Inheritance Flashcards
Mendel’s law of uniformity
-if two plants differ in just one trait and they are crosse then the resulting hybrids will be uniform in the chosen trait
-not always true
DD x dd= Dd
Mendel’s law of segregation
-two heterozygous parents result in 3 possible types of offspring
Dd xDd= DD or Dd Dd or dd
Mendel’s law of independent assortment
-different pairs of alleles are passed to offspring independently of each other. The result is that new combinations of genes present in neither parents are possible
DdHh x ddhh= DdHh ddHh Ddhh ddhh
Autosomal dominant disorders
- mutant allele is dominant over the normal allele and results in disease expression
- heterosygous individuals with two different alleles with express the disease
- the offspring have a 50% chance of inheriting the chromosome carrying the disease allele and therefore also having the disease
- if both parents are heterozygous then the recurrence risk is 75%
Incomplete penetrance
- may occur is patients have a dominant disorder but it does not manifest itself clinically in them
- this gives the appearance of the gene having ‘skipped ‘ a generation
- this increases the likelihood of having an unaffected child
Variable expression
- refers to differences in severity of the disease expressed
- a mildly affected parent may have a severely affected child
Autosomal recessive disorders
- these only manifest themselves when an individual is homozygous for the disease allele
- parents are generally unaffected but are carriers
- there is usually no family history but skipping may be seen
- if both parents carriers then 1/4 chance of having disease, 2/4 chance of being a carrier, 1/4 chance of being normal
- consanguinity increases risk
- often enzymatic
Sex-linked disorders
- genes carried on X chromosome are X-linked and can be dominant or recessaive
- normally males inherit and X chromosome and a Y chormosome. The Y chromosome contributes very less genetic material to a man’s genetic makeup so X-inactivation occurs in females to maintain the balance (and make one X weaker)
- when an X chromosome is inactivated it is seens as a highly condensed Barr body in the nuclei of interphase cells
- X inactivation is random so some Xs will be from the father and some from the mother
- inactivation occurs via DNA methylation
- trisomy X has 2 barr bodies as 2 Xs have been switched off
X-linked recessive disorder
- if a recessive disease-causing mutation occurs on the single X chromosome ina man it is sufficient to cause disease
- women would need a double identical mutation for disease expression which is very rare
- but if during random X inactivation, if most X chromosomes carrying normal alleles are inactivated (called unfavourable lyonisation) then these females can manifest with the disease phenotype- manifesting heterozygotes
- male to male is not seen
- if carrier female mates with nromal male then half of the sons will be affected and half of daughters will be carriers e.g haemophilia, duchene and androgen insensitivity syndrome
X-linked dominant disorders
- rare
- vitamin D resistant rickets
- females are more likely to inherit it due to more XX
- seen in successive generations
- heterozygous female mating a normal male will result in 50% of sons being affected and 50% daughters being affected
- this is Rett’s syndrome- inherited in X-linked dominant fashion
Mitochondrial inheritance
-mitochondrial DNA is wholly inherited from the ovum
- no introns in the fenes so any mutation has a high chance of having an effect
-most mitochondrial diseases are myopathies or neuropathies
MELA (mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke syndrome) and Leber hereditary optic neuropathy
Trinucleotide expansions
- trinucleotide repeats cause unstable gene sites e.g fragile X, Friederick Ataxia, Huntington Chorea and Mytonic dystrophy
- anticipation is seen where the disease develops earlier with greater severity in successive generations
Fragile X
- CGG repeat
- X-linked
- accounts for lots of cases of mental retardation in males
- expansion of CGG near the FRM1 gene causes this and over 52 repeats destabilises the sequence and over 200 results in phenotype
- men more affected by females and have enlarged testes, prominent ear lobes, protracting jaw, high pitched voice and mental retardation
- if there are lots of repeats but no phenotype then these people are premutation carriers and are at risk of intention tremor and ataxia
- anticipation seen
Huntingtons
- autosomal dominance
- expanded and unstable CAG repeat on short arm of chromosome 4- 4p16.3
- this results in translation of glutamine sequence in huntingtin
Myotonic dystrophy
- CTG is expanded
- anticipation is higher if inherited form mother as oogenisis has longer dormacy and results in much higher instability
