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EXTENSIONS OF MENDELIAN GENETICS EXTENSIONS OF MENDELIAN GENETICS

EXTENSIONS OF MENDELIAN GENETICS EXTENSIONS OF MENDELIAN GENETICS

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EXTENSIONS OF MENDELIAN GENETICSEXTENSIONS OF MENDELIAN GENETICS

• What happens when What happens when inheritance doesn’t follow the inheritance doesn’t follow the patterns observed by Mendel?patterns observed by Mendel?

• There are many reasons why There are many reasons why traits might deviate from traits might deviate from expected. expected.

Main ConceptsMain Concepts

•Alleles Alter Phenotypes in Alleles Alter Phenotypes in Different WaysDifferent Ways

•Incomplete DominanceIncomplete Dominance•CodominanceCodominance•Multiple Alleles Multiple Alleles •Lethal Alleles Lethal Alleles •Phenotypes Often Affected by More Phenotypes Often Affected by More Than One Gene (Polygenic)Than One Gene (Polygenic)•A Single Gene May Have Multiple A Single Gene May Have Multiple Effects (Pleiotropy)Effects (Pleiotropy)•Sex Linked TraitsSex Linked Traits•Sex-Limited and Sex-Influenced Sex-Limited and Sex-Influenced InheritanceInheritance

• How are alleles formed?How are alleles formed?• MUTATIONMUTATION

• Wild-type allele:Wild-type allele: occurs most occurs most frequently in nature and is frequently in nature and is usually dominantusually dominant

• Different types of mutations Different types of mutations can alter alleles (or produce can alter alleles (or produce new ones)new ones)

MutationsMutations• Loss of function mutation: Loss of function mutation: a a

mutation that causes the mutation that causes the reduction/loss of the specific reduction/loss of the specific wild-type functionwild-type function

• If the loss is complete, the If the loss is complete, the mutation has resulted in what mutation has resulted in what is called a is called a null allelenull allele

• Gain of function mutation: Gain of function mutation: a a mutation that enhances the mutation that enhances the function of the wild-type allelefunction of the wild-type allele

Incomplete DominanceIncomplete Dominance• Incomplete dominance – Incomplete dominance –

heterozygotes show a distinct heterozygotes show a distinct intermediate phenotype intermediate phenotype different from homozygous different from homozygous genotypesgenotypes

• Neither trait is dominantNeither trait is dominant

SymbolsSymbols• Alleles that are incompletely Alleles that are incompletely

dominant are written using a dominant are written using a superscript letter.superscript letter.

• Flower color:Flower color:• CCWWCCWW (white) plant X C (white) plant X CRRCCRR (red) (red)

plant will produce all Cplant will produce all CRRCCWW offspringoffspring

• Are these traits blended?Are these traits blended?• NO … the alleles are particulate NO … the alleles are particulate

(they remain separate and do not (they remain separate and do not influence each other).influence each other).

• How do we know?How do we know?• A cross of two pink individuals A cross of two pink individuals

will produce red, white and pink will produce red, white and pink individuals. individuals.

• The phenotypic ratio will be The phenotypic ratio will be 1:2:1, like the genotypic ratio1:2:1, like the genotypic ratio

Figure 4-1 Copyright © 2006 Pearson Prentice Hall, Inc.

Incomplete DominanceIncomplete Dominance

• What is really going on?What is really going on?• White allele is most likely a “loss White allele is most likely a “loss

of function” mutationof function” mutation• Wild type (red) “codes” for Wild type (red) “codes” for

synthesis of red pigmentsynthesis of red pigment• Mutant allele (white) cannot Mutant allele (white) cannot

synthesize the pigmentsynthesize the pigment• Therefore, the heterozygote only Therefore, the heterozygote only

produces ½ the amount of produces ½ the amount of pigment (pink)pigment (pink)

• True incomplete dominance is True incomplete dominance is rarerare

• Individuals may appear Individuals may appear completely dominant until completely dominant until viewed at the molecular levelviewed at the molecular level

• Tay-Sachs diseaseTay-Sachs disease• Homozygous recessive = severely Homozygous recessive = severely

affected, death before age 3affected, death before age 3• Heterozygotes appear normal, but Heterozygotes appear normal, but

only produce about 50% of normal only produce about 50% of normal enzymesenzymes

• Threshold effectThreshold effect

• The threshold effectThe threshold effect - normal - normal phenotypic expression occurs phenotypic expression occurs whenever a certain level (≤ whenever a certain level (≤ 50%) of gene product is 50%) of gene product is attained.attained.

CodominanceCodominance• Codominance – 2 alleles affect Codominance – 2 alleles affect

the phenotype in separate, the phenotype in separate, distinguishable waysdistinguishable ways

• Alleles for curly hair and Alleles for curly hair and straight hair are codominantstraight hair are codominant

• Curly hair = homozygous for Curly hair = homozygous for curly hair allelescurly hair alleles

• Straight hair = homozygous for Straight hair = homozygous for straight hair allelesstraight hair alleles

• Heterozygous individuals have Heterozygous individuals have wavy hairwavy hair

Incomplete Dominance vs. Incomplete Dominance vs. CodominanceCodominance

• With incomplete dominance we get With incomplete dominance we get a a reduced functionreduced function of the dominant of the dominant trait (due to recessive), so that the trait (due to recessive), so that the third phenotype is something in the third phenotype is something in the middle (red x white = pink). middle (red x white = pink).

