mendelian inheritance - college biology

1

The Chromosomal

Basis of

Inheritance

Beyond Mendelian Ideas• Mendel’s “hereditary factors” were genes,

though this wasn’t known at the time

• Now we know that genes are located on

chromosomes at specific loci

• The location of a particular gene can be seen

by tagging isolated chromosomes with a

fluorescent dye that highlights the gene

Mendelian inheritance

• The chromosome theory of inheritance states:

– Mendelian genes have specific loci (positions) on chromosomes

– Chromosomes undergo segregation and independent assortment

• The behavior of chromosomes during meiosis is said to account for Mendel’s laws of segregation and independent assortment

P Generation Yellow-round

seeds (YYRR)

Y

F1 Generation

Y

R R

R Y

r

r

r

y

y

y

Meiosis

Fertilization

Gametes

Green-wrinkled

seeds (yyrr)

All F1 plants produce

yellow-round seeds (YyRr)

R R

YY

r ry y

Meiosis

R R

Y Y

r r

y y

Metaphase I

Y Y

R Rrr

y y

Anaphase I

r r

y Y

Metaphase IIR

Y

R

y

yyy

RR

YY

rrrr

yYY

R R

yRYryrYR1/4

1/41/4 1/4

F2 Generation

Gametes

An F1 F1 cross-fertilization

9 : 3 : 3 : 1

LAW OF INDEPENDENT

ASSORTMENT Alleles of genes

on nonhomologous

chromosomes assort

independently during gamete

formation.

LAW OF SEGREGATION

The two alleles for each gene

separate during gamete

formation.

1

2

33

2

1

Morgan’s Experiments• The first solid evidence associating a specific gene with a

specific chromosome came from Thomas Hunt Morgan, an

embryologist

• Morgan’s experiments with fruit flies provided convincing

evidence that chromosomes are the location of Mendel’s

heritable factors

• Several characteristics make fruit flies a convenient

organism for genetic studies:

– They breed at a high rate

– A generation can be bred every two weeks

– They have only four pairs of chromosomes

• Morgan noted wild type, or normal, phenotypes that were

common in the fly populations

• Traits alternative to the wild type are called mutant

phenotypes

2

Behavior: Alleles vs. Chromosome Pairs

• 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

• Morgan determined that the white-eyed mutant allele must be located on the X chromosome

• Morgan’s finding supported the chromosome theory of inheritance

PGeneration

Generation

Generation

Generation

Generation

Generation

F1

F2

All offspring

had red eyes

Sperm

EggsF1

F2

P

Sperm

Eggs

XX

XY

CONCLUSION

EXPERIMENT

RESULTS

w

w

w

w

w

w

w w

+

+

++ +

w

ww w

w

w

w

ww

+

+

+

+ +

+

Morgan mated

white eyed male

(mutant) with red

eyed female

(wild type)

Result all F1 had red eyes

An F2 cross produced a 3:1 red:white eye ratio, but only males had white eyes

Morgan determined the white-eyed mutant allele is located on the X chromosome

Morgan’s finding supported the chromosome theory of inheritance

Sex-linked genes

• In humans and some other animals, there is a

chromosomal basis of sex determination

• Humans – XY

• The SRY gene on the Y chromosome codes for the

development of testes

• Females – XX

• males are XY

• Each ovum contains an X

• Sperm contains either an X or a Y (a) The X-Y system

44 +XY

44 +XX

Parents

44 +XY

44 +XX

22 +X

22 +X

22 +Yor

or

Sperm Egg

+

Zygotes (offspring)

Sex Chromosomes - Humans

(b) The X-0 system

22 +XX

22 +X

Sex Chromosomes - Grasshoppers

(c) The Z-W system

76 +ZW

76 +ZZ

Sex Chromosomes - Birds

3

(d) The haplo-diploid system

32(Diploid)

16(Haploid)

Sex Chromosomes – Bees Inheritance of Sex-Linked Genes

• A gene located on either sex chromosome is a sex-linked

gene

• Sex-linked genes follow specific patterns of inheritance, for

a recessive sex-linked trait to be expressed

– A female needs two copies of the allele

– A male needs only one copy of the allele (he only gets

one X chromosome)

• Sex-linked recessive disorders are much more common in

males than in females because they are found on the X

chromosome

(a) (b) (c)

