Unit 3 -Inheritance II

Extending Mendelian Genetics

Extending Mendelian Genetics

Inheritance patterns are often more complex than predicted by simple Mendelian genetics

The relationship between genotype and phenotype is rarely simple

There are some traits which are not inherited following Mendelian principles

These special cases include:

1. Codominance/Incomplete dominance/Partial dominance

2. Multiple alleles3. Pleiotropy4. Gene interaction5. Epistasis6. Phenotypes and environment7. Quantitative characters/Polygenic inheritance8. Linkage/autosomal linkage/linked genes9. Sex linkage10. X-chromosome inactivation11. Lethal genes

Extending Mendelian Genetics for a Single Gene

The inheritance of characters by a single geneMay deviate from simple Mendelian patterns

Incomplete Dominance/Codominance Complete dominance Occurs when the phenotypes of the heterozygote and dominant homozygote are

identical. Eg. In Mendel’s pea plants In codominance/incomplete dominance Neither of the alleles of the genes is completely dominant and the F1 hybrids have

a phenotype somewhere between those of the two parental varieties. Example of codominance:

1. Flower colour in Snapdragons

2. The human blood group MN

In incomplete dominance The phenotype of F1 hybrids is somewhere between

the phenotypes of the two parental varieties

P Generation

F1 Generation

F2 Generation

RedCRCR

Gametes CR CW

WhiteCWCW

PinkCRCW

Sperm

CR

CR

CR

Cw

CR

CRGametes1⁄2 1⁄2

1⁄2

1⁄2

1⁄2

Eggs1⁄2

CR CR CR CW

CW CWCR CW

The third phenotype (pink flowers) in the F1 generation results from flowers of the these heterozygotes having less red pigment that the red homozygotes as there is only one red-flower allele which produces pigment colour.

Interbreeding the F1 hybrids produces F2 offspring with a phenotypic ratio of 1 red: 2 pink: 1 white.

The segregation of the red-flower and white-flower alleles in the gametes produced by the pink-flowered plants confirms that the alleles for flower colour are heritable factors that are inherited as discrete alleles.

Another example – the human MN blood group The human MN blood group is determined by co

dominant alleles for two specific molecules located on the surface of red blood cells, the M and N molecules.

Individuals homozygous for the M allele have red blood cells with only M molecules; individuals homozygous for the N allele have red blood cells with only N molecules; but both M and N molecules are present on the red blood cells of those that are heterozygous, MN.

Multiple Alleles

The ABO blood group in humans Is determined

by multiple alleles

Pleiotropy

In pleiotropy A gene has multiple phenotypic effects Example: In his studies of a gene that influenced flower colour in garden peas, Mendel noted that the purple flower trait

was dominant to white. However, he also observed that plants with purple flowers always had reddish stems and grey seed coats and those with white flowers always had green stems and white seed coats. He proposed that the gene for flower colour also influenced the colour of the stem and seed coat.

Extending Mendelian Genetics for Two or More Genes Some traits

May be determined by two or more genes

Gene Interaction

Alleles of more than one gene affect each other

Example – comb shape in fowls

Epistasis

A different type of interaction between genes occurs if the phenotype controlled by one gene masks that of the other gene.

In epistasis A gene at one locus alters the phenotypic expression of a gene at a second locus Eg. Coat colour in mice – The gene for pigment deposition (C/c) is epistatic to the

gene that codes for black or brown pigment.

Because of epistasis, the phenotypic ratio of the F2 offspring becomes 9 black: 3 brown: 4 white which is the modified ratio of Mendel’s dihybrid crosses which give 9:3:3:1.

