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by: Favian Swaniawski

Populatn BIOL 464

Favian Swaniawski
GPA 3.82

Stephen DiFazio

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Stephen DiFazio
Class Notes
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This 82 page Class Notes was uploaded by Favian Swaniawski on Saturday September 12, 2015. The Class Notes belongs to BIOL 464 at West Virginia University taught by Stephen DiFazio in Fall. Since its upload, it has received 37 views. For similar materials see /class/202736/biol-464-west-virginia-university in Biology at West Virginia University.


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Date Created: 09/12/15
Lecture 5 Linkage Disequilibrium September 5 2008 holn nlrl O39Old exams posted at Esfimafing linkage disequilibrium l u mpulg l m us in HQWdyDVl ml Q g lquullblsnum be l W Scallfllplll lg CE l Ql ZYQ MS md vlelml ml leulm Mews flue 39quot f A s w l Wher39e n is The number of alleles cl a locus and p is The frequency of allele 39 Tl l s is Q mmmm le mvemlceml f summem zl We 183 Coy Lllrl l vers l y in p pulm m A when lleles we eque ll quot 1 1 n l Wher39e Ni i is The number of diploid individuals wi rh geno rype AiAjlcmd f j IIn AnWeinber g for This example mm 25 The 0 when and the numba expected 1mm Marxmm pmponims in lhe ma 0 Use aanxacT Tes r because expected number is less Thgn 5 for SS O oci occur on chro oso es linked ro o rher loci The fiTness of a single locus ripped from iTs inTeracTive conTexT is abouT as relevam To real problems of evoluTionary geneTics as The sTudy of The hmll L lll l4l Lu 1l Al Au4 1 u undersTanding of man39s sociopoliTical evoluTion Richard LewonTin quoTed in Hedrick 2005 Disequilibrium AES I imaTi on of LD is Cr39i39licGl for ALL Popma on genetic Two loci Two alleles gt Frequency of allele i of locus 1 is p i of locus 2 is 4 P1 A1 P2 A2 Genotype is written as AlBlAZBZ A1 B1 A2 32 Al and 31 are in coupling phase 9A1 and 32 are in re ulsion hose Easiest To Think about physically linked loci but not necessarily The case Meiosy 31 Bz A131 V Uha er Independenf Assor nenvf Independent Assortment 1 11 P1f11 With LD 9311 p1q1 D 3312 2 P142 D 1721 P2611 D CE22 192972 D 9312 P1Q2 Substituting from above table ltgt Can havg mga rivg gemoi ypz frequzvacies OMQXimum D say by aiigle fmqwencies 1 22 372 D Solution D39 DDmx mnsf 1k 1 Example if D is positive 39 5 47 5 Dm Calculation If D is posifive Dmx is M of Pm 0quot Pz h If D is negafive Dmx is lesser of PH 0quot PzCIz in This case OI is equivalent Shuffling of parental alleles during meiosis A lBlAZBZ ar Tially a function of physical rate for unlinked loci Where nr isquot number oflrepulsion phase gameifes and is number1M coupi219 phase gametes mbinafion rate a 39 E q a QC cquot r q J s 77 ltgt LJ2 E9U gepmmm mm M mam VU UQJS C FirsT genera rion gametes of offspring Second genera rion Genotypes Frequencies Al 32 A231 A2 B2 AlBlAIBI I31 3amp1 i A1BlA132 23313312 112312 111712 AIBZA1B2 9amp2 3amp2 23111 21 513115621 c is fhe r39 ecombii nafioh rate and Bails The initial amount 0sz Lb 111 9311 CD0 5512 5812 CDO 5621 1721 CD0 9322 22 CD0 x11CDOx22 CD0 x12 CD0X21CD0 V39Whe r39e 17 is fime iLn nemera l iions and e is bse of natural Jog O Decline in LB over39 Time wi rh different Theor39e rical recombination r39a res c 9 Even wi rh independen r segrega rion cO5 mul riple gener39a rions required To break up allelic