Maps 1 Distance measured in Morgans M 2 Distance measured in Morgans M Physical MapsActual structure of genetic materialAt highest level DNA sequenceDistance measured in 10bp Mbp Genetic and ID: 942565
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Maps 1 Genetic MapsOrder and location of markers assigned to chromosome on the basis of linkage analysis Distance measured in Morgans (M) 2 Distance measured in Morgans (M) Physical MapsActual stru
cture of genetic materialAt highest level DNA sequenceDistance measured in 10bp (Mbp) Genetic and physical maps are usually linked together Example of a mapCattle chromosomes 1-5, from Cattle Genome
Database hosted at the Queensland Biosciences Precinct: http://www.cgd.csiro.au 4 Genetic mapsMap distance is determined from the number of observed recombination events 1cM = 1 recombination event per
100 meiosis (simple mapping function) Map distance versus rOnly odd number of crossover events are observedr = probability of an odd-number of cross-over events1-r = probability of an even number of
cross-over events, including zero 6
Mapping functionsMapping functions predict the number of crossover events from observed recombination eventsAlso account for interference (where a recombination event in one r
egion affects the likelihood of a 7 event in one region affects the likelihood of a recombination event in a closely aligned region) Different Mapping functions Haldaneassumes no interference (cross
overs occur randomly and independently over the entire chromosome )M = -(ln(1-2r))/2Kosambiassumes moderate interference (i.e. some crossover interference at adjacent sites) 8 interference at adjace
nt sites) M = ¼ ln (1+2r/1-2r)Simpleassumes complete interference r = M Comparison of mapping functions 1.21.41.61.8 Map distance (M) Simple Haldane Kosambi 9 0.20.40.60.800.10.20.30.40.50.6Recombin
ation frequency (r) Map distance (M) Kosambi Construction of linkage mapsSimple example is 3 point testcross(see lecture notes) 10 Construction of linkage mapsIn practice genetic maps are often constru
cted from complex pedigrees First need to determine parental phase, such that 11 First need to determine parental phase, such that gametes can be classed as recombinant or non-recombinantTypical
ly usea maximum likelihood approach Construction of linkage mapsIdentification of recombinant gametes is easier iflinkage phase of parents is knownSire AaBb x Dam AABB 9 AABB, 1 AaBB, 1 AABb, 9 AaBb
Sire thus gave gametes in frequency 0.45 AB, 0.05 aB, 0.05 Ab, 0.45ab Most likely phase is AB ab 12 Most likely phase is AB ab haplotype of gametes transmitted from parents to offspring is knownA
aBb x AABB AaBb, sire gave ab dam gave ABAaBb x AaBb AaBb, cannot determine transmitted haplotypes Physical mapsCytogenetic mapsbanding pattern observed under light microscopy of stained chromosomes
low resolution (only estimates of the number of bp) 13 Human Karyotype Talking glossary of genetics, 2008 Human Karyotype Talking glossary of genetics, 2008 Physical mapsRadiation hybridUse breaks i
nduced by radiation to determine the distance between two markers 16 Physical maps continuedSequence tag sites (STS)STS are short, unique DNA sequences with known location Sequence maps 17 Sequen
ce maps the ultimatenow available for a number of livestock species 18 Relationship between genetic and physical distanceNo universal relationship Comparison of human genetic and sequence based ph
ysical maps, Yu et al. Recombination rates varied greatly along each chromosome, from 0 to at least 9centiMorgans per megabase 19Various depending onspecies chromosomal region: crossovers often su
ppressed at centromeres, telomeresSex: female mammals usually have greater map distances than males, no crossover in male Drosophila Australian Sheep Gene Mapping Website 20 \n\n\r\r\n
\r\r \n Extract from Australian Sheep MapSheep Best Positions Linkage Map Version 4.4ChromosomeSex Av cMFemale cMMale cMLocus CodeMarker10.00.00.0\RM309 RM309A 114.26.622.5\BMS28
33 BMS2833 116.710.124.4\TGLA127 TGLA127 21116.710.124.4\INRA197 INRA197 116.710.124.4\MCM46 MCM46 119.012.526.6 PPT1 PPT 124.319.630.9\EPCDV022 EPCDV22 \n\n\r\r\n\r\r