Color Plates. (a) (c) Crossover

Transcription

1 Color Plates igure 2.5. Pairwise D for 45 SNPs within a linked region (figure from GENESTAT, meb.ki.se/genestat/, courtesy of the Swedish National Biobanking program, Wallenberg consortium north). (b) Gene conversion (a) D E D' d' E' e' ' f' d e f D e D' d' e' e' ' f' f d e (c) Crossover D E f D' d' E' e' f' ' d e igure 2.6. A simplistic diagram showing the major difference between gene conversion and crossover. (A) Two DNA molecules. (B) Gene conversion after mismatch correction the red DNA donates part of its genetic information (e e' region) to the blue DNA. (C) DNA crossover the two DNAs exchange part of their genetic information (f f ' and ').

2 igure 4.1. Nonsequencing SNP discovery methods: heteroduplex analysis, TILLING, DGGE, and SSCP. Target DNA (allele T)...NNNNNACGTACGTACGTACGTTCGTACGTACGTNNNNN... NGCATGCATGCA Invader probe TGCATGCATGCATGCAA Allele-specific (T) secondary Quencher probe lap ACCGGTATAO CLEAVAGE luorescence emission Target DNA (allele G)...NNNNNACGTACGTACGTACGTGCGTACGTACGTNNNNN... NGCATGCATGCA Invader probe TGCATGCATGCATGCAA lap Quencher ACCGGTATAC NO CLEAVAGE The Invader TM assay Target DNA (allele T)...NNNNNACGTACGTACGTACGTTCGTACGTACGTNNNNN... NGCATGCATGCA TGCATGCATGCATGCAA Invader probe ACCGGTATAC luorescence emission Allele-specific (T) secondary lap 1 probe CLEAVAGE Quencher RET probe CLEAVAGE Target DNA (allele G)...NNNNNACGTACGTACGTACGTGCGTACGTACGTNNNNN... NGCATGCATGCA TGCATGCATGCATGCAC Allele-specific (G) secondary probe lap 2 GTCTTAGCT luorescence emission CLEAVAGE RET probe Quencher CLEAVAGE The BiPlex Invader TM assay igure 5.2. The Invader assay.

3 Microarray plate Microarray plate -NNNNNACGTACGTACGTACGTGCGTACGTACGTNNNNN NNNNNTGCATGCATGCATGCAAGCATGCATGCANNNNN No hybridization -NNNNNACGTACGTACGTACGTGCGTACGTACGTNNNNN NNNNNTGCATGCATGCATGCACGCATGCATGCANNNNN- Hybridization igure 5.3. Allele-specific oligonucleotide hybridization. A oligonucleotides feature with the SNP site in its central position is bound to a microarray glass plate. Under stringent hybridization conditions, the complementary allele will anneal to the fixed oligonucleotide and a fluorescent signal attached to the probe will be detected. Targeted SNP (T/G) DNA Polymerase Target DNA (allele T) NNNNNACGTACGTACGTACGTTCGTACGTACGTNNNNN TGCATGCATGCATGCA A Target DNA (allele G) NNNNNACGTACGTACGTACGTGCGTACGTACGTNNNNN TGCATGCATGCATGCA C Complementary ddntp labelled with a Oligonucleotide primer fluorescent dye igure 5.5. Minisequencing or primer extension. An oligonucleotide primer immediately flanking the SNP is extended using a DNA polymerase. luorescently labeled terminating nucleotides are incorporated, with a different dye color for every nucleotide. The oligonucleotide can be attached to a solid-phase array, separated in a capillary electrophoresis system, by a flow cytometry instrument, by mass spectrometry, or revealed by a fluorescent plate reader.