XNXN XnY XNXn XNY XNXn XnY

YXnSpermYXNSpermYXnSperm

XNXnEggs XN

XN XNXn

XNY

XNY

Eggs XN

Xn

XNXN

XnXN

XNY

XnY

Eggs XN

Xn

XNXn

XnXn

XNY

XnY

Transmission of an X-linked recessive

disorder

X linked disorders: Color blindness, Duchenne muscular

dystrophy and Hemophilia

X Inactivation in Female Mammals

• In mammalian females, one of the two X chromosomes

in each cell is randomly inactivated during embryonic

development

• The inactive X condenses into a Barr body

• If a female is heterozygous for a particular gene located

on the X chromosome, she will be a mosaic for that

character

X chromosomes

Early embryo:

Allele for

orange fur

Allele for

black fur

Cell division and

X chromosomeinactivationTwo cell

populationsin adult cat:

Active X

Active XInactive X

Black fur Orange fur

• Linked genes tend to be inherited together because

they are located near each other on the same

chromosome

• Genes located on the same chromosome that tend to

be inherited together are called linked genes

• Morgan did other experiments with fruit flies to see how

linkage affects inheritance of two characters

• Morgan crossed flies that differed in traits of body color

and wing size

Linked Genes

4

b+ vg+

Parents in testcross

Most offspring

b+ vg+

b vg

b vg

b vg

b vg

b vg

b vg

or

EXPERIMENTP Generation (homozygous)

Wild type

(gray body,normal wings)

Double mutant

(black body,vestigial wings)

b b vg vgb+ b+ vg+ vg+


Wild type


Double mutant


b b vg vg

b b vg vg

Double mutantTESTCROSS

b+ b+ vg+ vg+

F1 dihybrid

(wild type)

b+ b vg+ vg


Wild type


Double mutant


b b vg vg

b b vg vg


b+ b+ vg+ vg+

F1 dihybrid

(wild type)

b+ b vg+ vg

Testcrossoffspring

Eggs b+ vg+ b vg b+ vg b vg+

Black-

normalGray-

vestigialBlack-

vestigialWild type

(gray-normal)

b vg

Sperm

b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg


RESULTS

Wild type


Double mutant


b b vg vg

b b vg vg


b+ b+ vg+ vg+

F1 dihybrid

(wild type)

b+ b vg+ vg

Testcrossoffspring

Eggs b+ vg+ b vg b+ vg b vg+

Black-

normalGray-

vestigialBlack-

vestigialWild type

(gray-normal)

b vg

Sperm

b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg

PREDICTED RATIOS

If genes are located on different chromosomes:

If genes are located on the same chromosome and

parental alleles are always inherited together:

1

1

1

1

1 1

0 0

965 944 206 185

:

:

:

:

:

:

:

:

:

• Morgan found that body color and wing size are usually

inherited together in specific combinations (parental

phenotypes)

• He noted that these genes do not assort independently,

and reasoned that they were on the same chromosome

• However, non-parental phenotypes (recombinant types)

were also produced

• Understanding this result involves exploring genetic

recombination - the production of offspring with

combinations of traits differing from either parent. (We did

this in Meiosis!)

• The genetic findings of Mendel and Morgan relate to the

chromosomal basis of recombination

Genetic Recombination and Linkage

5

YyRr

Gametes from green-

wrinkled homozygousrecessive parent (yyrr)

Gametes from yellow-round

heterozygous parent (YyRr)

Parental-

typeoffspring

Recombinant

offspring

yr

yyrr Yyrr yyRr

YR yr Yr yR

Recombination of Unlinked Genes:

Independent Assortment of Chromosomes

Combinations of traits in some offspring

differ from either parent

Phenotype matching one of the parental

phenotypes are parental types

Non-parental phenotypes (new

combinations of traits) are recombinant

types, or recombinants

A 50% frequency of recombination is

observed for any two genes on different

chromosomes

Recombination of Linked Genes: Crossing Over

• Morgan discovered that genes can be linked, but the

linkage was incomplete, as evident from recombinant

phenotypes

• Morgan proposed that some process must sometimes

break the physical connection between genes on the same

chromosome

• That mechanism was the crossing over of homologous

chromosomes

Testcross

parents

Replication

of chromo-somes

Gray body, normal wings

(F1 dihybrid)

Black body, vestigial wings

(double mutant)

Replication

of chromo-somes

b+ vg+

b+ vg+

b+ vg+

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b+ vg+

b+ vg

b vg+

b vg

Recombinantchromosomes

Meiosis I and II

Meiosis I

Meiosis II

b vg+b+ vgb vgb+ vg+

Eggs

Testcrossoffspring

965Wild type

(gray-normal)

944Black-

vestigial

206Gray-

vestigial

185Black-normal

b+ vg+

b vg b vg

b vg b+ vg

b vg b vg

b vg+

Sperm

b vg

Parental-type offspring Recombinant offspring

Recombinationfrequency

=391 recombinants

2,300 total offspring 100 = 17%

Big Idea Here!

