Genetic Basis of Complex Inheritance

Question 1

what is mendelian inheritance?

Answer 1

• law of dominance and segregation
• law of independent assortment
• genes are passed from parents to children (dominant/recessive/ X linked etc)

Question 2

what is non-mendelian inheritance?

Answer 2

• doesn’t fit Mendelian’s law
• involves gene conversion
• results in intermediate phenotype (black and white= grey)
• distribution of phenotypes not always as expected

Question 3

what are 4 mechanisms of non-mendelian inheritance?

Answer 3

1. Incomplete penetrance
   - environmental factor
   - genetic modifier
2. Genomic imprinting
   - variants from parents
3. extranuclear inheritance
   - mitochondrial mutations
4. anticipation
   - triplet repeat expansion

Question 4

what is the majority of mammalian inheritance in terms of non-mendelian inheritance?

Answer 4

incomplete penetrance and genomic imprinting

Question 5

define penetrance

Answer 5

• frequency with which a trait is manifested by individuals carrying the gene
• proportion of individuals carrying a particular gene
  (e. g. mutant population has a much higher risk of having a mutant gene than normal population)

Question 6

in cystic fibrosis, where does the mutation occur?

Answer 6

in CFTR ( autosomal recessive mutation)

Question 7

what does cystic fibrosis cause?

Answer 7

mucus to block ducts in liver, lungs and pancreas

Question 8

where is cystic fibrosis most prevalent?

Answer 8

in northern European caucasians

Question 9

what 2 factors influence the severity of disorders like CF?

Answer 9

1. genetic modifiers (genes that have small quantitive effect on level of expression of another gene)
2. environmental factors (lifestyle, diet, smoke, alcohol, drugs, stress, air pollution, chemicals, infection)

Question 10

what are 3 examples of genetically caused disease?

Answer 10

• Huntington’s disease
• Haemophillia
• Osteogenesis imperfecta

Question 11

what are the top 3 examples of environmentally caused disease?

Answer 11

• scurvy
• TB
• diabetes

Question 12

define genetic imprinting

Answer 12

• genes expressed from only one chromosome
• some genes are modified when passed on from parents
• it’s not a mutation but a diffference in pattern they express
• e.g. certain genes can be inherited from father but then silenced/shut off (imprinted) and allele from mother is expressed instead

Question 13

what are epigenetic modifications?

Answer 13

• heritable changes in gene functions that can’t be explained by changes in DNA sequences but instead heritable changed to DNA (active/non active)
• genes switched on/off through DNA methylation

Question 14

what are some common genetic mechanisms?

Answer 14

1. deletions
2. point mutations
3. imprinting errors
4. uniparental disomy (e.g. both chromosomes come from the same parent so active alleles have 2 copies of themselves)

Question 15

what 3 things can cause UDP ( uniparental disomy)

Answer 15

1. non-disjunction
2. duplication
3. recombination

Question 16

what can gynogenic UPD cause? (2 maternal genomes)

Answer 16

• mass of embryo altered

- ovarian teratoma (with several germ layers)

Question 17

what can androgenic UPD cause? ( 2 paternal genomes)

Answer 17

• mass of placenta altered

- hydatidiform mole (in womb)

Question 18

what are some examples of human models of imprinting errors?

Answer 18

angelman syndrome, mental retardation, epilepsy, inappropriate laughter, short stature, marked obesity…and more

Question 19

who is mitochondrial inheritance inherited from?

Answer 19

mother

Question 20

why is mitochondrial inheritance only inherited from mother?

Answer 20

when gametes fertilise, sperm releases its nucleus and mitochondria which degrade so only maternal are kept

Question 21

what inheritance factors does mitochondria have?

Answer 21

• circular
• contains 37 genes
• 2 rRNA, 22 tRNA nad 13 coding genes

Question 22

does mitochondria have a low or high mutation rate

Answer 22

HIGH mutation rate

Question 23

why is mitochondria the “hotspot” for mutations?

Answer 23

• lack of efficient DNA repair system
• lack of protective proteins such as histones
• damaged by reactive oxygen species (ROS) such as free radials

Question 24

what type of tissues do mitochondrial disease affect the most?

Answer 24

affects tissues with high metabolic demand

Question 25

what 4 diseases are mitochondrial disease? (passed through mitochondrial DNA)

Answer 25

1. 3 major myopathies
   - MERRF (muoclonic epilepsy with ragged red fibres)
   - MELAS (mitochondrial myopathy encaphalomyopathy lactic acidosis , stroke-like symptoms)
   - CPEO (chronic progressive external ophthalmoplegia)
2. Leber’s hereditary optic neuropathy (loss of central vision)
3. Leigh’s syndrome (encephalopathy)
4. DAD (diabetes mellitus and deafness)

Question 26

define anticipation (genetic meaning)

Answer 26

• disease presents at earlier age and/or is increasing in severity in succeeding generations
• severity of onsets increases in next generations (becomes worse and worse)
• only occurs if repeat of disease is extraordinarily high

Question 27

what are some examples of anticipation disease ( get worse in severity from generation to generation)

Answer 27

1. Huntington’s disease
2. Myotonic dystrophy (causes muscle loss)
3. Fragile X syndrome