4 An example of a genealogy for three copies of a short chromosomal segment. Tracing the segmental lineages back in time, the following events occur: 1, the green lineage under- goes recombination and splits into two lineages, which are then traced separately; 2, one of the resulting green lineages coalesces with the magenta lineage, creating a segment, part of which is ancestral to both green and magenta, part of which is ancestral to magenta only; 3, the blue lineage coalesces with the lineage created by event 2, creating a segment that is partially ancestral to blue and magenta, partially ancestral to all three colours; 4, the other part of the green lineage coalesces with the lineage created by event 3, creating a segment that is ancestral to all three colours in its entirety. The recombination event induces different genealogical trees on either side of the break: these are shown in the inserted figure. Reprinted from Trends in Genetics 18, Nordborg, M. and Tavaré, S., Linkage disequilibrium: what history has to tell us, Pages No.83 90, Copyright (2002), with permission from Elsevier. igure 8.1. Example genealogy illustrating the coalescent (Nordborg and Tavaré 2002).

5 INDEX A Additive variance, 234 Admixture - see Population admixture Allele additive effects of, 234 frequency, 34 selection, 99 -Specific Oligonucleotide (ASO) probe, 85 specific PCR amplification, 60, 82 Alzheimer disease, 3, 30, 134, 161 Amplicon sequencing, 60 Arabidopsis, 67 aspen, 63 birch, 63 maize, 61, 62 potato, 62, 63 soybean, 61 spruce, 63 wheat, 63 Amplified ragment Length Polymorphism (ALP), 64, 79, 95, 99, 201, 259 Ancient polyploidy, 44 Anchoring markers, 255 Asexual propagation, 251 Association genetics, 1-8 vs QTL mapping, 2 Association mapping approaches, 5, 260 definition, 12 impact on crops, 254, 258 statistical concepts, 103 B Balancing selection, 34, 45, 252 Bayes factor, 115 calculation for simulated TDT data, 169 calculation for S-TDT, 166 calculation for TDT, 165 comparison with P-value, 136 definition, 157, 176 Bayesian hypothesis testing - see Hypothesis testing Bayesian BIC, 119, 143 Bonferroni correction, 112 Breast cancer, 3 Breeding efficiency, 251 populations, 259 selection, 252 BUGS, 143,

6 272 INDEX C Candidate gene approach, 5, 22, 62, 78, 104, 150, 217, 224, 227 -based markers, 64 mapping, 98, 205 selection, 229 Case-control - see Experimental design case control Chi-square, 109 Cinnamoyl CoA Reductase (CCR), 151, 217, 261 Cleaved Amplified Polymorphic Sequence (CAPS), 54, 99 Clonal forestry, 233, 236, 237, 242 Coadapative gene complexes, 26, 242 Coalescent, 134, 140, 143 Coding regions, 44, 46, 80, 231 Colon cancer, 3 Complex diseases and traits, 4, 7, 12, 30, 41 Conformational Polymorphisms, 54, Crop domestication, 33, 42, 90, 234 Cultivar identification, 97 D D and D, 13, 17, 65 Degenerate oligonucleotide primed- PCR (DOP-PCR), 79 Deleterious mutations, 32 Deletions - see indels, Denaturing Gradient Gel Electrodiversity causes phoresis (DGGE), 54, 82 Denaturing high-performance liquid chromatography (dhplc), 56, 82 Derived CAPS markers, 54, 82 Diabetes, 3, 28 Dimorphism, 253 Direct sequencing complications, 60 Disease resistance, 3, 6, 45, 63, 101, 214, 237, 258 Diversity Array Technology (DArT), 79, 95 Diversity causes of - see Genetic of DNA chip technology, 57 pooling, 56 sequence polymorphism - see polymorphisms Domestication - see crop domestication E EcoTILLING, 56 Elite population, 97, 235 EM algorithm, 22 Epistatic interactions, 7, 25, 143, 242 Experimental design 7, 119, 145, 224 case-controls, 5, 121, 157, 182 choice, 129 power, 120, 148, 222, 225 sample size, 6, 163, 190 TDT, 5, 124, 161, 164 unstructured populations vs TDT, 227 Expressed Sequence Tag database - see Genomic resources ESTs alse discovery rate (DR), 112 alse positives, 112 alse negatives, 114 amily based design, 5 amily-wise error rate (WER), 112 ine mapping - see mapping resolution isher s exact test, 123 orage species breeding characteristics, 251, 252 genome structure, 198 taxonomy, 198 orest tree species characteristics, 212 generation time, 254 status of crop, 213 synteny, 213 ounder effect, 25, 34, 42 unctional Polymorphic Nucleotide - see Quantitative Trait Nucleotide requentist, Hypotheses testing, 135 vs. Bayesian, 135

