1. Lecture 5: Genetic Variation and Inbreeding September 7, 2012

2. Announcements uI will be out of town Thursday Sept 20 through Sunday, Sept 24  No office hours uFriday, Sept 21: Prof. Hawkins will give a guest lecture about transposable elements

3. Computer Lab Access Schedule is posted on the door and on the website Hari will be holding his office hours in the lab Updated hours will be on class homepage

4. Last Time uHardy-Weinberg Equilibrium uUsing Hardy-Weinberg: Estimating allele frequencies for dominant loci uVariance of allele frequencies for dominant loci uHypothesis testing

5. Measures of Diversity are a Function of Populations and Locus Characteristics Assuming you assay the same samples, order the following markers by increasing average expected values of N e and H E : RAPD SSR Allozyme

6. Today uMore Hardy-Weinberg Calculations  Merle Patterning in Dogs uFirst Violation of Hardy-Weinberg assumptions: Random Mating uEffects of Inbreeding on allele frequencies, genotype frequencies, and heterozygosity

7. Example: Merle patterning in dogs Clarke et al. 2006 PNAS 103:1376 uMerle or “dilute” coat color is a desired trait in collies, shetland sheepdogs (pictured), Dachshunds and other breeds uHomozygotes for mutant gene lack most coat color and have numerous defects (blindness, deafness) uCaused by a retrotransposon insertion in the SILV gene

8. Example: Merling Pattern in collies Homozygous wild-type N=6,498 M1M1M1M1 Heterozygotes N=3,500 M1M2M1M2 Homozygous mutants N=2 M2M2M2M2 uIs the Merle coat color mutation dominant, semi-dominant (incompletely dominant), or recessive? uDo the Merle genotype frequencies differ from those expected under Hardy-Weinberg Equilibrium?

9. Why does the merle coat coloration occur in some breeds but not others? How did we end up with so many dog breeds anyway?

11. Nonrandom Mating: Inbreeding uInbreeding: Nonrandom mating within populations resulting in greater than expected mating between relatives uAssumptions (for this lecture): No selection, gene flow, mutation, or genetic drift uInbreeding very common in plants and some insects uPathological results of inbreeding in animal populations  Recessive human diseases  Endangered species http://i36.photobucket.com/albums/e4/doooosh/microcephaly.jpg

12. Important Points about Inbreeding uInbreeding affects ALL LOCI in genome uInbreeding results in a REDUCTION OF HETEROZYGOSITY in the population uInbreeding BY ITSELF changes only genotype frequencies, NOT ALLELE FREQUENCIES and therefore has NO EFFECT on overall genetic diversity within populations uInbreeding equilibrium occurs when there is a balance between the creation (through outcrossing) and loss of heterozygotes in each generation

13. Inbreeding can be quantified by probability (f) an individual contains two alleles that are Identical by Descent A1A2A1A2 A3A4A3A4 A1A3A1A3 A2A3A2A3 A3A3A3A3 A2A3A2A3 A1A2A1A2 A3A4A3A4 A1A3A1A3 A2A3A2A3 A3A5A3A5 A3A3A3A3 A2A3A2A3 Identical by descent (IBD) Identical by state (IBS) Identical by descent (IBD) P F1F1 F2F2

14. Nomenclature uD=X=P: frequency of AA or A 1 A 1 genotype uR=Z=Q: frequency of aa or A 2 A 2 genotype uH=Y: frequency of Aa or A 1 A 2 genotype up is frequency of the A or A 1 allele uq is frequency of the a or A 2 allele uAll of these should have circumflex or hat when they are estimates:

15. Effect of Inbreeding on Genotype Frequencies ufp is probability of getting two A 1 alleles IBD in an individual up 2 (1-f) is probability of getting two A 1 alleles IBS in an individual uInbreeding increases homozygosity and decreases heterozygosity by equal amounts each generation uComplete inbreeding eliminates heterozygotes entirely

16. Fixation Index uThe difference between observed and expected heterozygosity is a convenient measure of departures from Hardy-Weinberg Equilibrium Where H O is observed heterozygosity and H E is expected heterozygosity (2pq under Hardy-Weinberg Equilibrium)

17. uAssume completely inbred fraction (f) and noninbred fraction (1-f) in population uIf departures from Hardy Weinberg are entirely due to inbreeding, f can be estimated from Fixation Index, F IBD IBS

18. Effects of Inbreeding on Allele Frequencies uAllele frequencies do not change with inbreeding uLoss of heterozygotes exactly balanced by gain of homozygotes

19. Extreme Inbreeding: Self Fertilization uCommon mode of reproduction in plants: mate only with self uAssume selfing newly established in a population u½ of heterozygotes become homozygotes each generation uHomozygotes are NEVER converted to heterozygotes

20. Self Fertilization AA aa Aa A a aA Aa Self-Fertilizations AA A A AA AA Self-Fertilizations ½ Aa each generation ½ AA or aa (allele fixed within lineage) http://www.life.illinois.edu/ib/335/BreedingSystems/BreedingSystems.html

21. Decline of Heterozygosity with Self Fertilization uSteady and rapid decline of heterozygosity to zero AA or aa Aa

22. Partial Self Fertilization uMixed mating system: some progeny produced by selfing, others by outcrossing (assumed random) uRate of outcrossing = T uRate of selfing = S uT+S=1 uHeterozygosity declines to equilibrium point aa AA Aa

23. What determines the equilibrium frequency of heterozygotes in a population with mixed selfing and outcrossing?