B - black b – brown C - allows pigment

deposition either black/brown

c – no pigment deposited hence white

BC bC Bc bc1⁄41⁄41⁄41⁄4

BC

bC

Bc

bc

1⁄4

1⁄4

1⁄4

1⁄4

BBCc BbCc BBcc Bbcc

Bbcc bbccbbCcBbCc

BbCC bbCC BbCc bbCc

BBCC BbCC BBCc BbCc

9⁄163⁄16

4⁄16

BbCc BbCc

Sperm

Eggs

Nature and Nurture: The Environmental Impact on Phenotype

Another departure from simple Mendelian genetics arises When the phenotype for a character depends on environment as well

as on genotype Examples:

1. Coat colour of Siamese cats

2. Flower colour for Hydrangea

3. Colour of the flamingo

4. Phenylketouria mutation in humans

The norm of reaction Is the phenotypic range of a particular

genotype that is influenced by the environment

Acidic soil

Alkaline soil

Multifactorial characters Are those that are influenced by both genetic and

environmental factors Many human diseases

Have both genetic and environment components Examples include

Heart disease and cancer

Quantitative and Qualitative characters Qualitative characters – individuals can be

grouped into distinct phenotypic classes. Example – seed colour, yellow or green Qualitative characters are controlled by

single genes and show discontinuous variation

Quantitative characters Quantitative characters exhibit continuous variation

and phenotype is measured along a continuous scale as the differences are not clear-cut.

Quantitative characters are influenced by the combined action of a number of genes, each of which produce a small effect.

Example – human height and weight, grain colour in wheat

These characters are polygenic characters and may also be influenced by the environment

Linkage

Autosomal linkage Sex linkage

Locating Genes on Chromosomes Genes Are located on chromosomes Can be visualized using certain techniques Mendelian inheritance has its physical basis in the behavior of chromosomes Several researchers proposed in the early 1900s that genes are located on chromosomes The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

How linkage was established

The chromosome theory of inheritance states thatMendelian genes have specific loci on

chromosomesChromosomes undergo segregation and

independent assortment

The chromosomal basis of Mendel’s laws

Yellow-roundseeds (YYRR)

Green-wrinkledseeds (yyrr)

Meiosis

Fertilization

Gametes

All F1 plants produceyellow-round seeds (YyRr)

P Generation

F1 Generation

Meiosis

Two equallyprobable

arrangementsof chromosomesat metaphase I

LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT

Anaphase I

Metaphase II

Fertilization among the F1 plants

9 : 3 : 3 : 1

14

14

14

14

YR yr yr yR

Gametes

Y

RRY

y

r

r

y

R Y y r

Ry

Y

r

Ry

Y

r

R

Y

r

y

r R

Y y

R

Y

r

y

R

Y

Y

R R

Y

r

y

r

y

R

y

r

Y

r

Y

r

Y

r

Y

R

y

R

y

R

y

r

Y

F2 Generation

Starting with two true-breeding pea plants,we follow two genes through the F1 and F2 generations. The two genes specify seed color (allele Y for yellow and allele y forgreen) and seed shape (allele R for round and allele r for wrinkled). These two genes are on different chromosomes. (Peas have seven chromosome pairs, but only two pairs are illustrated here.)

The R and r alleles segregate at anaphase I, yielding two types of daughter cells for this locus.

1

Each gamete gets one long chromosome with either the R or r allele.

2

Fertilizationrecombines the R and r alleles at random.

3

Alleles at both loci segregatein anaphase I, yielding four types of daughter cells depending on the chromosomearrangement at metaphase I. Compare the arrangement of the R and r alleles in the cellson the left and right

1

Each gamete gets a long and a short chromosome in one of four allele combinations.

2

Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation.

3

Morgan’s Experimental Evidence: Scientific Inquiry

Thomas Hunt MorganProvided convincing evidence that

chromosomes are the location of Mendel’s heritable factors

Morgan’s Choice of Experimental Organism Morgan worked with fruit flies

Because they breed at a high rate A new generation can be bred every two

weeksThey have only four pairs of chromosomes

Morgan first observed and notedWild type, or normal, phenotypes that were

common in the fly populations Traits alternative to the wild type

Are called mutant phenotypes

Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair

In one experiment Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) The F1 generation all had red eyes

The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes!

The F2 generation showed a typical Mendelian 3:1 ratio of red eyes to white eyes. However, no females displayed the white-eye trait; they all had red eyes. Half the males had white eyes,and half had red eyes.

Morgan then bred an F1 red-eyed female to an F1 red-eyed male toproduce the F2 generation.