7 INDEX 273 G Gene Assisted Selection (GAS), 211 benefits of, 219 integration with breeding, 263 Gene conversion, 24, 30 Gene introgression, 101, 258, 264 Genetic architecture of trait, 3, 117, 221, 259 correlations, 235, 259 diversity, 6, 25, 32, 42, 97, 204 diversity causes of, 45 drift, 6, 25, 32, 45, 145, 234 load, 3, 213, 232, 236 mapping, 98 resources maps, 79, 201, 255 Genome Evolution, 96 sequencer 20 system, 57, size, 78, 255 structure allotetraploid, 199 structure diploid, 199 Genomic rearrangements, 29 resources ESTs, 42, 64, 100, 200, 214, 229, 255 resources large insert libraries, 34, 60, 200, 256 status of crop, 254 Genotype X Environment interaction, 7, 212, 226, 241 Genotyping invader assay, 84 Gibbs sampling, 137, 180 GoldenGate PCR technology, 80, 90 Graphical Overview of LD (GOLD), 22 H Haplotype blocks, 21, 29, 30, 44, 216, 227 confidence scoring of SNPs, 69 conservation across species, 205 cummulative selection pressure, 49 diversity, 31 estimation, 140 frequencies, 21 mapping, 62, 144, 257, 262 megagametophytes and - see megagametophytes, mixed models for, 139 Heteroduplex-based polymorphisms, 54 Heterotic groups, 97 High-throughput genotyping, 84, 87, 219 Hitch-hiking, 25, 32, 45 Hom(o)eologous loci, 61, 67, 77, 204 Homogeneous MassCleave (hmc), 58 Homoplasy, 98, 204 Horticultural crops breeding characteristics, 252 characteristics, 250 economic impact, 251 generation time, 254 Human HapMap, 5, 31 Hypotheses testing Bayesian, 113, 135 requentist, 111, 135 I Identity By Descent (IBD) probabilities, 139, 184 Inbreeding control of, 255 depression, 44, 236 Indels, 48, 60, 95 Arabidopsis thaliana, 42, 57 barley, 49 maize, 48 melons, 49 potato, 49, 62 rice, 43, 49 transposons and, 48 Insertions and deletions - see indels, In silico SNP detection see SNP detection In silico, Isozyme loci, 97, 215 L Likelihood, 22, 106, 137, 155 Linkage analysis, 4, 30, 104, 259 Linkage Disequilibrium (LD) age of allele, 6 Arabidopsis, 34

8 274 INDEX bottlenecks, 6, 25, 79, 146 combined with linkage mapping, 224 decay, 6, 14, 33, 34, 205 definition, 12 disease resistance, 34, 214 drift, 6, 25, 145 Drosophila melanogaster, 31 estimates, 106 examples, 21, 27, 126, 127, 156, 158, 189 forest trees, 217 genome size and, 256 genome wide patterns, 6, 22, 79, 253 genomic status, 254 high LD populations, 6, 30, 48 hot spots, 22, 31 human, 29 human selection, 6 inbreeding species, 28, 30, 60, 198 low LD species, 36, 216 maize, 33 mapping, 1 measures, 16 methylation and, 23 multi-gene complexes and, 253 Norway spruce, 48 outbreeding species, 42, 227, 253 Perennial ryegrass, 206 physical linkage, 1, 6 pine, 47 comparison of plant species, 36 ploidy and, 255 population size and, 6 population structure, 6, 26, 36 recombination rate, 6, 23, 29 selection and, 6, 26 sex determining chromosomes and, 27, 253 soybean, 28, 98 SSRs and, 33 vs QTL mapping, 5 Linkage Equilibrium, 12 departures from Hardy-Weinberg, 221 Linkage phase, 22, 62, 237, 241, 255, 259 Low heritability traits, 99, 128 M MALDI-TO MS, 58, 77 Map-based cloning - see positional cloning Mapping resolution, 6, 98, 104, 259 Marker trait associations, 5, 64, 89, 205, 213, 228, 240, 267 -QTL associations, 4, 64, 238 Marker Assisted Selection (MAS), 99 approach with LD, 260 autogamous species, 63 outbreeding species, 64, 204 versus GAS, 217 within-family selection only, 238 with SNPs, 99 Markov Chain Monte Carlo (MCMC), 119, 137, 182 MassArray, 58 Mating systems selfing species - see Selfing species outcrossing species - see Outcrossing species Megagametophytes, 47, 60, 215 Metropolis sampling, 137, 172 Microarray, 57, 214, 229 complexity-reduction genotyping, 80 Microfibril angle, 151, 217, 229 Migration, 25 Minisequencing, 87 Molecular marker comparisons, 96 Multi-locus models, 114, 139, 143 Multiple Displacement Amplification (MDA), 79 Mutation, 23 N Natural selection signatures of, 31 Non-coding regions, 44

