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A A R H U S U N I V E R S I T E T Faculty of Agricultural Sciences Analysis of whole genome Analysis of whole genome association studies in association studies in pedigreed populations pedigreed populations Goutam Sahana Genetics and Biotechnology Faculty of Agricultural Sciences Aarhus University, 8830 Tjele, Denmark

Analysis of whole genome association studies in pedigreed populations

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Analysis of whole genome association studies in pedigreed populations. Goutam Sahana Genetics and Biotechnology Faculty of Agricultural Sciences Aarhus University, 8830 Tjele, Denmark. Concept of mapping. Identification of genetic variant underlying disease susceptibility or a trait value. - PowerPoint PPT Presentation

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  • Concept of mappingIdentification of genetic variant underlying disease susceptibility or a trait value = Causal variantEvidence for the location of the gene

  • Approaches to MappingCandidate gene studiesAssociationResequencing approaches

    Genome-wide studiesLinkage analysis Genome-wide association studies (Linkage disequilibrium, LD mapping)

  • Linkage mappingLook for marker alleles that are correlated with the phenotype within a pedigree

    Different alleles can be connected with the trait in the different pedigrees

  • Association mappingMarker alleles are correlated with a trait on a population level

    Can detect association by looking at unrelated individuals from a population

    Does not necessarily imply that markers are linked to (are close to) genes influencing the trait.

  • Linkage vs. associationEffectFreq. of causal variantVery difficultLinkage analysisUnlikely to existAssociation studyModified from D. Altschuler

  • Linkage vs. association Hirschhorn & Daly, Nature Rev. Genet. 2005

  • Allelic AssociationDirect AssociationAllele of interest is itself involved in phenotype

    Indirect AssociationAllele itself is not involved, but due to LD with the functional variant

    Spurious associationConfounding factors (e.g., population stratification)

  • Linkage disequilibriumNon random association between alleles at different loci. Loci are in LD if alleles are present on haplotypes in different proportions than expected based on allele frequencies

    Two alleles that are in LD are occurring together more often than would be expected by chance

  • Linkage disequilibriumLocus A: Alleles A & a; freq. PA & PaLocus B: Alleles B & b; freq. PB & PbPossible haplotyoesA

    BA

    ba

    Ba

    bExpected frequencies: pApB pApb papB papbObserved frequencies: pAB pAb paB pabD = pAB - pApB 0

  • LD variation across genomeThe extent of LD is highly variable across the genomeThe determinants of LD are not fully understood.Factors that are believed to influence LDGenetic driftPopulation growthAdmixture or migrationSelectionVariable recombination rates

  • HaplotypeGenotypes

    Locus12 4Locus21 3Locus33 2Locus44 1Locus52 3Locus61 2Identification of phase413122232431HaplotypesPHASE

    BEAGLE

  • Haplotype-based analysisIncreased ability to identify regions that are shared identical by descent among affected individuals

    Haplotypes may the causative composite allele rather than a particular nucleotide at a particular SNP

    Haplotype analysis is meaningful only if SNPS are in themselves in LD

  • Monogenic

    verses

    Complex traits

  • Monogenic traitMutation in single gene is both necessary and sufficient to produce the phenotype or to cause the disease

    The impact of the gene on genetic risk is the same in all families

    Follow clear segregation pattern in families

    Typically rare in population

  • Complex traitMultiple genes lead to genetic predisposition to a phenotype

    Pedigree reveals no Mendelian pattern

    Any particular gene mutation is neither sufficient nor necessary to explain the phenotype

    Environment has major contribution

    We study the relative impact of individual gene on the phenotype

  • Some examples

  • Quantitative TraitA biological trait that shows continuous variation rather than falling into distinct categories

    Quantitative trait locus (QTL) - Genetic locus that is associated with variation in such quantitative trait

  • Assessing genetic contributions to complex traitsContinuous characters (wt, blood pressure)Heritability: Proportion of observed variance in phenotype explained by genetic factors

    Discrete characters (disease)Relative risk ratio: = risk to relative of an affected individual/risk in general population encompasses all genetic and environmental effects, not just those due to any single locus

  • Factors that influence identification of allelic associationEffect sizeLinkage disequilibriumDisease and marker allele frequenciesSample Size

