9 Non-Mendelian Inheritence

Question 1

Mitochondria - MtDNA

Answer 1

Mitochondrial genome —> circular, dsDNA, unmethylated / multiple mitochondria pre cell and multiple genomes per mitochondria

Question 2

Neurospora Genetics

Answer 2

Poky mutant, slow growth

Excess of cytochrome c, lack of cytochrome a+b

No male and female crosses can define ‘maternal cytoplasm’

Question 3

Mitochondrial Disease examples

Answer 3

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

Question 4

Multiple mitochondria that have multiple copies of DNA ~13 genes…

Answer 4

For oxidative phosphorylation system protein subunits (remainder comes from the nucleus)

Hostile environment (free radicals) / lacks repair mechanism (+ few introns)

Question 5

Most common mitochondria mutation

Answer 5

Deletion on MtDNA

Question 6

Pathology of MtDNA mutants

Answer 6

Can alter different tissues and different tissues may have different thresholds of disease —> distribution of mutant and WT mtDNA will influence complementation

Question 7

Homoplasmy

Answer 7

all mitochondria have same genome

Question 8

Homoplasmic mutation

Answer 8

all mitochondria have mutation

Question 9

Heteroplasmic mutation

Answer 9

subset have mutation (caused by mitochondrial bottleneck)

Question 10

What does Heteroplasmy define (population)

Answer 10

a mixed population of mitochondrial disease in a single gene —> these can be inherited with uneven, unpredictable separation

Question 11

Mitochondrial bottleneck

Answer 11

1. Variety of mtDNA molecules in maternal pool
2. When generated, each oocyte receives a small sub sampling of mtDNA molecules in differing proportions.

Question 12

Cytoplasmic Segregation and Reconbindation

Answer 12

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

Question 13

Maternal spindle transfer

Answer 13

1. Mothers egg (unhealthy mitochondria) - nucleur material removed and kept
2. Donor egg (healthy mitochondria) - donor nucleur material removed and destroyed
3. Mothers nucleus places inside donor egg and fertilised

Question 14

Pro nucleur transfer

Answer 14

1. Parents fertilised egg (unhealthy mitochondria) - parents nucleur material removed and kept
2. Donors fertilised egg (healthy mitochondria) - donor nucleur material removed and destroyed
3. Parents nucleur material placed inside donor egg

Question 15

Chloroplasts

Answer 15

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

Question 16

Lethality

Answer 16

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°

Question 17

Complications to simple Mendelian Genetics

Answer 17

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

Question 18

Epigenetics - Methylation effects on gene expression

Answer 18

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

Question 19

Effects of methylation on transposition

Answer 19

Stops transposition

Question 20

Genomic imprinting

Answer 20

Caused by genetic lesion on crh15 —> region silences on maternal chromosome

Therefore any disruption to paternal chromosome (eg. Deletion) can develop the disease

Question 21

Maternal imprinting

Answer 21

Allele inherited from mother is transcriptionally silent and the paternally inherited allele is active