RESULTS

PGeneration

F1

Generation

X

F2

Generation

Morgan mated a wild-type (red-eyed) female with a mutant white-eyed male. The F1 offspring all had red eyes.EXPERIMENT

Morgan determined That the white-eye mutant allele must be

located on the X chromosome

CONCLUSION Since all F1 offspring had red eyes, the mutant white-eye trait (w) must be recessive to the wild-type red-eye trait (w+). Since the recessive trait—white eyes—was expressed only in males in the F2 generation, Morgan hypothesized that the eye-color gene is located on the X chromosome and that there is no corresponding locus on the Y chromosome, as diagrammed here.

PGeneration

F1

Generation

F2

Generation

Ova(eggs)

Ova(eggs)

Sperm

Sperm

XX X

XY

WW+

W+

W

W+W+ W+

W+

W+

W+

W+

W+

W

W+

W W

W

Morgan’s discovery that transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color traitWas the first solid evidence indicating that a

specific gene is associated with a specific chromosome

Was the first evidence to show that certain traits/genes were inherited differently in males and females as these genes were sex-linked genes

Sex-linked genes

Sex-linked genes exhibit unique patterns of inheritance An organism’s sex

Is an inherited phenotypic character determined by the presence or absence of certain chromosomes

In humans and other mammalsThere are two varieties of sex chromosomes,

X and Y

(a) The X-Y system

44 +XY

44 +XX

Parents

22 +X

22 +Y

22 +XY

Sperm Ova

44 +XX

44 +XY

Zygotes(offspring)

Different systems of sex determinationAre found in other organisms

22 +XX

22 +X

76 +ZZ

76 +ZW

16(Haploid)

16(Diploid)

(b) The X–0 system

(c) The Z–W system

(d) The haplo-diploid system

Inheritance of Sex-Linked Genes The sex chromosomes

Have genes for many characters unrelated to sex A gene located on either sex chromosome

Is called a sex-linked gene In humans, the X chromosome is bigger than the

Y chromosome and hence contains more genes than the Y chromosome

X-linked genes are the genes on the X chromosome while Y-linked genes are the genes on the Y chromosome

Y-linked genes

The Y chromosome has few genes among which is the sex-determining gene which causes a foetus to develop as a male.

It also carries the gene for male fertility Traits influenced by the Y-linked genes are

passed from father to son and are never observed in females. One example is the inheritance of the gene for the male pattern of baldness

X-linked genes The X chromosome carries a greater number of

genes compared to the Y chromosome and as such for X-linked traits, there is usually no allele on the Y chromosome.

Males, therefore, have only one allele of the X-linked genes and are neither homozygous nor heterozygous for these genes but are said to be hemizygous

Most of the sex-linked traits seen in humans are actually X-linked traits

Sex-linked genesFollow specific patterns of inheritance

XAXA XaY

Xa Y

XAXa XAY

XAYXAYa

XA

XA

Ova

Sperm

XAXa XAY

Ova XA

Xa

XAXA XAY

XaYXaYA

XA YSperm

XAXa XaY

Ova

Xa Y

XAXa XAY

XaYXaYa

XA

Xa

A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation.

If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder.

If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.

(a)

(b)

(c)

Sperm

Some recessive alleles found on the X chromosome in humans cause certain types of disordersColor blindnessDuchenne muscular dystrophyHemophilia

Pattern of inheritance for X-linked traits

Indicators of X-linked traits:1. The traits appear to affect more males compared to

females. This is because females have 2 X chromosomes and if a particular trait is caused by a recessive allele, the female has a dominant allele to mask the effect of the recessive allele and therefore the incidence of the trait is rare in females and will only be seen in females homozygous recessive for the trait. Males, however, have only on allele on their only X chromosome and therefore will have a higher chance of exhibiting the X-linked trait

2. The trait will switch sexes from one generation to the next. The trait will appear to jump from the father to the daughter or from the mother to the son.

