Chapter 15

Chromosomal basis for inheritance

Mendel Genetics Mendel published his work in 1866 1900 his work was rediscovered. Parallels between Mendel’s factors

& chromosome behavior

Mendel’s Genetics 1902 Walter Sutton Chromosomal theory of

inheritance Genes are located on chromosomes Located at specific loci (positions) Behavior of chromosomes during

meiosis account for inheritance patterns

Fig. 15-2P Generation Yellow-round

seeds (YYRR)

Y

F1 Generation

Y

R R

R Y

r

r

r

y

y

y

Meiosis

Fertilization

Gametes

Green-wrinkledseeds ( yyrr)

All F1 plants produceyellow-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

yRYryrYR1/41/4

1/41/4

F2 Generation

Gametes

An F1 F1 cross-fertilization

9 : 3 : 3 : 1

LAW OF INDEPENDENTASSORTMENT Alleles of geneson nonhomologouschromosomes assortindependently during gameteformation.

LAW OF SEGREGATIONThe two alleles for each geneseparate during gameteformation.

1

2

33

2

1

Thomas Morgan studied fruit flies Drosophila melanogaster Proved chromosomal theory correct Studied eye color Red is dominant, white is recessive Crossed a homozygous dominant

female with a homozygous recessive male

Fruit fly

Wild type (w+)

Mutant (w)

Fruit fly F1 offspring were all red eyed F2 classic 3:1 ratio red:white

phenotypes Showed the alleles segregate Supported the Chromosomal theory BUT only males were white eyed All females were red eyed or wild

type

Fig. 15-4

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

ww

w w

+

+

++ +

w

ww w

w

w

w

ww

+

+

+

+ +

+

Fruit fly Eye color gene is on the X-

chromosomes Sex-linked genes: Genes found on the sex

chromosomes X-chromosome has more genes than

Y-chromosome Most sex-linked genes are on the X-

chromosome

Human Males Y chromosome is very condensed 78 genes Male characteristics Sperm production & fertility

Males SRY is a gene on the Y chromosome Sex determining region of Y Present gonads develop into testes Determines development of male

secondary sex characteristics Not present then individual

develops ovaries

Females X chromosome has 1000 genes One of the 2 X chromosomes is

inactivated Soon after embryonic development Choice is random from cell to cell Female is heterozygous for a trait Some cells will have one allele Some cell have the other

Females Barr body: Condensed inactive X chromosome Stains dark

Fig. 15-8X chromosomes

Early embryo:

Allele fororange fur

Allele forblack fur

Cell division andX chromosomeinactivationTwo cell

populationsin adult cat:

Active XActive X

Inactive X

Black fur Orange fur

Sex-linked Mom passes gene on the X-

chromosome to the son Males have one X-chromosome Recessive gene is expressed Recessive alleles on the X are

present No counter alleles on the Y

Sex-linked disorders Mom passes sex-linked to sons &

daughters Dad passes only to daughters

Sex-linked disorders Sex-linked genetic defects Hemophilia 1/10,000 Caucasian males

Sex-linked disorders Colored blindness Red-green blindness Mostly males Heterozygous females can have

some defects

Sex-linked disorders Duchenne muscular dystrophy Almost all cases are male Child born healthy Muscles become weakened Break down of the myelin sheath in

nerve stimulating muscles Wheelchair by 12 years old Death by 20

Independent assortment

Independent assortment Dihybrid testcross 50% phenotypes similar to parents Parental types 50% phenotypes not similar to parents Recombinant types Indicates unlinked genes Mendel’s independent assortment

Test cross

Linked genes Do not assort independently Genes are inherited together Genes located on same

chromosome Differs from Mendel’s law of

independent assortment

Linked genes Test cross fruit flies Wild-type (dihybrid) Gray bodies and long wings Mutants (homozygous) Black bodies and short wings

(vestigial) Results not consistent with genes

being on separate chromosomes

Fig. 15-10Testcrossparents

Replicationof chromo-somes

Gray body, normal wings(F1 dihybrid)

Black body, vestigial wings(double mutant)

Replicationof chromo-somes

b+ vg+

b+ vg+

b+ vg+

b vg

b vg

b vg

b vg

b vg

b vg

b vgb 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 recombinants2,300 total offspring

100 = 17%

Linked genes More parental phenotypes Than if on separate chromosomes Greater than 50% Gray body normal wings or black body

vestigial Non-parental phenotype 17% Gray-vestigial or black-normal wings Indicating crossing over

