9 Non-Mendelian Inheritence Flashcards
Mitochondria - MtDNA
Mitochondrial genome —> circular, dsDNA, unmethylated / multiple mitochondria pre cell and multiple genomes per mitochondria
Neurospora Genetics
Poky mutant, slow growth
Excess of cytochrome c, lack of cytochrome a+b
No male and female crosses can define ‘maternal cytoplasm’
Mitochondrial Disease examples
Leigh’s disease / Alpers disease / Barth syndrome
Faulty mitochondria have been linked to common medical problems including Parkinson’s, deafness, failing eyesight, epilepsy and diabetes
Multiple mitochondria that have multiple copies of DNA ~13 genes…
For oxidative phosphorylation system protein subunits (remainder comes from the nucleus)
Hostile environment (free radicals) / lacks repair mechanism (+ few introns)
Most common mitochondria mutation
Deletion on MtDNA
Pathology of MtDNA mutants
Can alter different tissues and different tissues may have different thresholds of disease —> distribution of mutant and WT mtDNA will influence complementation
Homoplasmy
all mitochondria have same genome
Homoplasmic mutation
all mitochondria have mutation
Heteroplasmic mutation
subset have mutation (caused by mitochondrial bottleneck)
What does Heteroplasmy define (population)
a mixed population of mitochondrial disease in a single gene —> these can be inherited with uneven, unpredictable separation
Mitochondrial bottleneck
- Variety of mtDNA molecules in maternal pool
- When generated, each oocyte receives a small sub sampling of mtDNA molecules in differing proportions.
Cytoplasmic Segregation and Reconbindation
Mitosis can result in a disproportionate number of mutant or wild type organelles in a daughter cell due only to random sampling error
Once this occurs, there is a higher chance of the more populous organelle replacing the less populous one
Since organelles are essentially haploid
There’s no complication of diploidy and its associated dominance/recessiveness
Maternal spindle transfer
- Mothers egg (unhealthy mitochondria) - nucleur material removed and kept
- Donor egg (healthy mitochondria) - donor nucleur material removed and destroyed
- Mothers nucleus places inside donor egg and fertilised
Pro nucleur transfer
- Parents fertilised egg (unhealthy mitochondria) - parents nucleur material removed and kept
- Donors fertilised egg (healthy mitochondria) - donor nucleur material removed and destroyed
- Parents nucleur material placed inside donor egg
Chloroplasts
Chloroplast genome —> circular, dsDNA, unmethylated / encodes genes for photosynthesis and the protein production pipeline to build these proteins / multiple chloroplasts per cell and multiple genomes per plasmid
Lethality
Recessive lethal genes / dominant lethal genes
Conditional lethal genes = can be sex linked (X linked) / mutants can be engineered that are functional at 30° but non-functional at 37°
Complications to simple Mendelian Genetics
Segregation of NUP88 (N) mutation - NUP88 involved in binding of microtubules to nucleur pore complex
NN and Nn - normal segregation / nn - cant be found
From Nn plants all male gametes are fine but 50% of female gametes die —> female n gametes don’t make enough protein and fail to segregate during meiosis
Epigenetics - Methylation effects on gene expression
Cytosie methylation within gene promoter regions is through to inhibit binding of regulatory proteins and repress transcription
Methylation with introns and exons is correlated with highly expressed genes
However methylation in the first exon is correlated with inhibition
Effects of methylation on transposition
Stops transposition
Genomic imprinting
Caused by genetic lesion on crh15 —> region silences on maternal chromosome
Therefore any disruption to paternal chromosome (eg. Deletion) can develop the disease
Maternal imprinting
Allele inherited from mother is transcriptionally silent and the paternally inherited allele is active