This is because, daughters always inherit their father’s only X chromosome and either one of her mother’s X chromosome and may be phenotypically normal but a carrier as well if heterozygous for a X-linked trait

Sons will always inherit one of their mother’s X chromosome and father’s Y chromosome and therefore will inherit the X-linked trait from their mothers

Linked genes tend to be inherited together because they are located near each other on the same chromosome

Each chromosomeHas hundreds or thousands of genes

Linked genes/Autosomal linkage

How Linkage Affects Inheritance: Scientific Inquiry Morgan did other experiments with fruit

fliesTo see how linkage affects the inheritance of

two different characters

Morgan crossed flies That differed in traits of two different characters Morgan determined that Genes that are close together on the same chromosome are linked and do not assort independently Unlinked genes are either on separate chromosomes or are far apart on the same chromosome and

assort independently

Recombination of Unlinked Genes: Independent Assortment of Chromosomes

When Mendel followed the inheritance of two charactersHe observed that some offspring have

combinations of traits that do not match either parent in the P generation

Gametes from green-wrinkled homozygousrecessive parent (yyrr)

Gametes from yellow-roundheterozygous parent (YyRr)

Parental-type offspring

Recombinantoffspring

YyRr yyrr Yyrr yyRr

YR yr Yr yR

yr

Recombinant offspringAre those that show new combinations of the

parental traits When 50% of all offspring are recombinants

Geneticists say that there is a 50% frequency of recombination

Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked

But due to the appearance of recombinant phenotypes, the linkage appeared incomplete Linkage can be determined by carrying out test crosses and observing the ratio obtained A test cross between a double heterozygote and a double recessive homozygote would

not yield the expected ratio of 1:1:1:1 proving that independent assortment has not occurred and that the genes are linked i.e. found on the same pair of chromosomes

Morgan proposed thatSome process must occasionally break the

physical connection between genes on the same chromosome

Crossing over of homologous chromosomes was the mechanism

Testcrossparents

Gray body,normal wings(F1 dihybrid)

b+ vg+

b vgReplication ofchromosomes

b+ vg

b+vg+

b

vg

vgMeiosis I: Crossingover between b and vgloci produces new allelecombinations.

Meiosis II: Segregationof chromatids producesrecombinant gameteswith the new allelecombinations.

Recombinantchromosome

b+vg+ b   vg b+ vg b vg+

b vg

Sperm

b   vg

b   vgReplication ofchromosomesvg

vg

b

b

bvg

b   vg

Meiosis I and II:Even if crossing overoccurs, no new allelecombinations areproduced.

OvaGametes

Testcrossoffspring

Sperm

b+  vg+ b   vg b+   vg b   vg+

965Wild type

(gray-normal)b+  vg+

b  vg b  vg b  vg b  vg

b  vg+b+  vg+b  vg+

944Black-

vestigial

206Gray-

vestigial

185Black-normal Recombination

frequency =391 recombinants

2,300 total offspring 100 = 17%

Parental-type offspring Recombinant offspring

Ova

b vg

Black body,vestigial wings(double mutant)

b

Linked genes Exhibit recombination frequencies less than 50%

Linkage Mapping: Using Recombination Data: Scientific Inquiry

A genetic map Is an ordered list of the genetic loci along a

particular chromosomeCan be developed using recombination

frequencies

A linkage map Is the actual map of a chromosome based on

recombination frequencies

Recombinationfrequencies

9% 9.5%

17%

b cn vgChromosome

The b–vg recombination frequency is slightly less than the sum of the b–cn and cn–vg frequencies because double crossovers are fairly likely to occur between b and vg in matings tracking these two genes. A second crossoverwould “cancel out” the first and thus reduce the observed b–vg recombination frequency.

In this example, the observed recombination frequencies between three Drosophila gene pairs (b–cn 9%, cn–vg 9.5%, and b–vg 17%) best fit a linear order in which cn is positioned about halfway between the other two genes:

RESULTS

A linkage map shows the relative locations of genes along a chromosome.APPLICATION

TECHNIQUE A linkage map is based on the assumption that the probability of a crossover between twogenetic loci is proportional to the distance separating the loci. The recombination frequencies used to constructa linkage map for a particular chromosome are obtained from experimental crosses, such as the cross depictedin Figure 15.6. The distances between genes are expressed as map units (centimorgans), with one map unitequivalent to a 1% recombination frequency. Genes are arranged on the chromosome in the order that best fits the data.

