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Transcript
Empirical population genetics training course for beginners
Thierry De Meeûs
Time table
Interactions hôtes - vecteurs - parasites dans les infections par des trypanosomatidae - (INTERTRYP),
UMR IRD/CIRAD 177
WHO Collaborating Center for research on host/vector/parasite interactions
for surveillance and control of Human African Trypanosomiasis
Thierry de Meeûs
DR2 IRD
(+226) 20 97 00 94
 (+226) 76 86 40 88 (Burkina-Faso)
 (+33) (0)6 19 83 52 60 (France)
Fax: (+226) 20-97- 23-20
 [email protected]
Address in France: INTERTRYP, UMR 177 IRD/CIRAD, TA A-17/G, Campus International de Baillarguet,
34398, Montpellier Cedex 5, France.
Address in Burkina-Faso: CIRDES, 01 BP 454, Bobo-Dioulasso 01, Burkina-Faso.
--------------------------------------------------------------------------------------------DAY 1: 9H-10H30, Lecture 1.
General introduction
The context of population structure analyses, direct and indirect methods, genetic markers and sampling
strategies.
I. Notions of molecular biology and formal genetics.
1. DNA, the universal molecule of genetic information transmission, the molecule of life: Structure,
replication, puric and pyrimidic bases, the genetic code, chromosomes.
2. The three domains of life: Archaea, Bacteria and Eukaryota, origins, prokaryote genetics, eukaryote
genetics, mitosis, meiosis, gametes, isogamy and anisogamy, introns and exons.
3. Mutation, the key to genetic variation and evolution: point mutation, transition and transversion, insertions
and deletions, transposable elements and retroviruses, chromosome mutations.
4. Genetic variation: genotype and phenotype.
5. Genetic variation: mendelian heredity, complex traits and complementation, Morgan, recombination and
sex-linked traits, hybrids F1, F2, backcross and genetic distance.
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6. Inbreeding, kinship, relatedness and pedigrees.
DAY 1: 11H-12H30, Practical 1.
DAY 1: 15H-16H30, Lecture 2.
II. Population genetics.
1. The population the basic unit in ecology, a demographic notion.
2. The model of Hardy and Weinberg: Hardy-Weinberg proportions, Hardy-Weinberg equilibrium with two
alleles, with three alleles and with dominance.
3. Hardy-Weinberg when N small, genetic drift: inbreeding and genetic diversity evolution, experimental
examples.
4. Effective population size: Definitions, coalescence, separated genders (in large or small populations),
inbred or fluctuating sized populations.
5: More than one locus, linkage disequilibrium: definition, measure, evolution as a function of
recombination, relevant evolutionary forces.
DAY 1: 17H-18H30, Practical 2.
DAY 2: 9H-10H30, Lecture 3.
III. Alterations of Hardy-Weinberg proportions
1. Heterozygote deficits: Endogamy (selfing, sib-mating, homogamy), Wahlund effect, underdominance,
technical causes (null alleles, dropout, short allele dominance, stuttering).
DAY 2: 11H-12H30, Practical 3.
DAY 2: 15H-16H30, Lecture 4.
III. Alterations of Hardy-Weinberg proportions (continued).
2. Heterozygous excesses: Over-dominance, heterogamy, clonality, small dioecious populations, sex-biased
dispersal, technical causes (echo bands, duplicated loci).
IV. Wright's F-statistics.
1. Wright's Island model
2. Inside individuals relative to the sub-population they belong to: FIS.
3. Inside sub-populations relative to the total population: FST.
4. Inside individuals relative to the total population: FIT.
5. Definitions according to heterozygosity: Chesser and Nei, lower and higher bounds, interpretation.
6. Definitions according to inbreeding: Allele identity probabilities, Weir and Rousset.
7. Summing up.
DAY 2: 17H-18H30, Practical 4.
JOUR 3: 9H-10H30, Lecture 5.
V. Inferences.
1. Selfing.
2. Dispersal following a Wright's Island model with many Islands and many alleles: mutation insignificant or
not, standardized FST according to Hedrick or Meirmans.
3. Dispersal in a finite Island model (n small), with homoplasy (K small) and local selfing (s).
4. Dispersal in other models of populations, stepping-stone and neighborhood: stepping stones in one, two or
three dimensions, Rousset's model in one or two dimensions.
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5. Effective population size estimators.
6. Unbiased estimators for Wright's F-statistics.
7. F-statistics for more than three hierarchical levels.
8. F-statistics in clones.
VI. Statistical procedures
1. Definitions: P-value, null hypothesis, unilateral and bilateral tests, decision risk level, type 1 and type 2
errors, power and robustness.
2. F-statistics confidence intervals (CI): Bootstrap and Jackknife.
3. Significance testing through randomization: panmixia, differentiation, correlation between matrices
(Mantel), linkage disequilibrium, with more than three levels, comparison among groups,
comparison among categories of individuals.
4. Nested and orthogonal factors.
5. Procedures for combining k tests series.
6. Multivariate analyses.
7. Exploration of a hidden structure.
DAY 3: 11H-12H30, Practical 5.
DAY 3: 15H-16H30, Lecture 6.
VII. Real published examples
1. Population genetics of Ixodes ricinus and Lyme borreliosis in Switzerland.
2. Candida albicans in Abidjan (Ivory Coast).
Conclusions
DAY 3: 17H-18H30, End of lectures and practicals, Real data analyses demonstrations.
DAY 4: 9h-12h et 15h-18h, Analysis of a real data set by each attendant, assisted by the demonstrator
(continued). The data set can be brought by the attendants, otherwise a data set on cattle ticks
will be explored. Some time can also be saved for informal discussions at the very end of the
day.
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