associa rions 9 Genomewide linkage disequilibrium can be d by daemogir39aphic Tamar s more later Variation in recombination rate in The MHC region 333 human sperm donorst Recombination rate varies across chromosomes l n g l hf 26931 by locafi n rela veifd fgldm39er S39afld erifh 39in e39re chrumdsbrne39 66 39 dnf efrif V39SLeguenc39er polymdrphism vjand rejpejatc39drnpqslt 6 Highgsmha lpwgst e yeljs pdf 19 found ingggner i cghrggja ns r Pasman alcng chmmascme Mm HuTUF Eym gt 1 comm on enot ed 392ng 700 f9r y270 individuals 34 m illioriSNP gt 92 miiiio nLSNP in ftbfl39dl Human Haplofype Structure Lecture 26 Phylogeography Announcements U day our W fh materua A No quotV7 39339 N Urn7 FF C quota T r i L ltVgtFuma Egg5am omeso ayg Levee Come to review session on Friday it you39re wondering what that means gtLab 12 report due gtNo report required but 10 pt extra credit na g gtCourse evaluations httfpsesei wvuedu Last Time Quantitative genetics overview Types of variance gtHer39itability SNP associations tor coat color in mice Today Phylogenetics Undersfanding phylogenetic frees gtMajor39 approaches To determining Ll OPhylogeography introduction J7 5152 7 lt7 am by U y wu L 1 O 3 O O CH 39 u r 1 3 F 7 quot31 no b 3 mgcrug UUUEJUVUMMCCMSDC UJME O Ua 2 1 r O n 0 52902250753 QCJJQEJGQO 01 UZACCJQ QCBQUZEOCQEKFb 59303535 39 quotm mach W 01ng UE EgtU1y mg Wa 1 h p n 0quot I m Evolution Slide adap red from Mar ra Riu rar r nNltgtltglt c 4 mova What is a phylogeny nNltgtltglt c 4 mova Homology similarity that is the result of inheritance from a common ancestor Slide adapted from Marta Riutart Phylogenetic Tr39ee Terms Group cluster clade Leaves Operational Taxonomic Units OTUs terminal branches node interior gt branches ROOT Slide adap red from Mar ra Riu rar r Tree Topology Bacteria 1 Bacteria 2 Bacteria 3 Eukaryote 1 Eukaryote 2 Eukaryote 3 Eukaryote 4 Bacterial Bacteria2 Bacteria3Eukaryote1 EukaryoteZ Eukaryote3 Eukaryote4 Bacteria 1 Bacteria 2 Bacteria 3 Eukaryote 1 Eukaryote 2 tukarym 3 Eukaryote 4 Slide adapted from Marta Riutart AECDBF FBDCEA How abou r These Rooted versus Unrooted Trees archaea eukaryote h m 0 Unrooted tree archaea eukaryote eukaryote eukaryote KOOTed bacteria outgroup by outgroup archaea archaea Monophyletic group archaea eukaryote eukaryote Monophyletic group r00 eukaryote eukaryote Slide adapted from Marta Riutart Roofing with D as outgroup Slide adap red from Mar ra Riu rar r Now with C as outgroup JLLL quotIIE characTer39 s139a139e based Lowe Harris and Ash ron 2004 MANY possible Tr39ees can be buil r for a given se r of Taxa 4 m X m Unrooted Rooted 1 3 3 15 15 105 105 945 945 10395 10395 135135 135135 2027025 2027025 34459425 Lowe Harris and Ash ron 2004 Zn 5 R Zn 3 N 2quot3n 31 N 2quot2n 21 AKDOONCDWALU 2n 3U but global maxim um is here end up here If start here Um H A CU 3 4 O O 2 m e S n e B e F 7 my Viz 3C AM L Q Q 0 JD F r 4 U hr g L WU 9 rpm y m mu e W ngeneuw lt3 de jen m me W bl f mdeg EACFBD ECABDF ABCDEFG ABCDEFG ABCDEFG E AFDBC E ADFBC ECADFB Alternative trees W V W Number of times each partition of species is found AB 1 BCDF ACE 1 BDF ACEF BD AC BDEF AEF BCD ADEF BC ABDF EC ABCE DF p AIUVdb b UJUJ m Majority rule consensus tree of the unrooted trees 60 Felsens rem 2004 uences in eo r39a hic context 9 Can be used to infer39 evolutionary history of populations gt Migrations gt Population Subdivisions gt Bottlenecks Founder Effects lationships