbreaks carriers have a distinct advantage
3.10-20% of people in certain
parts of Africa are carriers of
SCA
- Strong heterozygotic
advantage
WHY ARE SOME CONDITIONS MORE PREVALENT IN
CERTAIN POPULATION GROUPS? 3
- Consanguinity
-Marriage or reproductive relationship
between two closely related individuals
consanguinity
• Prevalent in many Middle Eastern and Arab
cultures and societies
• Offspring may be at ↑ risk for genetic disorders
because of the expression of AR gene mutations
• CLOSER the relationship the ↑ probability
that offspring will inherit identical copies of faulty
recessive genes
• Most genetic disorders are caused by recessive mutations,
• Recessive disease mutations are much more common than dominant diseases
mutations
• “Dominant” mutations are more easily eliminated by natural selection.
Humans carry an average of one to two disease-causing mutations
true
AFRICAN POPULATION: ALBINISM
• Common among black African populations in Southern Africa
• The average carrier rate for albinism in South Africa is 1 in 30, resulting in 1 in
4000 black South Africans being born with albinism.
Genes associated is involved in producing pigment (melanin)
clinical manifestation of albinism
Clinical manifestation
Fair skin and light-colored hair
Sun exposure increases the risk of skin damage and skin cancer
Reduced pigmentation of the iris and the retina
• Visual problems
• Nystagmus
• Photophobia
CAUCASIANS: CYSTIC FIBROSIS
CF the most common life-limiting disease among people of Northern European
heritage.
- One of the most common autosomal recessive disorders.
- Occurs in all of SA’s diverse population groups
- CF is a multifaceted condition with
- wide clinical variability,
- hundreds of causative CFTR variants,
cystic fibrosis is caused by
Caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Function: regulation of movement of chloride across
the epithelial membranes in the body
The movement of water across cell membranes is dependent on the correct function of the
chloride and sodium channels. The defects in CFTR result in poor movement of water
across the epithelial cell surfaces; which causes the secretions produced by many organs of
the body to be dehydrated and sticky
• It is estimated that 1 in 2 000 Caucasian babies, 1 in 12 000 babies of
mixed ancestry and up to 1 in 32 000 black African are born with CF in
South Africa
true
ASHKENAZI JEWISH POPULATION
• Several autosomal recessive genetic disorders that are more common
in Jewish populations
• Due to population bottlenecks as well as the practice of consanguineous
marriages
• Lead to a decrease in genetic diversity
• Higher likelihood that two parents carrying the same mutation will have a child who will then
have both mutations
ASHKENAZI JEWISH: TAY-SACHS DISEASE
- Rare autosomal recessive condition
- Progressively destroys nerve cells in the brain and spinal cord
- typically appear normal until the age of 3-6 months
- Development slows and muscles weaken
- With disease progression:
- Seizures
- Vision and hearing loss
- Intellectual disability
- Paralysis
- Usually only survive into early childhood
Several diseases with an unusually high frequency in Afrikaners have
been suggested to be the result of founder effects:
Sclerosteosis
sclerosteosis
- Autosomal recessive disorder characterized by bone overgrowth.
- Clinical features
- Syndactyly
- Facial distortion
- Tall stature
- Recurrent facial palsies
- Increased intracranial pressure
- Hearing loss
INDIAN: THALASSAEMIA
• Inherited blood disorder characterized by fewer red blood cells (RBC) in the body than
normal and less hemoglobin in RBC
• Symptoms include:
- fatigue, weakness, paleness, and slow growth.
- Mild forms may not need treatment.
- Severe forms may require blood transfusions or a donor stem-cell transplant
Thalassemia is most prevalent in populations having Mediterranean ancestry
true
MANAGEMENT AND GENETIC TESTING
1.Carrier screening
2.Prenatal Genetic Diagnosis (PGD)
3.Prenatal genetic testing
4.Predictive Testing
• Adult-onset conditions
- carrier screening
• Before a couple gets married or has children
• Important that BOTH partners are tested
• Mainly to prevent recessive conditions
- Discourage marriages between carriers
- PGD
- Individuals affected with a condition to have unaffected children
- Both parents are carriers of a condition and want to ensure an unaffected baby
- IVF and genetic testing before implantation of the embryo
- prenatal genetic testing
- Women who are already pregnant and want to test the fetus to determine if the fetus is affected or not.
- Patient would need to decide if they want to continue with the pregnancy or want to terminate the pregnancy
