Genetics Single Gene Defect (AD&AR) Flashcards
What is the likely type of single gene disorder here?
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What is the likely type of single gene disorder here?
AR
Consanguinity increases risk for AR disorders
What is the likely type of single gene disorder here?
[…]
What is the likely type of single gene disorder here?
AD
If first case, tbh cannot tell that its AD at all.
A set of parents have average stature. They have a child with achondroplasia. What is the most likely mechanism for the child’s condition?
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A set of parents have average stature. They have a child with achondroplasia. What is the most likely mechanism for the child’s condition?
Can be spontaneous mutation or germline mosaicism
Cuz achondroplasia is AD! Thats y important to memorize which genetic condition is which type of inheritance cuz exam questions wont tell u!
An autosomal recessive (AR) condition is defined as one in which the condition is clinically manifested in the homozygote/compound heterozygote but not in the heterozygote.
What are some 5 AR disorders we need to know?
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An autosomal recessive (AR) condition is defined as one in which the condition is clinically manifested in the homozygote/compound heterozygote but not in the heterozygote.
What are some 5 AR disorders we need to know?
- Beta Thalassaemia (SE Asia)
- Cystic Fibrosis (Northern Europe)
- Phenylketonuria (Northern Europe)
- SCID
- Sickle cell anaemia
“Beta Cats Pheel Severely Sick”
In an AD condition, it is important to determine the origin of the pathogenic variant as the risk of recurrence is dependant on the origin of the pathogenic variant.
When a couple has a child with an AD condition, what are the 4 possible scenarios?
[…]
In an AD condition, it is important to determine the origin of the pathogenic variant as the risk of recurrence is dependant on the origin of the pathogenic variant.
When a couple has a child with an AD condition, what are the 4 possible scenarios?
- both parent heterozygous for pathogenic variant, one of them pass to child
- one parent has pathogenic variant in all cells
- one parent has germline mosaicism
- both parent no pathogenic variant, child represents new mutation
Osteogenesis Imperfecta is an example of […] in AD diseases
Osteogenesis Imperfecta is an example of Dominant Negative Effect in AD diseases
Having an abnormal protein is worse than having no protein in OI because the abnormal protein in dominant negative effect screws up the function of the normal protein.
Single gene disorders follow clear patterns of inheritance and can be associated with an increased risk of recurrance in an affected family
What are the 5 types of single gene disorders?
[…]
Single gene disorders follow clear patterns of inheritance and can be associated with an increased risk of recurrance in an affected family
What are the 5 types of single gene disorders?
AR, AD, XLR, XLD, Y-linked
The types of variability in the phenotype in AD disorders are listed as followed. What does each type mean?
- Incomplete/reduced penetrance
[…] - Sex dependent/independent penetrance
[…] - Age related penetrance
[…] - Variable expressivity
[…]
The types of variability in the phenotype in AD disorders are listed as followed. What does each type mean?
- Incomplete/reduced penetrance
- some individuals with pathogenic variant fail to manifest any sign or symptom of the condition
- e.g amongst 100 females who have pathogenic BRCA1 variant, only 60 females develop breast cancer during their life time - Sex dependent/independent penetrance
- **one gender associated with higher risk of having any sign or symptom of the disease **
- e.g amongst 100 males who have pathogenic BRCA1 variant, almost none develop breast cancer during the life time - Age related penetrance
- ***features of disease comes on with age
- e.g Most persons with NF-1 are born without any features of the disease but all will develop significant features by 20 years of age *
*- Means delay in diagnosis, needing to guard against false reassurance and risks of mis-diagnosis
* - Variable expressivity
- *Individuals with same disease have differing severity *
- e.g individuals with NF-1 have different number of spots, lumps and frecklings
Note that pt with pathogenic variant can pass to next generation REGARDLESS of the signs and symptoms being shown or not
Penetrance is defined as the fraction of individuals who have genetype known to cause a disease AND who have any signs or symptoms of the disease
Possible mechanisms for penetrance include genetic heterogeneity, gene-gene interactions, gene-environment interactions
What are some characteristics of AD disorders?
- Phenotype appears in […] generation except (new mutation, germline mosaicism, non-penetrance)
- Both sexes are […] affected (same as AR)
- Risk of recurrence for parents is […]% in each pregnancy except (new mutation, germline mosaicism, etc)
What are some characteristics of AD disorders?
- Phenotype appears in every generation except (new mutation, germline mosaicism, non-penetrance)
- Both sexes are equally affected (same as AR)
- Risk of recurrence for parents is 50% in each pregnancy except (new mutation, germline mosaicism, etc)
Affected individuals for AD are almost always heterozygotes
What are some characteristics of AR disorders?
- Parents of the affected are asymptomatic carriers and are usually phenotypically […]
- Both sexes are […] affected
- Risk of recurrence for parents is […]% in each pregnancy
What are some characteristics of AR disorders?
- Parents of the affected are asymptomatic carriers and are usually phenotypically normal
- Both sexes are equally affected
- Risk of recurrence for parents is 25% in each pregnancy
What are some examples of AD disorders?
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What are some examples of AD disorders?
- Familial Hypercholesterolemia (FH)
- Familial Adenomatous Polyposis
- Achondroplasia
- Neurofibromatosis Type 1
- Osteogenesis Imperfecta
“Familiar Families Amuse Nerdy Officers”
More:
- Tuberous Sclerosis
- AD polycystic kidney disease
- Huntington’s chorea
- Myotonic dystrophy
What are the special considerations in AD disorders (unlike AR disorders)?
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What are the special considerations in AD disorders (unlike AR disorders)?
- Variability in the phenotype
- Homozygosity for AD disorders
- New mutation
- Germline Mosaicism
What are the ways that a pathogenic variant can result in an AD disease?
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What are the ways that a pathogenic variant can result in an AD disease?
- Haploinsufficiency (FH)
- Gain of function (achondroplasia)
- Dominant Negative Effect **(Osteogenesis Imperfecta) **
Haploinsufficiency lowkey = 1/2 loss of function? HAHHAHA
Dominant negative effect = pathogenic variant produces abnormal product that interferes with normal product. Hence named “dominant negative”
What does homozygosity in AD conditions mean?
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What does homozygosity in AD conditions mean?
Affected homozygotes are often more severely affected and/or lethal
What is germline mosaicism? (IMPT)
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What is germline mosaicism? (IMPT)
**occurs when a person has at least 2 genitically different cell populations **
- e.g some cells are normal but some cells have pathogenic variant