among populations gt Connectedness of populations gt Effects of39 land39sC ape39 features on gene flow Topology of Tree provides clues a ou r evolu rionary and ecological his rory of a se r of popula rions Dispersal crea res poor correspondence be rween geography and Tree Topology Q Vicariance division of popula rions preven ring gene flow among subpopula rions resul rs in nea r mapping of eora h on ro ha lo r39 es ltgt U WFDNA f 8 mduvuduca s ngm gd 233 thb ypch ltgt Pm mmy mg wwk n gvm s amdma hit PcaHQ msh pS thH c ypg of md We SH m Example Brown Bears Ursus arcfos A n J C a Q A j U10 lt1 U J gmd m CnD m 0 7s 395 N WU h mmw CE N a um qug h1p c yp m L W Europe ns YR tnj V E a an u u um U AW362004 American O MALE 4 Q arcfos ltgt DWQWSW bgggd 0 ngmgm ltgt Rgduggd diversify fem mam Q u f QHWQ KQd ka Vd WST gt e Studyarr39a 211 A SE Brown bears 39 00 738 056 m Mts 258 750 065 mks e 39296 765 0 0 Flathead R BO 650 071 E SIOPC 90 700 082 Paulatuk 116 575 038 lupp rrninc72 575 105 39 39 l x mcll4 458 160 V Slope 252 950 091 Newfoundland I 500 035 0761 0025 0755 0050 I 0670 0062 0650 0058 1605 00 3 1554 1081 0806 0017 0414 0055 9 A 39 o 5 pa 1 o 1 3 U o 3 o gt U 3 3 N O O 4 0 Degree of differeni ia fion r iven by disfances be i39ween islands Admiralfy much more diver qem fhan Chicago or Bar39cmo f 0 Less differen i ia on for nub LL m l4 39 i Ad 39 It markers 14739qu gt Why Lowe Harris and Ashton 2004 QAISQ rha 39equl Jinher i tanee Q f mi i o hoh dr igh 539h1q er e f ec ves o pglquiq n39size ofm i i oe di ldr ibn ltgt Mifb hond rionxis O39ne o39zus selec riiyeswe e psF s in Europe Q Highly degraded Form o low gene ric diversify Q Haplo rypes reveal 3 refugia during glaciation 6 Mi rafrion and admixture f0 owmg deglacla rlon su rure zonesquot m Scandmavua and cen rral Europe U arctos U2 U arctos U3 Taberle r e r al 1998 Molecular Ecology 7453 OWNS 1390 OM Ms M Africa and subse uem 39 migrwions Cavnl I irISLfor39rzaszDQS quotN afrur e GenicfiCS 331266 D39nllnnannnnhnl m39rDNA Q Mos r ancien r and diverse haplo rypes in Africa do rs Q Migra rion and admix rur39e is evnden r from presence of Alfrilican haplo rypes in o rher39 Q P ruva re dehydrogenase E1 a pha subuni r sequence Q 25 polymorphic si res 23 of which were in African sample 6 African 969 nonAfrican 9057 Q Using chimp sequence as oat rou39 es rima red Tha r divergence occurred 19 million years ago Haplotype A l l NonAfrican African Figure 1112 The maxirnum parsimony tree for the PDHAI gene for the sites given in Table 117 where the sites halving individual nmtatinns are indicated on the appropriate branches The resulting haplotypes are indicated at ends of the terminal branches after Harris and Hey 1991 enes show evidence of Asian or i in l 39 Sequence of XIinked ribonucleo ride reducfase M2 pseudogene 4 O Sugges rs single or igin model is Too simple admix rur e and selec rlon a Chlnlpanlee Human haplotypes haplotype A n c D E r G H Africa Asva n m j r 1219 H Ame To explain negative Tajima39s D in l2 l l kll A for RRMZP Balancmg selecTIon gt Bo r rleneckfou ndegr39 effect ed 500 000 SNP eno r as for 3 192 Euro cans 9 Used Principal Componen rs Analysis To ordina re samples in e OIndividuals assi ned To popula rions o origin wi rh high accuracy Lecture 20 Gene How and Parentage Analysis October 31 2008 Last Time 39 Fstatistics example 39 AMOVA 39 Fstatistics as inbreeding coefficients 39 Gene flow and drift 39 Gene