• In codominance, the "recessive" & In codominance, the "recessive" & "dominant" traits appear "dominant" traits appear togethertogether in the phenotype of hybrid in the phenotype of hybrid organisms – appears to be a organisms – appears to be a ““blendblend””

Dominance = common?Dominance = common?

• PolydactylyPolydactyly – – an allele that an allele that is dominant to is dominant to the recessive the recessive allele for 5 allele for 5 digitsdigits

• Recessive Recessive allele more allele more common – common – 99% have 5 99% have 5 digitsdigits

Multiple AllelesMultiple Alleles• Can only be studied in Can only be studied in

populationspopulations• WHY?WHY?• Because individuals can only Because individuals can only

have 2 alleles for a gene!have 2 alleles for a gene!• Example of trait covered by Example of trait covered by

multiple alleles?multiple alleles?• Human Blood TypeHuman Blood Type

• ABO antigensABO antigens

• ABO blood groups in humans ABO blood groups in humans are determined by three are determined by three alleles, alleles, IIAA, , IIBB, and , and IIOO (also (also referred to as referred to as ii))• Both the Both the IIAA and and IIBB alleles are alleles are

dominant to the dominant to the IIOO allele allele • The The IIAA and and IIBB alleles are alleles are

codominant to each othercodominant to each other

• I I stands for “isoagglutinogen”, stands for “isoagglutinogen”, which is another word for which is another word for antigen. antigen.

How many blood types are How many blood types are possible?possible?

• Because each individual Because each individual carries two alleles, there are carries two alleles, there are six possible genotypes and six possible genotypes and four possible blood typesfour possible blood types• IIA A IIAA or or IIAAIIOO- type A- type A• IIB B IIBB or or IIBBIIOO- type B- type B• IIA A IIBB - type AB - type AB• IIOOIIOO - type O - type O

Table 4-1 Copyright © 2006 Pearson Prentice Hall, Inc.

• The blood types differ due to The blood types differ due to the molecules that are present the molecules that are present on the outside of RBC on the outside of RBC (antigens)(antigens)

Lethal AllelesLethal Alleles• Loss of function mutationLoss of function mutation

• Can (sometimes) be tolerated in Can (sometimes) be tolerated in heterozygous state heterozygous state

• Can have a mutant phenotype Can have a mutant phenotype (acts dominant) when (acts dominant) when heterozygousheterozygous

• BUTBUT…… may be lethal in the may be lethal in the homozygous statehomozygous state

yy

Figure 4-4 Copyright © 2006 Pearson Prentice Hall, Inc.

Lethal allelesLethal alleles• In some cases, the lethal allele In some cases, the lethal allele

is DOMINANT, so even is DOMINANT, so even heterozygotes will die. heterozygotes will die.

• Why does this allele persist in Why does this allele persist in the population?the population?• Late acting (Huntington’s)Late acting (Huntington’s)• Individuals reproduce before Individuals reproduce before

allele takes affectallele takes affect

Polygenic TraitsPolygenic Traits• Many traits with a distinct Many traits with a distinct

phenotype are affected by phenotype are affected by more than one gene more than one gene

• The cellular function of The cellular function of numerous gene products numerous gene products contributes to the contributes to the development of a common development of a common phenotypephenotype• Ex - skin color in humans is Ex - skin color in humans is

controlled by at least 3 controlled by at least 3 different genesdifferent genes

• Imagine - each gene has 2 Imagine - each gene has 2 alleles, (light/dark), alleles, (light/dark), demonstrate incomplete demonstrate incomplete dominancedominance

• AABBCCAABBCC (dark) and (dark) and aabbccaabbcc (light)(light)

• Cross between 2 Cross between 2 AaBbCcAaBbCc (intermediate) produces wide (intermediate) produces wide range of shadesrange of shades

Epistasis Epistasis • EpistasisEpistasis -- a gene at one locus a gene at one locus

alters the phenotypic alters the phenotypic expression of a gene at a expression of a gene at a second locussecond locus

• One gene can mask the effect One gene can mask the effect of the other gene of the other gene

• Two gene pairs can Two gene pairs can complement each other, such complement each other, such that one dominant allele is that one dominant allele is required at each locus to required at each locus to express a certain phenotypeexpress a certain phenotype

Epistasis exampleEpistasis example• Mice (and many other mammals) - Mice (and many other mammals) -

coat color depends on two genescoat color depends on two genes• One (One (epistatic epistatic gene), determines gene), determines

whether pigment will be deposited in whether pigment will be deposited in hairhair• Presence (Presence (CC) is dominant to absence () is dominant to absence (cc))