    Reviewed by Zondervar & Cardon, Nature Rev. Genet. 2004

  • Odds ratio

  • Sample sizeZondervar & Cardon (Nature Rev. Genet. 2004)No. of cases= no. of controls; D=0.7; power 80%; =0.001

  • Population stratificationConsider two case/control samples, genotyped at a marker with alleles M and mSample A2 NS2 NSSample B

  • Population stratificationSample ASample B2 =14.8

    P

  • Dealing with population structureGenomic control (Devlin and Roeder, 1999)Inflate the distribution of the test statistic by . estimated from data

  • Dealing with population structureStructured association (Pritchard et al., 2000)Discover structure from set of unlinked markers, i.e. assign probabilities of ancestry from k populations to each individual, and then control for it.

  • Association analysis approachesCasecontrol studies Markers frequencies are determined in a group of affected individuals and compared with allele frequencies in a control population

    Family based methods Based on unequal transmission of alleles from parents to a single affected child in each family. Associations are summed over many unrelated families

  • Case-Control studies: 2 testGenotypesAlleles2x3 contingency table2x2 contingency tableTest of independence:2 = (O-E)2/E with 2 or 1 df

  • Family based testsGenotypes from independent family trios where the child is affected

    Use the non-transmitted genotypes or alleles as internal controls to the transmitted ones

  • Family-based association studies

    1 4 transmitted

    2 3 non-transmitted??1 23 41 4control

    Is an allele transmitted more often than its not transmitted to affected offspring ?

  • TDT: Transmission Disequilibrium TestG/GG/gG/gNon-transmitted G gTransmittedG

    ga b

    c dTDTG = (TG-NTG)2/(TG+NTG)

    =(b-c)2/(b+c) ~ 21

  • TDT: Transmission Disequilibrium TestMultiallelic markersETDT (Sham & Curtis, 1995)Missing parent genotypesTRANSMIT (Cayton,1999)HaplotypesTDTHAP (Clayton & Jones, 1999)SibsTDT/STDT (Spielman & Ewens, 1998)PedigreesPBAT (Martin et al, 2000)Quantitative traitsQTDT (Abecasis et al. 2000)

  • Some limitationsSubjects random or structure familyParents not availableDifficult when there are very many genes individually of small effectEnvironmental influence may obscure genetic effectsGenetic heterogeneity underlying disease phenotypeHidden (unaccounted) relationship

  • Rare alleleSingle family is segregating

    AaOffspring group IOffspring group IIBb

  • Complex pedigree & Quantitative traits

  • Complex pedigreeNon-independence among pedigree membersOnly polygenic relationship is not sufficientAssociation analysis should account for the point-wise relationship among individualsIdentical-by-decent probabilities

  • Methods Combined linkage and LD Generalized linear modelsMixed-model (Yu et al. 2006)Bayesian approach

  • Combined linkage and LDPolygene the whole relationship in pedigree is used Identical-by-descend coefficients were estimated for point-wise relationship

    Phenotype= Fixed factors + Polygene + HaplotypePhase determination - GDQTLQTL mapping - DMU

  • QTL for Clinical Mastitis in cattleLA

    Chart1

    1.744403

    2.544403

    2.844403

    2.944403

    3.044403

    3.044403

    3.044403

    2.444403

    1.944403

    1.944403

    1.844403

    2.044403

    2.244403

    2.444403

    3.544403

    3.144403

    2.944403

    2.944403

    3.844403

    7.544403

    10.644403

    10.944403

    11.744403

    12.344403

    12.944403

    13.534403

    13.144403

    10.144403

    12.144403

    11.944403

    10.944403

    10.444403

    9.944403

    9.944403

    10.744403

    10.644403

    8.944403

    5.844403

    5.144403

    5.444403

    6.244403

    6.844403

    6.844403

    5.544403

    LA

    Morgan

    LRT

    profile_M1_90h10

    3.70E-0210110.132350.14670.62276.43E-033.49E-026.19E-031013.3444032.3444033.70E-021011.61.744403-0.00

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    0.253251010.64.92E-020.321510.614657.81E-041.25E-026.26E-031013.3444032.7444030.261010.52.8444031.44