flow and selection Today 39 More Fstatistics examples 39 Limitations of Fstats 39 Gene flow and LD 39 Paternity analysis 39 Individual Identity Announcements 39 Exam next Wednesday gtCovers everything from selection to gene flow today gtApproximately the same format as Exam 1 gtSee sample exam 2 from last year 39 Review session on Monday gtPlease come with queSTIons or endure a boring onSIaugnT of slides again 39 Vote gtEarly voting today and tomorrow at former WalMart Mountaineer Mall Greenbag Road FST is related 39I39o life history Seed Dispersal Gravity 0446 Exl losivecal sule 0262 WingedPlumose 0079 Successional Stage Early 0411 Middle 0184 Late 0105 Life Cycle Annual 0430 Shortlived 0262 Longlived 0077 Loveless and Hamrick 1984 Salamander Population Structure Stream salamanders almost exclusively aquatic move mostly upstream Hypothesized that steepness of stream inhibits migration between populations Pairwise genetic differentiation of sites was positively correlated with e stream steepness 000 Stream Steepness Lowe et a1 2006 Ecology 87334 7 Gyranophilus porphyriticus Polar Bear Population Structure Need accurate measures of population connectedness for setting sustainable native hunting limits Sampled 19 populations from throughout range using microsatellites Island populations more isolated Differentiation very low gt Pairwise F570004 to 010 gt Nm as high as 89 r Ecology 1990 8 15714584 FN 5V EG Genetic Distances it Not Measured 7 Zero Small Intermedlate Lar H E 39 A 39Paetkau et 51 1999quot Why might markers with high mutation rates result in overestimate of Nm 2 1 m2 ST 2N 2N 11 m2 Mutation and Population structure Estimates High mutation rates 1 91372005 H imam cause depression in Fsr 657 estimates H H G57 T S T H GST 1H lt1Hs HednckZElElS Maximum differentiation determined by average homozygosity of subpopulations Corrected Estimate of F51 Scale estimates based on the maximum value possible I For k subpopulations assuming no shared alleles It i 2 l 392 l 1 39 P1quot239 39P52 H1 111mg 1 k A 3939 G HTmaX HS 639 2 GST STMax ST G H TmaX ST max Rescales srfrom O to 1 Correction must be made for all comparisons among studies Example Papaus frchocarpa Population Structure gt500 genotypes collected at over 140 locations in northern art of rane Allozymes in 10 populations in Oreon and Washinton Drastic underestimate of 0 ulation structure b GST Gilchrist et al 2006 Molecular Ecology No of GST GST populations GST HS max adj 88R Abdelhameed amp ElKassaby unpublished 16 085 014 m Allozymes VVeberampStettler1981 10 006 009 09 007 Limitations of PST FST is a long integrated look into the evolutionaryecological history of a population may not represent sfafus qua Assumptions of the model frequently violated gtIsland model unrealistic gtelection is often an important factor gt Mutation may not be negligible gt Sam lin error Alternatives to PST Direct measurements of movement mark recapture Genetic structure of paternal and maternal gametes only gtChloroplast and mitochondrial DNA gt Pollen gametes Parentage analysis direct determination of the parents of particular offspring through DNA fingerprinting Parenfage Analysis Direc rly es rima re r39eal Time gene flow Different approaches depending on goals and configura rion of sysTem Need increasingly polymorphic markers depending on approach gt unique allele lt pa rer39ni ry lt maTer39nITy lt par39enTage a Unique allele