The further

apart genes

are on a

chromosome

the less likely

that that will

be transferred

together in a

cross over

event. Genes

located very

close to one

another close

to the end of

the same

choromosome

or chromotid

are often

transferred

together by

default of their

position.

Testcross

parents

Replication

of chromo-somes

Gray body, normal wings(F1 dihybrid)

Black body, vestigial wings(double mutant)

Replication

of chromo-somes

b+ vg+

b+ vg+

b+ vg+

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b+ vg+

b+ vg

b vg+

b vg


Meiosis I and II

Meiosis I

Meiosis II

Eggs Sperm

b+ vg+ b vg b+ vg b vgb vg+

Parental types

Testcrossoffspring

965Wild type

(gray-normal)

944Black-

vestigial

206Gray-

vestigial

185Black-normal

b+ vg+

b vg b vg

b vg b+ vg

b vg

b vg

b+ vg+

Spermb vg

Parental-type offspring Recombinant offspring

Recombinationfrequency

=391 recombinants

2,300 total offspring 100 = 17%

b vg

b+ vg b vg+

b vg+

Eggs


Mapping the Distance Between Genes Using Recombination Data

• A genetic map, an ordered list of the genetic loci along a

particular chromosome

• The farther apart two genes are, the higher the probability

that a crossover will occur between them and therefore the

higher the recombination frequency

• A linkage map is a genetic map of a chromosome based

on recombination frequencies

• Distances between genes can be expressed as map

units; one map unit equals a 1% recombination frequency

• Map units indicate relative distance and order, not precise

locations of genes!

6

Recombinationfrequencies

Chromosome

9% 9.5%

17%

b cn vg

Genes that are far apart on the same chromosome can have a recombination

frequency near 50%

Such genes are physically linked, but genetically unlinked, and behave as if found

on different chromosomes• Recombination frequencies were used to make linkage

maps of fruit fly genes on a chromosome.

• Using methods like chromosomal banding, geneticists can

develop cytogenetic maps of chromosomes

• Cytogenetic maps indicate the positions of genes with

respect to chromosomal features

– Genes will have the same order but may have different

distances than a linkage map

Mutant phenotypesShortaristae

Blackbody

Cinnabareyes

Vestigialwings

Browneyes

Redeyes

Normalwings

Redeyes

Graybody

Long aristae(appendageson head)

Wild-type phenotypes

0 48.5 57.5 67.0 104.5

Alterations of chromosome number or structure cause some genetic disorders

• Gross changes to chromosome often lead to spontaneous

abortions (miscarriages) or cause a variety of

developmental disorders

• Major damage to a chromosome

• Extra or missing chromosomes

– Monosomy (2n-1)

– Trisomy (2n+1)

• Remember the Karyotype – looking for missing, extra or

damaged chromosomes?

Alterations of Chromosome Number

• Non-disjunction, pairs of homologous chromosomes fail

to separate normally during meiosis I or II.

• As a result, one gamete receives two of the same type of

chromosome, and another gamete receives no copy.

• Aneuploidy (having an abnormal chromosome #)

results from the fertilization of gametes in which non-

disjunction occurred

• A monosomic zygote has only one copy of a particular

chromosome

• A trisomic zygote has three copies of a particular

chromosome

Meiosis I

(a) Nondisjunction of homologouschromosomes in meiosis I

(b) Nondisjunction of sisterchromatids in meiosis II

Nondisjunction

7

Meiosis I

Nondisjunction



Meiosis II

Nondisjunction

Meiosis I

Nondisjunction



Meiosis II

Nondisjunction

Gametes

Number of chromosomes

n + 1 n + 1 n + 1n – 1 n – 1 n – 1 n n

Polyploidy

Polyploidy is a condition in which an organism has more

than two complete sets of chromosomes

– Triploidy (3n) is three sets of chromosomes

– Tetraploidy (4n) is four sets of chromosomes

Polyploidy is common in plants, but not animals

Polyploids are more normal in appearance than

aneuploids I’m a tetraploid!