    0.290251010.16.40E-020.283270.621831.18E-031.41E-026.17E-031013.3444033.2444030.290251010.42.944403-0.00

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    0.4871010.63.48E-020.338810.623373.92E-041.09E-026.09E-031013.3444032.7444030.704251003.210.144403-0.00

    0.5181009.54.54E-020.315710.625145.09E-041.13E-026.05E-031013.3444033.8444030.7171001.212.144403-0.00

    0.58551005.47.20E-020.266180.623557.47E-041.24E-026.14E-031013.3444037.9444030.7221001.411.944403-0.00

    0.64351006.95.10E-020.301990.628963.89E-041.05E-025.96E-031013.3444036.4444030.7311002.410.9444030.56

    0.65425-141371.71E-060.408790.623361.55E-099.57E-036.13E-031013.34440300.7351002.910.444403-0.00

    0.6631010.51.78E-020.368020.629418.12E-059.16E-035.85E-031013.3444032.8444030.74751003.49.944403-0.00

    0.671751009.11.29E-020.380570.629195.04E-058.90E-035.76E-031013.3444034.2444030.74351003.49.944403-0.00

    0.6741008.31.34E-020.372360.63394.77E-058.66E-035.63E-031013.3444035.0444030.77151002.610.744403-0.00

    0.6821009.12.18E-020.375630.619449.80E-059.24E-035.92E-031013.3444034.2444030.7971002.710.6444030.10

    0.690751010.51.55E-020.357370.643626.36E-058.55E-035.55E-031013.3444032.8444030.810251004.48.944403-0.00

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    0.894251004.83.67E-020.355180.605542.35E-041.06E-026.35E-031013.3444038.5444031.77

    0.909751006.26.11E-020.278480.6296.37E-041.18E-025.97E-031013.3444037.144403-0.00

    0.9511007.65.74E-020.291790.624376.92E-041.22E-026.07E-031013.3444035.744403-0.00

    profile_M1_90h10

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    LDLA

    LA

    LD

    QTL Profile-Mast-Red-

  • QTL for Clinical Mastitis in cattleLALD

    Chart1

    1.744403-0.000000032

    2.544403-0.000000032

    2.8444031.4432015598

    2.944403-0.0000000321

    3.0444030.58485429

    3.0444030.531389156

    3.044403-0.0000000321

    2.4444030.0272408303

    1.9444030.2057662723

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    2.0444030.0162969604

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    7.544403-0.0000757402

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    LA

    LD

    Morgan

    LRT

    profile_M1_90h10

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    0.377951012.25.73E-030.394260.625383.43E-059.61E-036.10E-031013.3444031.1444030.389751011.32.0444030.02

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    0.378851012.41.16E-020.376370.630611.12E-049.77E-035.99E-031013.3444030.9444030.429251009.83.5444031.06

    0.38051012.31.57E-020.371310.628541.56E-049.97E-036.02E-031013.3444031.0444030.4421010.23.1444032.18

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    0.398251012.95.52E-030.405350.61775.18E-059.90E-036.26E-031013.3444030.4444030.5181009.53.844403-0.00

    0.398751012.78.11E-030.402630.616196.66E-051.00E-026.29E-031013.3444030.6444030.58551005.87.544403-0.00

    0.399251013.14.42E-030.402730.621384.65E-059.79E-036.18E-031013.3444030.2444030.64351002.710.644403-0.00

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    0.42475-44746.35E-070.408790.623373.17E-099.58E-036.13E-031013.34440300.6631001.611.744403-0.00

    0.42525-3992.22.17E-060.408780.623376.74E-099.57E-036.13E-031013.34440300.671100112.344403-0.00

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    0.442-5266.21.40E-070.408790.623361.61E-099.58E-036.13E-031013.34440300.682999.8113.534403-0.00

