Monogenic inheritance Flashcards
Definition of monogenic inheritance?
Inheritance of characteristic through single gene
What are Mendel’s 3 laws of inheritance?
- Law of dominance- principle of dominant & recessive
- Law of segregation- only 1 allele for each train is passed to offspring- segregation of alleles occur when gametes formed
- Law of independent assortment- traits are inherited separately from each other- seed shape has no impact on seed colour
What are the 6 major modes of monogenic inheritance?
Autosomal dominant inheritance
autosomal recessive inheritance
x-linked dominant inheritance
x-linked recessive inheritance
y- linked inheritance
mitochondrial inheritance
Autosomal dominant- When is offspring affected by disease? Chnace that child inherits disease?
Affected offspring occur when 1 parent has the affected heterozygote, Aa.
- Affected parent can either pass on the disease allele, A or the normal allele, a.
50% chance of being affected (heterozygote) & 50% of being unaffected (homozygote)
*look at punnet square on notes
Autosomal dominant- what pattern does it show on pedigree diagram?
No skipping of generations
Vertical transmission
2 sexes affected equally
Father-to-son transmission - rules out condition being X-linked.
One parent must have the disease for it to be passed on.
Autosomal dominant- examples of conditions?
- Huntington’s disease
- Marfan Syndrome
- Postaxial Polydactyl
- Autosomal Dominant … Ataxias
Autosomal dominant- recurrence rate?
50%
recurrence rate- probability of future child being affected by disease
Autosomal recessive: when is offspring affected by disease? What is chance individual gets disease?
Parents are usually both heterozygous carriers, Aa.
25%chance if both parents are carriers.
*look at punnet square on notes
Autosomal recessive: pattern of inheritance shown on pedigree diagram?
Not seen generation-to-generation
Horizontal transmission - seen in siblings
Sexes affected equally
Consanguinity (related people) is present more often
*look at pedigree diagram on notes
Autosomal recessive- examples of conditions?
- Cystic fibrosis
- Sickle cell anaemia
- Albinism
Autosomal recessive- recurrence rate?
- 25% for Aa & Aa (2 carriers)
- 50% for Aa & aa (1 carrier & 1 with disease)
X-linked dominant inheritance- when is offspring affected? Impact of Affected mother & affected father?
If female inherits 1 normal copy & 1 faulty copy of gene- will be enough to cause the condition.
If male inherits faulty X chromosome- causes the condition.
- An affected male - 100% daughters will be affected & all sons will be unaffected
- Affected female- 50% chance of having affected children, both males & females
Daughters may have disease more mildly than sons because second X chromosome may reduce the impact of the diseased X gene.
- draw punnet squares to workout %
X-linked dominant inheritance: what pattern does it show on pedigree diagram?
Vertical transmission
Affected individuals predominantly female- as men can only pass affected X allele to daughters
Father to son transmission impossible
*Look at pedigree diagram on notes
X-linked dominant inheritance: examples of conditions?
Fragile X syndrome
Rett syndrome
X-linked recessive inheritance: Which offspring affected? What is chance they will get disease? What if mother & father affected (separately)?
Usually only affects males
Female carrier- will pass on either faulty or normal x chromosome- so 50% chance of developing disease & 50% chance of being healthy for sons, & 50% chance of inheriting faulty gene & becoming carrier & 50% chance of being health for daughters.
Affected male- son will never inherit faulty gene as men always pass Y chromosome to sons. Daughter will inherit faulty gene as men only have 1 X chromosome- all daughter become carriers
X-linked recessive: pattern of inheritance in pedigree diagram?
Inheritance skips generation
only evident in males
Affected boys may also have affected maternal uncles
*look at pedigree on notes
X-linked recessive: Examples of conditions?
Haemophilia
Red-green colour blindness
Duchenne muscular dystrophy
Y-linked inheritance: what is it? pattern of inheritance? Examples of conditions?
Altered gene located on Y chromosome
Only affects males
passed from father to son
Conditions: Y chromosome infertility, Swyer syndrome
*look at pedigree diagram
Mitochondrial inheritance: pattern of inheritance? Pattern on pedigree diagram? Examples of conditions?
Only egg cells contribute mitochondria to developing embyro- so only females can pass mitochondrial variants to offspring
Appears in every gen & affects both males & females
Males do not pass condition onto osspring
Conditions: Leigh’s syndrome, LHON, MELAS
*Look at pedigree on notes
What is Huntington Disease?
Progressive brain disorder
Causes uncontrolled movements, emotional problems & loss of thinking
Irritability, depression & involuntary movements
What causes Huntington disease?
Mutation in HTT gene
HTT provides instruction to make Huntington protein- important for neurons in brain
CAG trinucleotide (DNA segment) repeated 36-120 times, rather than usual 10-35 times
- segments are then cut into smaller toxic fragments that accumulate in neurons & lead to death
What is cystic fibrosis?
Disease of mucus & sweat glands
affects lungs, pancreas, liver &intestines
causes mucus to become thick & sticky- makes it easier for bacteria to grow- leads to repeated lung infections
What causes cystic fibrosis?
Mutations in CFTR gener
Gene provides instructions for making channel proteins that transport chlorine ions out of cells (chloride helps control water in cells)
This is necessary for thin, freely flowing mucus
What is haemophilia?
Bleeding disorder- slows the blood clotting process
people experience prolonged bleeding after trauma
What causes Haemophilia?
Changes in F8 gene for Haemophilia A
Changes in F9 gene for Haemophilia B
Genes provide instructions for making coagulation factor VIII & IX
Altered protein cannot effectively participate in blood clotting cascade= continuous bleeding
What is sickle cell disease?
Group of disorders that affect haemoglobin
People have Haemoglobin S- distorted sickle shape
Sign of disease= low level or red blood cells- anaemia
What are genetic causes of Sickle cell?
Mutation in HBB gene
HBB provides instructions for making beta globulin chains of Hb
What is the pathology of sickle cell disease? How does it cause symptoms?
Sickle red blood cells breakdown prematurely- leads to anaemia
Anaemia causes fatigue, shortness of breath, delayed growth in children
Pain caused by sickle shaped RBCCs (which are inflexible) getting stuck in small blood vessels- deprives tissues & organs of blood= organ damage
What causes Colour blindness?
Mutation in OPN1LW, OPN1MW & OPN1SW genes
X-linked recessive
