MBLG2972 Lecture Notes - Lecture 12: Behavioural Genetics, Vasopressin Receptor 1A, Wild Type

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MBLG2072
Genetics and Genomics
Monica Zanuttini !
460381099
Lecture 12
Mapping of a heritable trait:!
1. QTL mapping: !
We start with two strains that dier strongly in the trait of interest (a saturated genetic map i.e.
has a recombinant frequency less than 0.5). E.g. fat and skinny mouse, aim to map the gene
which is associated with ‘fatness’. !
Get saturated genetic map, outlining micro satellite markers, with no section of the chromosome
which are more than 50 cM apart. !
Cross these two strains to form F1 heterozygote. Perform a male backcross (cross
heterozygous male to recessive female), to produce G2 progeny which are heterozygous and
homozygous recessive. !
Genotype all the mice at each available marker.!
Perform gel electrophoresis to determine which are homozygous at this locus and which are
heterozygous at that locus.!
Use the visible marker for ‘fatness’ to determine if there is a correlation between heterozygotes
and being ‘fat’. Can conclude that the gene of interest which controls ‘fatness’ is located near
the mapped gene. !
If visible marker is random with heterozygosity, then we can see that the marker is not involved
with ‘fatness'. !
If we analyse 350 markers with a 5% level of significance, we expect 0.05*350 = 17.5 significant
associations (gene of interest shows significance, however it is not even close to the marker). In
this case we should make the significance threshold very low (<0.001) but this false discovery
rate can fail to recognise something as significant. !
Instead, use interval mapping: seek pairs of linked markers
that show evidence of a QTL between them. !
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