    0.46351010.33.84E-020.331540.623364.51E-041.12E-026.08E-031013.3444033.0444030.690751000.213.144403-0.00

    0.4871010.63.48E-020.338810.623373.92E-041.09E-026.09E-031013.3444032.7444030.704251003.210.144403-0.00

    0.5181009.54.54E-020.315710.625145.09E-041.13E-026.05E-031013.3444033.8444030.7171001.212.144403-0.00

    0.58551005.47.20E-020.266180.623557.47E-041.24E-026.14E-031013.3444037.9444030.7221001.411.944403-0.00

    0.64351006.95.10E-020.301990.628963.89E-041.05E-025.96E-031013.3444036.4444030.7311002.410.9444030.56

    0.65425-141371.71E-060.408790.623361.55E-099.57E-036.13E-031013.34440300.7351002.910.444403-0.00

    0.6631010.51.78E-020.368020.629418.12E-059.16E-035.85E-031013.3444032.8444030.74751003.49.944403-0.00

    0.671751009.11.29E-020.380570.629195.04E-058.90E-035.76E-031013.3444034.2444030.74351003.49.944403-0.00

    0.6741008.31.34E-020.372360.63394.77E-058.66E-035.63E-031013.3444035.0444030.77151002.610.744403-0.00

    0.6821009.12.18E-020.375630.619449.80E-059.24E-035.92E-031013.3444034.2444030.7971002.710.6444030.10

    0.690751010.51.55E-020.357370.643626.36E-058.55E-035.55E-031013.3444032.8444030.810251004.48.944403-0.00

    0.693751013.21.86E-030.403110.625331.37E-059.52E-036.08E-031013.3444030.1444030.8271007.55.844403-0.00

    0.694251013.21.57E-030.405040.624181.19E-059.56E-036.11E-031013.3444030.1444030.84851008.25.144403-0.00

    0.69475-201371.71E-060.408780.623371.74E-099.57E-036.13E-031013.34440300.86551007.95.444403-0.00

    0.69525-217534.35E-070.408790.623378.07E-109.58E-036.13E-031013.34440300.881007.16.244403-0.00

    0.704251006.52.71E-020.3150.657061.16E-048.13E-035.23E-031013.3444036.8444030.894751006.56.8444030.33

    0.7171007.21.25E-020.349220.649953.65E-058.18E-035.36E-031013.3444036.1444030.909751006.56.8444030.48

    0.7221010.68.27E-030.385280.629342.82E-059.15E-035.89E-031013.3444032.7444030.9511007.85.544403-0.00

    0.7311004.73.08E-020.30030.663771.23E-047.57E-034.96E-031013.3444038.6444031.70

    0.73925998.444.35E-020.396760.593962.70E-049.40E-036.00E-031013.34440314.9044038.94

    0.740751000.72.89E-020.359220.626561.16E-048.45E-035.51E-031013.34440312.6444033.41

    0.74351004.52.52E-020.345970.641839.93E-058.11E-035.33E-031013.3444038.8444031.29

    0.77151002.37.32E-020.263810.6236.50E-041.20E-026.15E-031013.34440311.044403-0.00

    0.798251005.43.07E-020.339660.627761.77E-049.73E-035.92E-031013.3444037.944403-0.00

    0.810251004.46.21E-020.270220.634835.22E-041.11E-025.89E-031013.3444038.944403-0.00

    0.8271008.32.49E-020.353260.627281.48E-049.73E-035.98E-031013.3444035.044403-0.00

    0.84851007.45.72E-020.273680.640435.88E-041.13E-025.78E-031013.3444035.9444030.20

