Download Genetics(Semester(One,(Year(Two!

Genetics(Semester(One,(Year(Two!
Need$genetic$variation$
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Natural$
o Monogenic$
o Polygenic$
Induced$
o Mutagenesis$
Variation$between$organisms$
1. Phenotypic$
a. Morphological$
b. Sterile$
c. Lethal$
2. Molecular$
a. Biochemical$(enzymes,$hormones$etc)$
b. DNA$
c. Proteins$
Types&of&alleles&
1.
2.
3.
4.
5.
6.
Wild$type$–$dominant$phenotype$(normal)$
Hypomorphic$mutant$–$defective$phenotype,$still$partially$effective$
Amorphic$mutant$–$loss$of$function,$extreme$change$
Hypermorphic$mutant$–$increase$of$function,$more$efficient$
Neomorphic$mutant$–$gain$of$function,$new/different$function$
Antimorphic$mutant$(dominant$negative$mutation)$–$altered$function,$antagonistic$to$wild$type.$Works$
against$wild$type$protein.$
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7. Conditional$mutant$–$different$under$certain$conditions$e.g.$temperature$sensitive$mutant$
Penetrance&
Mutant$allele$in$genetic$background,$depending$on$the$number$of$mutants$or$how$many$genes$are$interacting$the$
presence$of$mutations$may$have$varied$effects$
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Example$One$
o Wild$type$–$B,$C$
o Mutant$–$A$
o Slightly$abnormal$phenotype$
$Example$Two$
o Wild$type$–$B$
o Mutant$–$A,$C$
o Significantly$abnormal$phenotype$
Mutant$alleles$do$not$have$to$express$phenotype,$can$be$affected$by$gene$interaction$(penetrance,$degree$of$
expression)$
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Dominance&
Only$one$copy$of$allele$needed$to$produce$phenotype$
Dominant$allele$phenotype$may$have$partial$or$total$gene$product$from$dominant$allele$
E.g.$AA:$100%$dominant,$Aa:$50%$dominant$50%$recessive.$But$both$express$dominant$phenotype$
Haploinsufficiency:$May$need$100%$gene$product$to$express$phenotype.$If$heterozygous,$not$enough$gene$product$
of$recessive$allele$so$expresses$dominant$phenotype.$
A$hypermorphic/neomorphic$allele$may$lead$to$homozygous$extreme$mutant$compared$to$the$heterozygous.$
Amorphic$mutation:$Loss$of$function,$usually$recessive$
Antimorphic$mutation/Neomorphic$mutation:$Usually$dominant$
Codominance:$Heterozygous$expresses$phenotype$of$both$homozygotes$e.g$blood$antigens$
Incomplete$Dominance:$Heterozygous$has$intermediate$phenotype$e.g.$flower$colours$$$
Mutant$alleles$may$show$a$dominant$phenotype$when$heterozygous$but$a$different$(recessive)$phenotype$when$
homozygous.$This$is$due$to$gene$product$interactions.$Heterozygous$means$two$different$gene$products$may$affect$
each$other,$homozygous$is$only$one$gene$product$(may$give$different$phenotype)$
At$the$DNA$sequence$level$all$alleles$are$co\dominant.$At$a$molecular$level,$protein$production$sequence.$
Variations$in$the$DNA$sequence$produce$equal$amounts$of$protein,$no$dominance.$$
Whether$an$allele$shows$dominance$or$not$depends$on$which$aspect$of$the$phenotype$you$are$studying.$
The$phenotype$(morphological$variation)$not$the$allele$is$dominant$or$recessive.$
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Mendel’s&Laws&
1. Alleles$will$always$segregate$away$from$each$other$into$gametes.$Aa$allele$to$A$+$a$gamete$contribution$
2. Alleles$of$separate$genes$will$always$segregate$independently$into$gametes.$
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!!
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×
×
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= 9: 3: 3: 1!!ℎ!"#$%&!!!"#$%.$
= 1: 1: 1: 1!!ℎ!"#$%&!!!"#$%$
Chromosome&Theory&
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#$of$phenotypes$is$exponential,$#$of$heritable$factors$exceeds$the$#$of$chromosomes$
Therefore$expect$multiple$factors$to$exist$per$chromosome$
Predict$that$factors$on$the$same$chromosome$will$be$transmitted$as$a$block$
Therefore$factors$on$the$same$chromosome$will$not$assort$independently$
Test&cross&of&Drosophila&
Recombinant:$new$genotype$
Combinant:$parental$genotype$
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Two$traits,$red/purple$eyes$and$normal/vestigial$wings$
Parents:$Homozygous$wild$type$x$homozygous$recessive$
F1:$Heterozygous$wild$type$
F1$crossed$with$homozygous$recessive$(test$cross)$
o
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!" ! !"!
!" !"
×
!" !"