Alterations of Chromosome Structure

• Breakage of a chromosome can lead to four types of

changes in chromosome structure:

– Deletion removes a chromosomal segment

– Duplication repeats a segment

– Inversion reverses a segment within a chromosome

– Translocation moves a segment from one

chromosome to another

DeletionA B C D E F G H A B C E F G H

(a)

(b)

(c)

(d)

Duplication

Inversion

Reciprocaltranslocation

A B C D E F G H

A B C D E F G H

A B C D E F G H

A B C B C D E F G H

A D C B E F G H

M N O C D E F G H

M N O P Q R A B P Q R

Human Disorders Due to Chromosomal Alterations

• Down Syndrome (Trisomy 21)

– ~ 1:700 births in the U.S

– frequency of Down syndrome

increases with the age of the

mother.

8

Aneuploidy of Sex Chromosomes

Nondisjunction of sex chromosomes produces a

variety of aneuploid conditions

• Monosomy X (Turner syndrome)

– Monosomy of Sex

Chromosomes; XO female

– Characteristics: Infertile/sterile,

dwarfism, overweight, some

mental retardation, webbed neck,

sterile

– it is the only known viable

monosomy in humans

• XXY (Klinefelter syndrome)

– Feminine characteristics, infertile, unusually tall,

– the result of an extra X chromosome in a male.

Disorders Caused by Structurally Altered Chromosomes

• The syndrome cri du chat (“cry of the cat”), results from a

specific deletion in chromosome 5

– A child born with this syndrome is mentally retarded

and has a catlike cry; individuals usually die in infancy

or early childhood

• Certain cancers, including chronic myelogenous leukemia

(CML), are caused by translocations of chromosomes

Normal chromosome 9

Normal chromosome 22

Translocated chromosome 9

Translocated chromosome 22(Philadelphia chromosome)

Reciprocaltranslocation

Exceptions to the standard chromosome theory

• There are two normal exceptions to Mendelian genetics

• One exception involves genes located in the nucleus, and

the other exception involves genes located outside the

nucleus

Genomic Imprinting• The phenotype depends on which parent donated the

alleles for that trait.

• This type of variation is called genomic imprinting

• Silencing occurs when certain genes that are methylated

during gamete production (addition of –CH3) of DNA,

remember this from functional groups. Methylation

silences the expression of that gene.

• Genomic imprinting is thought to affect only a small fraction

of mammalian genes

• Most imprinted genes are critical for embryonic

development

Normal Igf2 allele

is expressedPaternalchromosome

Maternalchromosome

(a) Homozygote

Wild-type mouse(normal size)

Normal Igf2 allele

is not expressed

Mutant Igf2 alleleinherited from mother

Mutant Igf2 alleleinherited from father

Normal size mouse(wild type)

Dwarf mouse(mutant)

Normal Igf2 alleleis expressed

Mutant Igf2 alleleis expressed

Mutant Igf2 alleleis not expressed

Normal Igf2 alleleis not expressed

(b) Heterozygotes

9

Inheritance of Organelle Genes

• Extra-nuclear genes (or cytoplasmic genes) are genes found in organelles in the cytoplasm (mitochondria and chloroplasts!)

• Extra-nuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg

• The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

• Some defects in mitochondrial genes prevent cells from

making enough ATP and result in diseases that affect the

muscular and nervous systems

– For example, mitochondrial myopathy and Leber’s

hereditary optic neuropathy

REVIEW

EggSperm

P generationgametes

CBAD E

F

D

F E

AB

C

e

d

f

c ba

d

f

e

cba

This F1 cell has 2n = 6chromosomes and isheterozygous for all sixgenes shown (AaBbCcDdEeFf).

Red = maternal; blue = paternal.

+

Each chromosomehas hundreds or

thousands of genes.

Four (A, B, C, F) areshown on this one.

The alleles of unlinkedgenes are either on

separate chromosomes

(such as d and e) or sofar apart on the samechromosome (c and f)that they assortindependently.

Genes on the same chromo-

some whose alleles are so

close together that they donot assort independently(such as a, b, and c) are saidto be linked.

mendelian inheritance - college biology

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