    0.86551008.83.05E-020.351950.620062.51E-041.05E-026.18E-031013.3444034.544403-0.00

    0.881006.65.50E-020.29710.623885.27E-041.14E-026.06E-031013.3444036.744403-0.00

    0.894251004.83.67E-020.355180.605542.35E-041.06E-026.35E-031013.3444038.5444031.77

    0.909751006.26.11E-020.278480.6296.37E-041.18E-025.97E-031013.3444037.144403-0.00

    0.9511007.65.74E-020.291790.624376.92E-041.22E-026.07E-031013.3444035.744403-0.00

    profile_M1_90h10

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    LDLA

    LA

    LD

    QTL Profile-Mast-Red-

  • QTL for Clinical Mastitis in cattleLALD/LALD

    Chart1

    2.3444031.744403-0.000000032

    2.9444032.544403-0.000000032

    2.7444032.8444031.4432015598

    3.2444032.944403-0.0000000321

    0.0444033.0444030.58485429

    0.5444033.0444030.531389156

    3.3444033.044403-0.0000000321

    1.8444032.4444030.0272408303

    1.6444031.9444030.2057662723

    0.5444031.944403-0.0000095168

    1.2444031.844403-0.0000265088

    1.1444032.0444030.0162969604

    0.2444032.2444030.0185906067

    3.2444032.4444031.1206260126

    0.9444033.5444031.0601634282

    1.0444033.1444032.1779390253

    0.5444032.944403-0.0001126592

    0.3444032.944403-0.0000075699

    0.4444033.844403-0.0000236027

    0.6444037.544403-0.0000757402

    0.24440310.644403-0.0000096231

    2.64440310.944403-0.000000032

    011.744403-0.00018067

    012.344403-0.0002281395

    012.944403-0.0000682414

    013.534403-0.0000101858

    3.04440313.144403-0.0000286556

    2.74440310.144403-0.0000163377

    3.84440312.144403-0.0000277397

    7.94440311.944403-0.0000000319

    6.44440310.9444030.5649934652

    010.444403-0.0002960709

    2.8444039.944403-0.0000073671

    4.2444039.944403-0.000440445

    5.04440310.744403-0.0000316191

    4.24440310.6444030.1017906115

    2.8444038.944403-0.0000471483

    0.1444035.844403-0.0000482385

    0.1444035.144403-0.000115464

    05.444403-0.0000128659

    06.244403-0.0000537135

    6.8444036.8444030.3325767712

    6.1444036.8444030.4817941532

    2.7444035.544403-0.0000388472

    8.6444031.6982511022

    14.9044038.9376605056

    12.6444033.4113730654

    8.8444031.28536918

    11.044403-0.000000032

    7.944403-0.0000278023

    8.944403-0.0000572169

    5.044403-0.0000372763

    5.9444030.1964023707

    4.544403-0.0001490375

    6.744403-0.0000270704

    8.5444031.772013477

    7.144403-0.0000093862

    5.744403-0.0000000319

    LDLA

    LA

    LD

    Morgan

    LRT

    profile_M1_90h10

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    0.290251010.16.40E-020.283270.621831.18E-031.41E-026.17E-031013.3444033.2444030.290251010.42.944403-0.00