The farther apart genes are on a chromosomeThe more likely they are to be separated

during crossing over

Many fruit fly genes Were mapped initially using recombination

frequencies from test crosses

Mutant phenotypes

Short aristae

Black body

Cinnabareyes

Vestigialwings

Brown eyes

Long aristae(appendageson head)

Gray body

Redeyes

Normalwings

Redeyes

Wild-type phenotypes

IIY

I

X IVIII

0 48.5 57.5 67.0 104.5

X inactivation in Female Mammals In mammalian females

One of the two X chromosomes in each cell is randomly inactivated during embryonic development

If a female is heterozygous for a particular gene located on the X chromosome She will be a mosaic for that character

Two cell populationsin adult cat:

Active X

Orangefur

Inactive X

Early embryo:X chromosomes

Allele forblack fur

Cell divisionand X

chromosomeinactivation

Active X

Blackfur

Inactive X

Lethal genes

Combinations of alleles can lethal to an organism.

Eg. In cats, a dominant allele causes cats to have a stubby tail (Manx-tailed) but is lethal when both dominant alleles are together. Therefore, all Manx-tailed cats are heterozygous as the homozygous dominant form is lethal

Mutations

There are 2 types of mutations:

1. Gene / point mutation

2. Chromosomal mutation

Alterations of chromosome number or structure cause some genetic disorders

Causes include: Deletion, inversion, translocation or duplication of the chromosomes besides errors during meiosis

Large-scale chromosomal alterations Often lead to spontaneous abortions or cause a variety of developmental

disorders Types of mutations:

1. Abnormal chromosome number – aneuploidy

2. Abnormal number of sets of chromosomes – polyploidy

3. Alteration in chromosome structure

Chromosomal mutations

Abnormal Chromosome Number When nondisjunction occurs

Pairs of homologous chromosomes do not separate normally during meiosis

Gametes contain two copies or no copies of a particular chromosome

Meiosis I

Nondisjunction

Meiosis II

Nondisjunction

Gametes

n + 1n + 1 n 1 n – 1 n + 1 n –1 n nNumber of chromosomes

Nondisjunction of homologouschromosomes in meiosis I

Nondisjunction of sisterchromatids in meiosis II

(a) (b)

AneuploidyResults from the fertilization of gametes in

which nondisjunction occurred Is a condition in which offspring have an

abnormal number of a particular chromosome

If a zygote is trisomic It has three copies of a particular

chromosomeExample: Down’s Syndrome

If a zygote is monosomic It has only one copy of a particular

chromosome

Down Syndrome Is usually the result of an extra chromosome

21, trisomy 21

Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes

Produces a variety of aneuploid conditions

Klinefelter syndrome Is the result of an extra chromosome in a male,

producing XXY individuals Turner syndrome

Is the result of monosomy X, producing an X0 karyotype

Polyploidy Is a condition in which there are more than two complete sets of chromosomes in an organism Could be due to failure of pairs of homologous chromosomes or sister chromatids to separate

during meiosis resulting in the formation of a diploid gamete. When a diploid gamete is fertilized with a haploid gamete, the result is a triploid (3n) organism. If a diploid gamete is fertilized with another diploid gamete, the result is a tetraploid (4n)

organism Polyploidy is common in plants but for animals a polyploid organism is usually inviable

Alterations of Chromosome Structure

Breakage of a chromosome can lead to four types of changes in chromosome structureDeletionDuplication InversionTranslocation

Alterations of chromosome structure

A B C D E F G HDeletion

A B C E G HF

A B C D E F G HDuplication

A B C B D EC F G H

A

A

M N O P Q R

B C D E F G H

B C D E F G HInversion

Reciprocaltranslocation

A B P Q R

M N O C D E F G H

A D C B E F HG

(a) A deletion removes a chromosomal segment.

(b) A duplication repeats a segment.

(c) An inversion reverses a segment within a chromosome.

(d) A translocation moves a segment fromone chromosome to another,nonhomologous one. In a reciprocal

  translocation, the most common type,nonhomologous chromosomes exchangefragments. Nonreciprocal translocationsalso occur, in which a chromosome transfers a fragment without receiving afragment in return.

Human Disorders Due to Chromosomal Alterations

Alterations of chromosome number and structureAre associated with a number of serious

human disorders

Certain cancersAre caused by translocations of chromosomes

Normal chromosome 9Reciprocal

translocation

Translocated chromosome 9

Philadelphiachromosome

Normal chromosome 22 Translocated chromosome 22