Single Gene Defects Flashcards
(38 cards)
What inheritance pattern does this family tree represent?
Autosomal dominant inheritance
What inheritance pattern does this family tree represent?
Autosomal recessive inheritance
What inheritance pattern does this family tree represent?
Autosomal recessive inheritance with consanguinity
What inheritance pattern does this family tree represent?
X-linked recessive inheritance
What inheritance pattern does this family tree represent?
Mitochondrial inheritance
List 5 characteristics of a pedigree which demonstrates an autosomal dominant inheritance pattern.
Both sexes are equally affected; both sexes transmit to offspring; disease is present in all generations (although an individual may have been undaignosed 2/2 mild phenotype, incomplete penetrance, or age-related penetrance); every affected child has a parent with the disorder; fathers can transmit to sons.
Which Mendelian inheritance pattern has a high “spontaneous” mutation rate?
Autosomal dominant disorders have a high spontaneous mutation rate and, therefore, there are more people who present with a disorder and no accompanying family history.
What risk factor increases the likelihood of a child having a new/spontaneous autosomal dominant mutation?
Increased paternal age
If an unaffected parent has more than one child with a new autosomal dominant condition, what should be suspected of the parent?
That they have germline mosaicism for the AD disorder.
What is germline mosaicism?
When a parent carries a gene mutation in gonadal tissue and germline cells but not somatic cells. The parent would not have signs of disease, but their children are at increased risk of inheriting the condition.
List 5 characteristics of a pedigree which demonstrates an autosomal recessive inheritance pattern.
No history of disease in prior generations; males and females are equally affected; males and females can each transmit the altered allele; the risk for two heterozygotes to have an affected offspring is 1/4 (however, two heterozygotes can also have offspring who are all affected or all unaffected); consanguinity increases the risk of having offspring with an AR disorder.
What is dosage compensation?
This is the inactivation of one of the two X chromosomes in each cell early in female embryonic life, which means that despite the extra X chromosome in females, they have the same amount of X-linked gene products as males.
Which form of classic Mendelian inheritance does not have Male-to-Male transmission?
X-linked disorders
Which form of classic Mendelian inheritance has a father passing the disease allele to all of his daughters and none of his sons?
X-linked disorders
What is somatic mosaicism?
This is the result of the random inactivation of the second X chromosome in each cell in females. If the two X chromosomes produce different phenotypes, the mosaicism may be visible in the patient.
What is hemizygosity?
This refers to males; since they only have one X chromosome, they are considered to be hemizygous for every allele at each locus on the X-chromosome. This means that if a male inherits an X-linked allele for a disease, he will be affected.
List 4 characteristics of a pedigree which demonstrates an X-linked recessive inheritance pattern.
There is never male-to-male transmission; if a generation has only females, the disease will appear to have skipped that generation; an affected father transmits the disease allele to all his daughters but none of his sons; carrier females have a 50% chance of transmitting the disease to each son.
What is genomic imprinting? Describe an example.
Genomic imprinting refers to differences in gene expression that depend on whether the disease allele is inherited from the mother or the father. The classic example is Prader Willi (microdeletion inherited from father) vs Angelman (same microdeletion, but from mother).
What is uniparental disomy?
Uniparental disomy occurs if both copies of a chromosome - or a piece of a chromosome - are inherited from only one parent.
How might uniparental disomy result in a child developing Prader Willi or Angelman syndrome?
If the child inherits both copies of chromosome 15 from either the mother or the father, it’s functionally the same as if they inherited a deletion from the parent whose chromosomal material is missing. The result is Prader Willi/Angelman.
How is mitochondrial inheritance unique?
Mitochondrial inheritance is unique because the ovum, not the sperm, transmits all the mitochondria to their zygote. Therefore, a mother carrying a mitochondrial DNA mutation passes it on to all her offspring, whereas the father carrying the mutation passes it on to none of his offspring.
List 5 disorders which have mitochondrial inheritance.
Myoclonic Epilepsy and Ragged-Red Fibers (MERRF), Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), Leigh syndrome, Kearns-Sayre syndrome, and Pearson syndrome.
What is the inheritance pattern and typical clinical picture associated with Myoclinic Epilepsy and Ragged-Red Fibers (MERRF)?
It is a mitochondrial disorder associated with progressive myoclonic epilepsy, myopathy, dementia, and hearing loss.
What is the inheritance pattern associated with MELAS, and what are its typical clinical findings?
It is a mitochondrial disorder (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) that presents anytime from toddlerhood to adulthood.