    0.327251013.31.60E-030.408480.621133.24E-059.73E-036.19E-031013.3444030.0444030.326251010.33.0444030.58

    0.327751012.85.48E-030.406690.616444.75E-059.93E-036.27E-031013.3444030.5444030.3291010.33.0444030.53

    0.34710105.52E-020.302370.620588.68E-041.29E-026.19E-031013.3444033.3444030.3471010.33.044403-0.00

    0.371011.51.62E-020.38230.618521.38E-041.01E-026.18E-031013.3444031.8444030.371010.92.4444030.03

    0.3751011.71.66E-020.380560.619751.46E-041.01E-026.18E-031013.3444031.6444030.3751011.41.9444030.21

    0.376751012.87.03E-030.390730.626527.12E-059.78E-036.09E-031013.3444030.5444030.376751011.41.944403-0.00

    0.377651012.16.89E-030.383230.632184.23E-059.46E-035.98E-031013.3444031.2444030.38051011.51.844403-0.00

    0.377951012.25.73E-030.394260.625383.43E-059.61E-036.10E-031013.3444031.1444030.389751011.32.0444030.02

    0.378251013.12.80E-030.39690.62832.62E-059.59E-036.06E-031013.3444030.2444030.41011.12.2444030.02

    0.378551010.12.07E-020.329240.653311.30E-048.88E-035.50E-031013.3444033.2444030.4121010.92.4444031.12

    0.378851012.41.16E-020.376370.630611.12E-049.77E-035.99E-031013.3444030.9444030.429251009.83.5444031.06

    0.38051012.31.57E-020.371310.628541.56E-049.97E-036.02E-031013.3444031.0444030.4421010.23.1444032.18

    0.389751012.81.63E-020.375340.624222.65E-041.05E-026.09E-031013.3444030.5444030.46351010.42.944403-0.00

    0.3977510136.11E-030.405960.616545.79E-059.94E-036.28E-031013.3444030.3444030.4871010.42.944403-0.00

    0.398251012.95.52E-030.405350.61775.18E-059.90E-036.26E-031013.3444030.4444030.5181009.53.844403-0.00

    0.398751012.78.11E-030.402630.616196.66E-051.00E-026.29E-031013.3444030.6444030.58551005.87.544403-0.00

    0.399251013.14.42E-030.402730.621384.65E-059.79E-036.18E-031013.3444030.2444030.64351002.710.644403-0.00

    0.4121010.74.18E-020.322870.625085.94E-041.18E-026.08E-031013.3444032.6444030.654751002.410.944403-0.00

    0.42475-44746.35E-070.408790.623373.17E-099.58E-036.13E-031013.34440300.6631001.611.744403-0.00

    0.42525-3992.22.17E-060.408780.623376.74E-099.57E-036.13E-031013.34440300.671100112.344403-0.00

    0.42925-5266.21.40E-070.408790.623361.61E-099.58E-036.13E-031013.34440300.6741000.412.944403-0.00

    0.442-5266.21.40E-070.408790.623361.61E-099.58E-036.13E-031013.34440300.682999.8113.534403-0.00

    0.46351010.33.84E-020.331540.623364.51E-041.12E-026.08E-031013.3444033.0444030.690751000.213.144403-0.00

    0.4871010.63.48E-020.338810.623373.92E-041.09E-026.09E-031013.3444032.7444030.704251003.210.144403-0.00

    0.5181009.54.54E-020.315710.625145.09E-041.13E-026.05E-031013.3444033.8444030.7171001.212.144403-0.00

    0.58551005.47.20E-020.266180.623557.47E-041.24E-026.14E-031013.3444037.9444030.7221001.411.944403-0.00

    0.64351006.95.10E-020.301990.628963.89E-041.05E-025.96E-031013.3444036.4444030.7311002.410.9444030.56

    0.65425-141371.71E-060.408790.623361.55E-099.57E-036.13E-031013.34440300.7351002.910.444403-0.00

    0.6631010.51.78E-020.368020.629418.12E-059.16E-035.85E-031013.3444032.8444030.74751003.49.944403-0.00

    0.671751009.11.29E-020.380570.629195.04E-058.90E-035.76E-031013.3444034.2444030.74351003.49.944403-0.00

    0.6741008.31.34E-020.372360.63394.77E-058.66E-035.63E-031013.3444035.0444030.77151002.610.744403-0.00

    0.6821009.12.18E-020.375630.619449.80E-059.24E-035.92E-031013.3444034.2444030.7971002.710.6444030.10

    0.690751010.51.55E-020.357370.643626.36E-058.55E-035.55E-031013.3444032.8444030.810251004.48.944403-0.00

    0.693751013.21.86E-030.403110.625331.37E-059.52E-036.08E-031013.3444030.1444030.8271007.55.844403-0.00

    0.694251013.21.57E-030.405040.624181.19E-059.56E-036.11E-031013.3444030.1444030.84851008.25.144403-0.00

    0.69475-201371.71E-060.408780.623371.74E-099.57E-036.13E-031013.34440300.86551007.95.444403-0.00

    0.69525-217534.35E-070.408790.623378.07E-109.58E-036.13E-031013.34440300.881007.16.244403-0.00

    0.704251006.52.71E-020.3150.657061.16E-048.13E-035.23E-031013.3444036.8444030.894751006.56.8444030.33

    0.7171007.21.25E-020.349220.649953.65E-058.18E-035.36E-031013.3444036.1444030.909751006.56.8444030.48

    0.7221010.68.27E-030.385280.629342.82E-059.15E-035.89E-031013.3444032.7444030.9511007.85.544403-0.00