!" !"
$$
o F1$produces$>1$type$of$gamete,$tester$produces$only$1$type$of$gamete$
Mendel$would$predict$equal$proportions$of$F1$gametes$(!" ! !"! , !"!!", !" ! !", !"!"! )!$due$to$
independent$assortment,$thus$giving$equal$proportion$of$phenotypes$
Chromosome$theory$would$predict$equal$proportions$if$gene$loci$were$on$different$chromosomes$or$only$
combinants$if$they$were$on$the$same$chromosome$
Observed$presence$of$all$four$phenotypes$with$ratio’s$heavily$stacked$to$parental$phenotypes.$$
(Phenotypes$not$genotypes)$
Ab$and$aB$would$be$parentals$
AB$and$ab$would$be$recombinants$
BUT$we$only$know$that$the$ab$phenotypes$are$recombinants$for$sure$(AB$phenotypes$may$have$aB,$Ab,$or$AB$
gametes)$
The$frequency$of$the$ab$phenotypes$is$the$probability$of$the$ab$gametes$squared.$(Pr !"× Pr !")$
Therefore$frequency$of$ab$gametes$is$square$root$of$0.01$=$0.1$
Frequency$of$the$other$possible$recombinant$AB$is$equal$in$frequency$as$when$making$ab,$AB$is$made$as$well.$$
Recombination$frequency$=
(!.!!!.!)
!.!
= 0.2 = 20% = 20!!"!(!"#!!"#$%)$
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Physical&Linkage&vs&Genetic&Linkage&
Genes$are$linked$if$0%<RF<50%$
0% ≤ !"#$%&'()*'$(!!"#$%#&'( ≤ 50%$
If$genes$are$far$apart$on$the$same$chromosome,$they$might$independently$assort$
To$show$linkage$for$genes$located$far$apart$(RF$~$50%)$we$can$$
1. Take$advantage$of$achiasmatic$gametogenesis$
2. Find$a$third$gene$in$the$middle$
Frequencies$of$crossing$over$is$proportional$to$distance$between$genes$
Can$combine$data$from$different$experiments$to$form$a$chromosome$map$
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Can$be$re\organised$into$
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Can$also$build$a$chromosome$map$by$combining$multiple$two$factor$crosses.$But$less$accurate$because$may$miss$$
double$recombinations$$
Look$at$the$largest$map$distance,$the$two$genes$involved$will$be$the$first$and$last$in$the$gene$order$
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Genome&maps&
Allow$the$tracking$of$chromosome$segments.$$
Know$where$to$look$for$certain$defects$
Limitations#of#phenotypic#markers#
1.
2.
3.
4.
Phenotypic$mutants$are$rare$
Differences$are$not$always$clear$cut$
Multiple$genes$may$affect$one$phenotypes$
The$need$to$maintain$mutant$stocks$is$expensive$
Molecular#markers#
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DNA$
o Differences$in$DNA$sequence$
o Differences$in$charge$of$proteins$
Both$phenotypic$and$molecular$tag$and$track$chromosome$transmission$
Scored$by$chemical$assays$$
Benefits#of#Molecular#markers#
1. Abundant$
2. Random$distribution$
a. Provides$genome$wide$coverage$
3. Many$markers$can$be$scored$(genotyped)$in$a$single$cross$
4. Genotyping$can$be$automated$and$streamlined$
Markers:$Polymorphism$+$Detection$method$
Polymorphisms$
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Nucleotide$substitution$
o Single$nucleotide$polymorphism$(SNP)$
Insertion/deletion$
Expansion/contraction$
Microsatellites$$
o Base$sequence$repetitions$$
Detection$methods$
Phage&Genetics&
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Phage$are$haploid$$
o Phenotype$will$equal$genotype$
No$nuclei,$do$not$undergo$mitosis$or$meiosis$
Undergo$recombination$and$complementation$
Have$genetic$variation$
Phage#Genetic#Variation#
1. Unconditional$Mutants$
a. Plaque$morphology$mutants$
i. Clear$plaque$mutants$
ii. Lysogen$negative$mutants$
2. Conditional$Mutants$
a. Grow$in$one$set$of$conditions$known$as$the$permissive$conditions$
b. Will$not$grow$under$non\permissive/restrictive$conditions$
c. Temperature$sensitive$mutants$
d. Host$range$specific$mutants$
Plaque#morphology#mutants#
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λ$phage$that$have$lost$the$ability$to$form$lysogens$(always$undergo$lytic$cycle)$
$Show$plaques$that$do$not$have$any$lysogens$growing$in$them.$Always$clear$
Rapid$lysis$(r_$)mutants$of$phage$T4$
Temperature#sensitive#mutants#
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E.g.$grow$at$37$degrees$but$not$at$42$degrees$
Host#range#mutants#
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E.g$Unable$to$grow$on$certain$strains$of$E.Coli$
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Recombination&in&phage$
1. Co\infection$of$host$cell$with$multiple$phages.$
a. Single$bacteria$infected$with$multiple$mutations$
2. Co\infection$creates$‘diploid$state’$for$the$phage$
3. Recombination$event$occurs$between$two$phage$DNA$molecules$with$different$mutations$
4. Two$distinct$phage$DNA$molecules$are$created,$different$from$the$parentals$
5. The$progeny$will$have$different$genotypes$than$the$parents$
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