Non-Mendelian Inheritance Flashcards
De novo mutations are most common from what origin?
Almost all cases of a new mutation arise from a gamete of one parent
If a couple had a pregnancy with a rare genetic mutation observed in the fetus, what would you say to them with regards to future pregnancies?
Once a rare genetic event has occurred, there is an increased risk for recurrence. This increased risk may be high or low but it is no longer the same as the overall population risk.
Mosaicism
- Gonadal
- Somatic
- Gonadal mosaicism is the presence of 2 or more populations of cells with different genotypes in sperm or ova but not the rest of the body
- Somatic mosaicism is the presence of 2 or more populations of cells with different genotypes in somatic tissue and possibly gonadal tissue also
What is uniparental disomy
When both members of a pair of homologous chromosomes, or a segment of the pair, are inherited from the same parent with no chromosome of that pair from the other parent. Can be maternal or paternal.
What are the 2 sub-categories of UPD?
Isodisomy (2 copies of the exact same chromsome are inherited)
Heterodisomy (2 different copies of the chromosome are inherited)
Why does UPD occur?
In gametogenesis, it is possible for an ova or sperm to undergo non-disjunction and end up with 2 copies of the same chromosome in their gamete(s) instead of 1. When this gamete combines with a normal gamete from the mate, a trisomy occurs for that chromosome. Sometimes, the developing zygote undergoes trisomy rescue, in which one of these 3 chromosomes is degraded. If the lost chromosome happens to be from the normal mate, then both inherited copies of the chromosome in question would be from only one parent (the one who had the non-disjunction).
Why is UPD dangerous
1) It can expose recessive alleles
2) It can result in phenotypic problems if the chromosome involved has imprinted genes that need to be present from the parent whose chromosome was lost in trisomy rescue in order for the offspring to be normal
Explain 4 reasons why the phenotype below might be observed.
What is genetic imprinting
Either maternal or paternal copy of a gene is “stamped” or silenced during meiosis resulting in expression of only one copy of gene. In order for an offpsring to be normal, it must inherit one active copy and one silenced copy of imprinted genes.Approx. 1% of all genes in human genome are imprinted.
What is Prader - Willi Syndrome?
What can result in PWS?
What is it characterized by?
- There are 2 loci on chromsome 15 that are involved; one that is called the Prader Willi gene and the other is the angelman syndrome gene. In ova, the locus of the PW gene is imprinted and the locus of the AS gene is not. The opposite is true in sperm. In order for an offpspring to not develop PW, their mother’s chromosome must be imprinted for PW and normal for AS genes and their father’s chromosome must be imprinted for AS gene and normal for PW gene.
- Causes:
- Maternal UPD
- Deletion of the father’s AS - PW loci on chromosome 15
- Defects with imprinting
- Hypotonia, excessive eating (unable to stop eating), behavioral problems, short stature, intellectual disability
What is Klinefelter syndrome (KS)?
- 47,XXY or XXY
- Set of symptoms that result from two or more X chromosomes in males
What is Angelman Syndrome?
What can result in AS?
What is it characterized by?
- There are 2 loci on chromsome 15 that are involved; one that is called the Prader Willi gene and the other is the angelman syndrome gene. In ova, the locus of the PW gene is imprinted and the locus of the AS gene is not. The opposite is true in sperm. In order for an offpspring to not develop AS, their mother’s chromosome must be imprinted for PW and normal for AS genes and their father’s chromosome must be imprinted for AS gene and normal for PW gene.
- Causes:
- Paternal UPD
- Deletion of the mother’s AS - PW loci on chromosome 15
- Defects with imprinting
- De novo mutation
- Severe intellectual disability, inability to speak, ataxic (uncoordinated) gait, seizures, microcephaly, inappropriately happy
Mitochondrial Inheritance
- # genes in mtDNA and what they encode?
- Connection to nucleus?
- 37 genes, mostly encode for rRNA or tRNA, remainder encode for subunits of OxPhos
- Most proteins and RNAs in mitochondria are made from transcripts from nucleus
What parts of the body are most affectd by mitochondrial disorders?
Brain and muscle
Pleiotropy is always present in mutations in mtDNA. Why?
Mitochondria undergo fission to replicate. During this process, their DNA is segregated randomly into daughter organelles, so there is a high degree of random inheritance of mtDNA during mitochondrial replication. As such, a single mutation in mtDNA can result in a wide array of phenotypic expression depending on how much of the mutated DNA is present in their mitochondria. This is described as homoplasmy (all mitochondria have identical genomes) vs. heteroplasmy (there is a mix of DNA populations within one cell’s mitochondria). As such, there is a gradient of phenotypic expression.