    0.7311004.73.08E-020.30030.663771.23E-047.57E-034.96E-031013.3444038.6444031.70

    0.73925998.444.35E-020.396760.593962.70E-049.40E-036.00E-031013.34440314.9044038.94

    0.740751000.72.89E-020.359220.626561.16E-048.45E-035.51E-031013.34440312.6444033.41

    0.74351004.52.52E-020.345970.641839.93E-058.11E-035.33E-031013.3444038.8444031.29

    0.77151002.37.32E-020.263810.6236.50E-041.20E-026.15E-031013.34440311.044403-0.00

    0.798251005.43.07E-020.339660.627761.77E-049.73E-035.92E-031013.3444037.944403-0.00

    0.810251004.46.21E-020.270220.634835.22E-041.11E-025.89E-031013.3444038.944403-0.00

    0.8271008.32.49E-020.353260.627281.48E-049.73E-035.98E-031013.3444035.044403-0.00

    0.84851007.45.72E-020.273680.640435.88E-041.13E-025.78E-031013.3444035.9444030.20

    0.86551008.83.05E-020.351950.620062.51E-041.05E-026.18E-031013.3444034.544403-0.00

    0.881006.65.50E-020.29710.623885.27E-041.14E-026.06E-031013.3444036.744403-0.00

    0.894251004.83.67E-020.355180.605542.35E-041.06E-026.35E-031013.3444038.5444031.77

    0.909751006.26.11E-020.278480.6296.37E-041.18E-025.97E-031013.3444037.144403-0.00

    0.9511007.65.74E-020.291790.624376.92E-041.22E-026.07E-031013.3444035.744403-0.00

    profile_M1_90h10

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    LDLA

    LA

    LD

    QTL Profile-Mast-Red-

  • Simulation100 half-sib families (Dairy cattle pedigree)2000 progeny5 chromosomes 100 cM (each)SNP 5000 15 QTL (1QTL-10%, 4QTL-5 %, 10QTL2%)50% of the genetic varianceHeritability 30%

  • Generalized linear modelsPhenotype= Sire-family + genotypeSoftware TASSELhttp://www2.maizegenetics.net/index.php?page=bioinformatics/tassel

  • Generalized linear models

    Chart2

    0.1835

    0.2636

    3.3594

    1.3907

    0.8949

    0.3712

    0.0882

    4.0439

    0.8869

    0.6752

    0.5823

    0.8031

    1.8517

    0.5377

    0.6115

    0.22

    1.6107

    1.9395

    0.619

    0.7986

    0.7547

    0.4278

    0.3316

    0.18

    0.3717

    0.634

    1.3364

    0.9603

    1.8086

    0.2673

    2.3059

    0.2027

    1.3108

    4.3415

    0.52

    2.4894

    1.3029

    2.4428

    0.0904

    0.6761

    0.1139

    0.7447

    0.6525

    0.2554

    0.2585

    2.2808

    0.0945

    0.3285

    0.4672

    0.1376

    1.1145

    0.0274

    0.6086

    0.4685

    0.3832

    0.8612

    0.5131

    0.0484

    0.4784

    0.6376

    1.5405

    2.8763

    0.003

    4.4918

    1.8993

    0.9302

    0.4412

    0.2141

    0.2422

    4.9983

    0.5126

    1.867

    1.3569

    0.0364

    2.9332

    1.8811

    0.0761

    3.4407

    0.539

    0.965

    0.7968

    0.1367

    5.276

    0.5838

    0.0889

    2.9957

    0.8132

    1.6643

    6.088

    0.5927

    1.0552

    4.2731

    4.4297

    4.4438

    1.4274

    5.735

    0.0818

    0.2127

    3.507

    2.5715

    0.2778

    4.4835

    0.9507

    5.5326

    1.2107

    2.9911

    2.7318

    0.1502

    5.039

    5.5761

    3.787

    1.5422

    6.4463

    3.0693

    3.635

    0.501

    18.2455

    2.1251

    4.2093

    14.7655

    1.824

    18.6477

    1.7942

    14.6718

    32.1298

    4.5349

    0.508

    9.0343

    32.0644

    31.6787

    5.1224

    8.8595

    0.6955

    11.0301

    9.9566

    16.0237

    5.6114

    9.8432

    39.6404

    12.5848

    18.9746

    0.544

    14.5334

    3.0306

    23.6879

    12.6873

    14.0837

    0.1276

    41.6533

    29.5023

    3.9711

    10.8073

    11.6085

    19.0266

    106.7306

    11.8091

    35.1584

    3.2791

    2.5129

    0.0067

    7.7174

    5.1415

    5.6775

    6.1247

    17.2293

    7.4234

    19.4616

    2.435

    8.0326

    7.844

    2.2603

    19.3813

    0.0107

    5.7354

    9.6664

    2.0952

    2.8559

    4.9472

    4.7677

    2.8997

    1.4008

    5.5412

    9.7033

    17.2022

    7.1866

    0.5553

    4.5468

    6.3909

    3.5692

    1.2424

    3.8961

    3.1044

    2.3213

    1.057

    0.895

    1.098

    0.2042

    0.5901

    1.2198

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