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: !
ā€¢We start with two strains that diļ¬€er 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 ā€˜fatnessā€™. !
ā€¢Get saturated genetic map, outlining micro satellite markers, with no section of the chromosome
which are more than 50 cM apart. !
ā€¢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. !
ā€¢Genotype all the mice at each available marker.!
ā€¢Perform gel electrophoresis to determine which are homozygous at this locus and which are
heterozygous at that locus.!
ā€¢Use the visible marker for ā€˜fatnessā€™ to determine if there is a correlation between heterozygotes
and being ā€˜fatā€™. Can conclude that the gene of interest which controls ā€˜fatnessā€™ is located near
the mapped gene. !
ā€¢If visible marker is random with heterozygosity, then we can see that the marker is not involved
with ā€˜fatness'. !
ā€¢If we analyse 350 markers with a 5% level of signiļ¬cance, we expect 0.05*350 = 17.5 signiļ¬cant
associations (gene of interest shows signiļ¬cance, however it is not even close to the marker). In
this case we should make the signiļ¬cance threshold very low (<0.001) but this false discovery
rate can fail to recognise something as signiļ¬cant. !
ā€¢Instead, use interval mapping: seek pairs of linked markers
that show evidence of a QTL between them. !
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