analysis Focal offspring Lowe Harris and Ash ron 2004 Paternity Exclusion Analysis Defermine mul rilocus geno rypes of all mo rhers offspring and po ren rial fa rhers Defermine pa rernal game re by sub rrac ring ma rernal geno rype from rha r of each offspring Infer pa rerni ry by comparing rhe mul ri locus geno rype of all game res ro Those of all po ren rial males in The popula rion Assign pa rerni ry if all po ren rial males excep r one can be excluded on The basis of gene ric incompa ribili ry wi rh The observed pollen game re geno rype Unsampled males mus r be considered Sweet Simulation of Paternity Analysis Collected seeds baby from a hermaphroditic selfincompatible plant I Which of the candidate hermaphrodites you fathered the seeds Six loci with varying numbers of alleles 1 Organize candy into loci next slide 2 Determine paternal contribution to offspring by subtracting maternal alleles 3 Exclude potential fathers that don39t have paternal allele 4 Nonexcluded candidate is the father wa excluding re V Wildberty Skittles notice 77 Chocolate mampm S notice m Peanut mampm s Red Runts PaTerniTy Exclusion I Fir39sT sTep is To deTermine Low paTernal conTribuTion based on seedling alleles ThaT do noT maTch moTher gt NoTice for locus 3 boTh alleles maTch moTher so There are Two poTenTial paTernal conTr ibuTions I Male 3 is The puTaTive faTher39 because he is The only one ThaT maTches paTernal conTr ibuTions aT all loci Locus 2 Locus 3 Seedling Mulher Malel MaleZ Male Mailed Male No We YES YES YES YES g Paternity Exclusion Analysis Possible outcomes Only one male canno r be excluded 39 More Than one male canno r be excluded All males are excluded Consequences Pa rer39ni ry is assigned Analyze mor39e loci Conclude There is pollen migra rion from exTernal sources Probabilities of Pa rerni ry Exclusion Single Locus 2 alleles codominan r I The paTerniTy exclusion probabiliTy is The Sum of The probabili ry of all exclusionary combinaTions Excluded paternity Probability of M other O spring types exclusion 41A1p 441mm 442442903 pip Al A2 102 Al Al F 1311132 AlAg2p1p2 A1A1p12 44242 pip Al A2 0 2 A2A2P22 AlA Pil 101132 AQAQ 141A2p1 AEAZ plp gE A2A2P2 A1A1P Pip l Sum Prk p1p21 p1p2 ProbabiliTy of a faISely accu3ed male of noT m Pr 1 H1 Prk k1 maTching for aT leasT one of m loci See Chakrabor ry e r al 1988 Gene rics 118527 for a more general calcula rion of exclusion power Alleles ver39sus Loci For39 a given number of alleles one locus wi rh man alleles r39ovides mor39e exclusion power39 Than many loci wi rh few alleles gt10 loci 2 alleles Pr39 0875 gt1 locus 20 alleles Pr39O898 I Even allele frequencies provide more power39 Characteristics of an ideal genetic marker for A aternit anal sis Highly polymorphic ie wi rh man alleles39 Codominan r Reliable Low cos r Easy To use for39 geno ryping large numbers of individuals Mendelian or39 pa rer39nal inher39i rance Who r Type of informo rion can we gef from po rer39nl ry onolysus I Dis rr39ibu rion of migr39o rion dis ronces Example of two I Foc ror39s offec ring mole 04 h I r39epr39oduc rive success t 99mm and mo ring po r rer39ns 03 dlsmbumns of pollen migration Frequency synchrony of flowering or39 es rr39us size Ioco rion wind direction e rc distances 01 39 Realized gene TIOW U39IOT Chly dispersal in 0 500 1000 1500 2000 2500 3000 currenf genera on Pollen migration distance m


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