Genetic recombination: New combination of genes 2 genes that are farther apart tend

to cross over more 2 genes on the same chromosome

can show independent assortment Due to regularly crossing over

Genetic map Ordered list of gene loci Linkage map: Genetic map based on recombination

frequencies Distance between genes in terms of

frequency of crossing over Higher percentage of crossing over the

further apart the genes are Centimorgan (Thomas Hunt Morgan) A map unit

Fig. 15-12

Mutant phenotypes

Shortaristae

Blackbody

Cinnabareyes

Vestigialwings

Browneyes

Redeyes

Normalwings

Redeyes

Graybody

Long aristae(appendageson head)

Wild-type phenotypes

0 48.5 57.5 67.0 104.5

Human genetic map Genetic distance is still

proportional to the recombination frequency

Use pedigrees Newer technology

Alterations in chromosomes Chromosome number Chromosome structure Serious human disorders

Alterations in numbers Nondisjunction Failure of homologues or sister

chromatids to separate properly Aneuploidy: Gain or a loss of chromosomes due to

nondisjunction Abnormal number of chromosomes Occurs about 5% of the time with

humans

Nondisjunction

Fig. 15-13-3

Meiosis I

Nondisjunction

(a) Nondisjunction of homologous chromosomes in meiosis I

(b) Nondisjunction of sister chromatids in meiosis II

Meiosis II

Nondisjunction

Gametes

Number of chromosomes

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

Monosomics Lost a copy of a chromosome (not

a sex chromosome) Usually do not survive Trisomes: gained a copy of a

chromosome Many do not survive either 35% rate of aneuploidy

(spontaneous abortions)

Polyploidy More than 2 sets of chromosomes 3n or 4n Plants

Fig. 15-14

Alterations in Structure 1. Deletion: Missing a section of chromosome 2. Duplication: Extra section of chromosome Attaches to sister or non-sister

chromatids

Alterations in Structure 3. Inversion: Reverse orientation of section of

chromosome 4. Translocation: Chromosome fragment joins a

nonhomologous chromosome

Fig. 15-15

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 Trisomes Babies with extra chromosomes

can survive Chromosome 13, 15, 18, 21 and 22 These are the smallest

chromosomes

Trisomy 13

Trisomy 18

Down syndrome Trisomy 21 1866 J. Langdon Down 1 in 750 births Similar distribution in all racial

groups Similar distribution in chimps and

other primates

Down Syndrome Mental retardation Heart disease Intestinal problems/surgery Hearing problems/hearing loss Unstable joints Leukemia Single crease in the palm

Down syndrome 20 years or younger 1 in 1700 20-30 years 1 in 1400 30-35 years 1 in 750 45 1 in 16

Nondisjunction Higher incidence in woman’s eggs

than in the men’s sperm Woman’s eggs are in prophase I

(meiosis) when she is born Her eggs are as old as she is!!! Men produce new sperm daily

Down Syndrome Primarily from nondisjunction Chromosome in woman’s eggs. Therefore age of mom is very

important

Sex chromosomes X chromosomes fail to separate

properly Some eggs with 2 X chromosomes Some eggs with no X chromosome Produce XXX Appears normal

Sex chromosomes XXY Klinefelter syndrome (1 in 500

male births) Is a male with some female features Sterile Maybe slightly slower than normal OY does not survive, need the X

chromosome

Sex chromosomes XO, Turner syndrome Female that has short statue, web

neck Sterile 1 in 5000 births

Sex Chromosomes XYY 1 in 1000 births Normal fertile males May be taller than normal

Translocation Philadelphia chromosome Reciprocal exchange of

chromosome #22 and #9 exchange portions Shortened translocated #22 CML

Fig. 15-17

Normal chromosome 9

Normal chromosome 22

Reciprocaltranslocation Translocated chromosome 9

Translocated chromosome 22(Philadelphia chromosome)

Deletion Cri du chat “Cry of the cat” Deletion of chromosome 5 Mental retardation Small head Die in infancy

Genomic imprinting Variation in phenotype Depends on allele is inherited from

male or female Usually autosomes Silencing of one allele in gamete

formation

Fig. 15-18Normal Igf2 alleleis expressed

Paternalchromosome

Maternalchromosome

Normal Igf2 alleleis not expressed

Mutant Igf2 alleleinherited from mother

(a) Homozygote

Wild-type mouse(normal size)

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

Organelle genes Extracellular genes Cytoplasmic genes