• Second determines whether pigment Second determines whether pigment deposited is black (deposited is black (BB) or brown () or brown (bb))• The black allele is dominant to the The black allele is dominant to the

brown allelebrown allele

• Individual with Individual with cccc has a white has a white ((albinoalbino) coat regardless of the ) coat regardless of the genotype of the 2nd genegenotype of the 2nd gene

Epistasis – more complexEpistasis – more complex• In cats (and other mammals), a In cats (and other mammals), a

pattern of hair termed “pattern of hair termed “agoutiagouti” ” is an example of epistasisis an example of epistasis

• Some cats have hairs in which Some cats have hairs in which there is more than one color there is more than one color distributed along the hair shaft distributed along the hair shaft (banded – agouti)(banded – agouti)

• Agouti fur color is typical of Agouti fur color is typical of many wild animals such as mice many wild animals such as mice squirrels and rabbits – good for squirrels and rabbits – good for camouflage!camouflage!

• Agouti is determined by the Agouti is determined by the dominant dominant agoutiagouti allele, allele, AA

• Hairs on non-agouti cats are Hairs on non-agouti cats are unbanded, producing a solidly unbanded, producing a solidly colored coatcolored coat

• Such a cat is homozygous for Such a cat is homozygous for the the non-agoutinon-agouti allele ( allele (aaaa) at ) at the the agoutiagouti locus locus

• Again – regardless of color. SO Again – regardless of color. SO … you could have an agouti … you could have an agouti brown, agouti black, etc. brown, agouti black, etc.

Epistasis RatiosEpistasis Ratios• When studying a single When studying a single

characteristic, a ratio characteristic, a ratio expressed in 16 parts (e.g., expressed in 16 parts (e.g., 3:6:3:4) suggests that 3:6:3:4) suggests that epistasis is occurring.epistasis is occurring.

PleiotropyPleiotropy• Pleiotropy occurs when Pleiotropy occurs when

expression of a expression of a single genesingle gene has multiple phenotypic has multiple phenotypic effects, and it is quite commoneffects, and it is quite common

• For example, the wide-ranging For example, the wide-ranging symptoms of sickle-cell symptoms of sickle-cell disease are due to a single disease are due to a single genegene

• Marfan syndromeMarfan syndrome• What US president What US president

may have had may have had Marfan?Marfan?

The EnvironmentThe Environment• Phenotype is not always a Phenotype is not always a

direct expression of genotypedirect expression of genotype• The environment plays a role The environment plays a role

in a gene’s expression. in a gene’s expression.

Environmental MutationsEnvironmental Mutations• Conditional or temperature-Conditional or temperature-

sensitive mutations sensitive mutations - mutations - mutations affected by temperatureaffected by temperature• useful in studying mutations that useful in studying mutations that

affect essential processesaffect essential processes

• Nutritional mutationsNutritional mutations – – mutations affected by dietmutations affected by diet• may prevent phenotype from may prevent phenotype from

reflecting genotype. Ex -mutations reflecting genotype. Ex -mutations in a biosynthetic pathwayin a biosynthetic pathway

X-linked or Sex linked traitsX-linked or Sex linked traits• Genes are located on the X Genes are located on the X

chromosomechromosome• Present a unique pattern of Present a unique pattern of

inheritance due to the inheritance due to the presence of only one X presence of only one X chromosome in maleschromosome in males

• Females (XX) can be Females (XX) can be heterozygous (carriers), while heterozygous (carriers), while their sons (XY) can express the their sons (XY) can express the disease/trait. disease/trait.

• DrosophilaDrosophila (fruit fly) eye color (fruit fly) eye color was one of the first examples was one of the first examples of X-linkage describedof X-linkage described

• DrosophilaDrosophila was a favorite was a favorite model organism for model organism for Thomas Thomas Hunt MorganHunt Morgan

• Morgan studied eye color in Morgan studied eye color in fruit flies – the trait did not fruit flies – the trait did not have normal Mendelian ratioshave normal Mendelian ratios

• Crosses of white-eyed male Crosses of white-eyed male with a red-eyed female - all Fwith a red-eyed female - all F11 offspring had red eyesoffspring had red eyes• The red allele appeared dominant The red allele appeared dominant

• Crosses between FCrosses between F11 produced produced classic 3:1 ratio classic 3:1 ratio

• SurprisinglySurprisingly, the white-eyed , the white-eyed trait appeared only in malestrait appeared only in males• All the females and half the All the females and half the

males had red eyesmales had red eyes• Morgan concluded that a fly’s Morgan concluded that a fly’s

eye color was linked to its sexeye color was linked to its sex

Figure 4-11 Copyright © 2006 Pearson Prentice Hall, Inc.

Figure 4-12 Copyright © 2006 Pearson Prentice Hall, Inc.

pp

Table 4-3 Copyright © 2006 Pearson Prentice Hall, Inc.

• Lethal X-linked recessive Lethal X-linked recessive disorders are observed only in disorders are observed only in males, since females can only males, since females can only be heterozygous carriers that be heterozygous carriers that do not develop the disorders.do not develop the disorders.