Genetic Basis of Complex Inheritance Flashcards
what is mendelian inheritance?
- law of dominance and segregation
- law of independent assortment
- genes are passed from parents to children (dominant/recessive/ X linked etc)
what is non-mendelian inheritance?
- doesn’t fit Mendelian’s law
- involves gene conversion
- results in intermediate phenotype (black and white= grey)
- distribution of phenotypes not always as expected
what are 4 mechanisms of non-mendelian inheritance?
- Incomplete penetrance
- environmental factor
- genetic modifier - Genomic imprinting
- variants from parents - extranuclear inheritance
- mitochondrial mutations - anticipation
- triplet repeat expansion
what is the majority of mammalian inheritance in terms of non-mendelian inheritance?
incomplete penetrance and genomic imprinting
define penetrance
- 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)
in cystic fibrosis, where does the mutation occur?
in CFTR ( autosomal recessive mutation)
what does cystic fibrosis cause?
mucus to block ducts in liver, lungs and pancreas
where is cystic fibrosis most prevalent?
in northern European caucasians
what 2 factors influence the severity of disorders like CF?
- genetic modifiers (genes that have small quantitive effect on level of expression of another gene)
- environmental factors (lifestyle, diet, smoke, alcohol, drugs, stress, air pollution, chemicals, infection)
what are 3 examples of genetically caused disease?
- Huntington’s disease
- Haemophillia
- Osteogenesis imperfecta
what are the top 3 examples of environmentally caused disease?
- scurvy
- TB
- diabetes
define genetic imprinting
- 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
what are epigenetic modifications?
- 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
what are some common genetic mechanisms?
- deletions
- point mutations
- imprinting errors
- uniparental disomy (e.g. both chromosomes come from the same parent so active alleles have 2 copies of themselves)
what 3 things can cause UDP ( uniparental disomy)
- non-disjunction
- duplication
- recombination
what can gynogenic UPD cause? (2 maternal genomes)
- mass of embryo altered
- ovarian teratoma (with several germ layers)
what can androgenic UPD cause? ( 2 paternal genomes)
- mass of placenta altered
- hydatidiform mole (in womb)
what are some examples of human models of imprinting errors?
angelman syndrome, mental retardation, epilepsy, inappropriate laughter, short stature, marked obesity…and more
who is mitochondrial inheritance inherited from?
mother
why is mitochondrial inheritance only inherited from mother?
when gametes fertilise, sperm releases its nucleus and mitochondria which degrade so only maternal are kept
what inheritance factors does mitochondria have?
- circular
- contains 37 genes
- 2 rRNA, 22 tRNA nad 13 coding genes
does mitochondria have a low or high mutation rate
HIGH mutation rate
why is mitochondria the “hotspot” for mutations?
- lack of efficient DNA repair system
- lack of protective proteins such as histones
- damaged by reactive oxygen species (ROS) such as free radials
what type of tissues do mitochondrial disease affect the most?
affects tissues with high metabolic demand