9 INDEX 275 Non-synonymous substitutions, 45, 216, 231 Nucleotide diversity, 7, 42, 63, 216 KETO and ENOL forms, 47 O Odds prior, 105, 126, 137, 152 posterior, 137, 149, 225 ratio, 19, 159 Oligonucleotide Ligation Assay (OLA), 86 Outcrossing species, 217, 264 forage, 205 forest trees, 217 human, 29 maize, 33 P P-value definition, 111 problems, 112,120, 130, 134, 144, 151, 156 Paralogous loci, 42, 44, 60, 63, 66 Pea, 3 Pedigreed populations, 5, 217, 226 Phylogenetic analysis, 98, 198 Physical mapping, 98 Plus tree selection, 220, 233 Polymorphism, enzymatic cleavage scoring, 58, 83 haplotype-tagged, 226 recombination rate and, 29, 45 Polyploidy, 255 Population, admixture, 5, 18, 27, 122, 145, 180, 182, 221, 223, 266 factors affecting structural analysis, 191 history, 12, 31, 139, 145, 221 isolation, 42 size, 6, 25, 145, 184, 204 effect of size on deleterious mutation, 46 structure, 5, 26, 122, 181, 204, 229, 232, 255 structure analysis of, 191 structure analysis of population admixture, 182 subdivision, 145 unstructured, 2, 5, 217, 224 Positional cloning Brix tomato, 3 Cry2 Arabidopsis, 3 rigida Arabidopsis, 3 fw2.2 tomato, 3 Heading date 1 rice, 3 Lin5 tomato, 3 teosinte branch 1 maize, 3 Power calculation Bayesian, 148 requentist, 147 using lddesign, 154 Primer extension technique - see mini-sequencing Prior and posterior distributions, 115, 136, 144, 149, 156, 172, 187, 195 Production partition model, 143 Production population, 234, 237 Protein expression, 230 Pyrosequencing, 57, 81, 87 Q Qualitative trait nucleotides, 48 Quantitative genetics skills, 213, 241 trait nucleotides, 19, 211 trait nucleotides causative, 2, 48, 218, 252 trait variation, 3, 80 Quantitative Trait Locus (QTL) combined with LD mapping, 187, 208 compared with LD mapping, 104 differential expression, 190, 231 mapping, 1, 89, 98, 104, 150, 184, 187, 215, 225 R R function, 107, 152, 170 lddesign, 152

