1. Types of genome maps Physical – based on bp Genetic/ linkage – based on recombination from Thomas Hunt Morgan's 1916 ''A Critique of the Theory of Evolution'', page 132,Thomas Hunt Morgan obtained from http://en.wikipedia.org/wiki/File:M organ_crossover_1.jpg

2. Linkage maps Unlinked markers may be far apart on the same chromosome, or on different chromosomes Linkage mapping involves determining the genetic distance between various genetic markers

3. Genetic markers Marker: “Any polymorphic Mendelian character that can be used to follow a chromosomal segment though a pedigree” Phenotypic vs. molecular Examples of molecular markers – RFLP, AFLP, RAPD, microsatellite (aka simple sequence repeats, SSR), SNP Dominant vs. codominant MM Mm mm MM mm

4. Genetic distance Measured in map units, or centimorgans (cM) Distance in which there is one recombination in every 100 meioses X

5. Genetic distance Recombination frequencies don’t exceed 50% Double recombinants are possible from Thomas Hunt Morgan's 1916 ''A Critique of the Theory of Evolution'', page 132,Thomas Hunt Morgan obtained from http://en.wikipedia.org/wiki/File: Morgan_crossover_2.jpg

6. Genetic distance Recombination frequencies don’t exceed 50% Double recombinants are possible http://nitro.biosci.arizona.edu/courses/EEB320-2005/Lecture14/pics/haldane.GIF

7. Mapping functions Need to relate recombination fraction with mapping distance Haldane’s mapping function (1919) Kosambi’s mapping function (1944) http://nitro.biosci.arizona.edu/courses/EEB320-2005/Lecture14/pics/haldane.GIF

8. Mapping functions Interference: crossing over at one point reduces the probability of crossing over nearby Haldane’s mapping function (1919) – Assumes no interference Kosambi’s mapping function (1944) – Adjusts for interference

9. Mapping Relationship between genetic distance and physical distance is not constant (variation in cM/ MB) Recombination hotspots Mapping distances may vary between sexes

10. (a) Male- and female-specific autosomal recombination linkage map of great reed warbler (based on 43 microsatellite markers) Hansson B. et.al. Proc. R. Soc. B 2005;272:2289-2298 ©2005 by The Royal Society http://en.wikipedia.org/wiki/ File:Reed_warbler_cuckoo.jpg

11. Mapping Relationship between genetic distance and physical distance is not constant (variation in cM/ MB) Recombination hotspots Mapping distances may vary between sexes Distinction between linkage groups and chromosomes

12. Mapping with phenotypic markers Marker 1 % Recombination ± standard error or (Number of progeny analysed) Marker 2 aromC20 [estimate]acuJ aromC26 [estimate]trpB sconB715acuJ211 sconB724galD5 acuJ2113.7 (450)fpaB37 http://www.gla.ac.uk/ibls/molgen/aspergillus/maps.html

13. Genotypes vs. haplotypes Genotype: combination of alleles at one marker Haplotype: combination of alleles at multiple loci on a chromosome Genotypes leave some ambiguity about underlying haplotype, and whether recombination happened Marker informativeness

14. Linkage disequilibrium Linkage: close physical proximity between two loci Linkage disequilibrium: non-random association of alleles at two or more loci, not necessarily on the same chromosome Linkage disequilibrium can be caused by non- random mating, population structure, as well as physical linkage

15. Mapping crosses and pedigrees Crosses and pedigrees create linkage disequilibrium over large distances Fewer markers are needed Examples – F2 – Backcross – Pedigree

16. How do you map? Use software! E.g., crimap Use genome sequence as a guide Use other species as a guide Start with 2-point comparisons between pairs of markers

17. Statistical concepts Likelihood LOD score – logarithm of the odds LOD = log10( probability of observed data if there is linkage with  = x ) probability of observed data if there is no linkage,  = 0.5 Maximum likelihood