10 276 INDEX r 2, 18, 65, 206, 217 Random Amplified Polymorphic DNA (RAPD), 95, 99, 217, 261 Recombination, 22 effective rate in selfing species, 28 events, 6 hot-spots, 29 rate, 6, 29 Resequencing, 57 Restriction ragment Length Polymorphism (RLP), 54, 79, 96, 99, 203 Reverse transcriptase error, 69 S S-TDT, 126, 165 SDT, 126 Sample size, 145, 155 Selection among families, 205, 217, 238 among families outcrossing effect on, 223 backward, 235, 237, 242 bias, 118, 120, 153, 226 forces on SNPs, 32 forward, 235, 237, 234 within family, 220, 238 Selfing species 253 Arabidopsis thaliana, 28, 34 soybean, 28 Self-incompatibility, 253, 254 Sequence variation, 41 Sexual dimorphism - see dimorphism Simple Sequence Repeat (SSR) markers, 33, 46, 64, 67, 79, 96, 99 Single eature Polymorphism (SP), 80 Single Nucleotide Polymorphism (SNP) abundance, 41, 45, 96 ADH, 100 β amylase, 87, 100 applications, 95 Arabidopsis thaliana, 57, 78, association with genetic disorder, 5, 42 association with important genes, 48 autogamous vs allogamous, 63 barley, 43, 46, 61, 82, 87, 97, 100 beet, 44 biallelic, 5, 22, 41, 148 cassava, 44, 47, 99 coding regions, 46 comparative species identification, 70 confidence measures, 69 definition, 41 deleterious, 45, 46 detection In silico, 67 detection of LD, 48 detection software, 61, 69 direct sequencing detection, 60 discovery, 42, 46, 53, 231 discovery perennial ryegrass, 63, 201 discovery white clover, 66, 201 disease resistance, 214 distribution, 44 diversity, 42 dwarfing, 100 ESTs and, 45, 64 EST mapping, 99 evolution and, 98 fitness penalty, 45 flanking SSRs, 46 frequency, 42, 61 genetic drift, 45 genotype scoring methods, 81 genotyping, 56, 77 haplotypes, 48, 62, 80 haplotype confidence scoring, 69 high density maps, 42 inbreeding species, 43 Japanese sugi, 62 linkage phase - see Haplotype Lotus japonicus, 56 maize, 43, 46, 62, 97, 99 melons, 46, 98 methylation and, 47, 48 mutation rate, 23, 41, 45 neutrality, 45 non-coding regions, 46, 49 outbreeding species, 42, 43, 62, 83 pearl millet, 46 PCR error and, 60

11 INDEX 277 pine, 47, 57, 62, 101 poplar, 43, 56 potato, 44, 48, 57, 62, 63 preferential target regions, 46 prevalence, 96 purine salvage, 100 quinoa, 44, 46, 47, 101 recombination rate and, 45 removal of deleterious, 45 rice, 43, 46, 47, 49, 100 soybean, 42, 46, 61, 98, 100 stability, 41, 49 sugarcane, 100 Tongkat Ali, 97 variation non-coding region, 45 Waxy gene, 100 wheat, 56, 63, 67, 83, 97, 100 within gene, 49, 100, 241 Single stranded Conformational polymorphism (SSCP), 46, 54, 82 SNP - see single nucleotide polymorphism SNaPshot assay, 87, 88 SNuPe technique, 65, 88, 100 Spurious association, 5, 7, 12, 27, 60, 111, 126, 133, 144, 164, 180, 206 Statistical inference, 110, 115 Statistical models, 134 Bayesian methods of selection, 115, 143 STRAT, 122, 144, 182 Susceptibility genes human disease, 30 Synonymous substitutions, 45, 216 Synteny, 212, 261 T Tandem selection, 252 Taqman technology, 85 TDT - see Experimental design TDT Technology transfer, 261 Temperature Gradient Gel Electrophoresis (TGGE), 54 Targeting Induced Local Lesions IN Genomes (TILLING), 56, 83 teosinte branch 1, 3, 62 Transcript mapping, 98 Transitions, 41, 47 Transposons and mutation, 48, 97 Transversions, 47 Type 1 error, 110, 112, 224, 260 Type 2 error, 260 V Validation rate of SNPs, 65 Varietal development base populations, 200 polycrossing, 200, 203 synthetic populations, 200 W Whole genome scans, 6, 31, 78, 98, 111, 123, 149, 205, 262 Arabidopsis thaliana, 78, 98 ALPs, 203 Perennial ryegrass, 205