Genetics

The study of inherited traits:An introduction

Molecular GeneticsChromosome

DNA

Nucleotides

Nucleus

Cell

History of Genetics

• Mid 19th century (1850)– Darwin & Wallace • Theories of evolution

– Lamarck• Theories on acquisition of heritable traits

– Mendel• Theories on transmission of traits

History of Genetics• Pioneering work of Mendel was done in ignorance of cell division –

particularly meiosis, and the nature of genetic material – DNA

• 1869 - Friedrich Miescher identified DNA

• 1900-1913 – Chromosomal theory of inheritance – Sutton & Boveri– Genes on chromosomes – TH Morgan– Genes linearly arranged on chromosomes & mapped – AH Sturtevant

• 1941 – George Beadle & Ed Tatum related "gene" to enzyme & biochemical processes

• 1944 – Oswald Avery demonstrated that DNA was genetic material

Early Ideas

• Until the 20th century, many biologists erroneously believed that – characteristics acquired during lifetime could be

passed on – characteristics of both parents blended

irreversibly in their offspring

• Modern genetics began with Gregor Mendel’s quantitative experiments with pea plants

Mendel

Figure 9.2A, B

Stamen

Carpel

• Mendel crossed pea plants that differed in certain characteristics and traced the traits from generation to generation

Figure 9.2C

• This illustration shows his technique for cross-fertilization

1 Removed stamensfrom purple flower

White

Stamens

Carpel

PurplePARENTS(P)

OFF-SPRING

(F1)

2 Transferred pollen from stamens of white flower to carpel of purple flower

3 Pollinated carpel matured into pod

4 Planted seeds from pod

• Mendel studied seven pea characteristics - phenotypes

Figure 9.2D

• He hypothesized that there are alternative forms of genes (although he did not use that term), the units that determine heredity

FLOWER COLOR

FLOWER POSITION

SEED COLOR

SEED SHAPE

POD SHAPE

POD COLOR

STEM LENGTH

Purple White

Axial Terminal

Yellow Green

Round Wrinkled

Inflated Constricted

Green Yellow

Tall Dwarf

• From his experimental data, Mendel deduced that an organism has two genes (alleles) for each inherited characteristic– One characteristic

(phenotype) comes from each parent

Principle of SegregationP GENERATION(true-breedingparents)

F1 generation

F2generation

Purple flowers White flowers

All plants have purple flowers

Fertilization among F1 plants(F1 x F1)

3/4 of plantshave purple flowers

1/4 of plantshave white flowersFigure 9.3A

• A sperm or egg carries only one allele of each pair

– The pairs of alleles separate when gametes form

– This process describes Mendel’s law of segregation

– Alleles can be dominant or recessive

GENETIC MAKEUP (ALLELES)

PLANTS

F1 PLANTS(hybrids)

F2 PLANTS

PP pp

All P All p

All Pp

1/2 P 1/2 p

EggsP

p

P

PPp

Sperm

Pp Pp

pp

Gametes

Gametes

Phenotypic ratio3 purple : 1 white

Genotypic ratio1 PP : 2 Pp : 1 pp

Figure 9.3B

• Alternative forms of a gene (alleles) reside at the same locus on homologous chromosomes

Homologous chromosomes bear the two alleles for each characteristic

GENE LOCI

Figure 9.4

P a B

DOMINANTallele

RECESSIVEallele

P a b

GENOTYPE: PP aa Bb

HOMOZYGOUSfor thedominant allele

HOMOZYGOUSfor therecessive allele

HETEROZYGOUS

• By looking at two characteristics at once, Mendel found that the alleles of a pair segregate independently of other allele pairs during gamete formation– This is known as the principle of independent

assortment

The principle of independent assortment

Figure 9.5A

HYPOTHESIS: DEPENDENT ASSORTMENT

HYPOTHESIS: INDEPENDENT ASSORTMENT

PGENERATION

F1

GENERATION

F2

GENERATION

RRYY rryy

Gametes RY

Yellowround

ry

RrYy

Eggs SpermRY

ry

RY

ry

1/21/2

1/21/2

Actual resultscontradict hypothesis

RRYY rryy

RY ryGametes

RrYy

Eggs RY

rY

1/4

1/4

Ry

ry

1/4

1/4

RY

rY

Ry

ry

1/4

1/4

1/4

1/4

RRYY

RrYYRrYY

RRYy rrYY RrYy

RrYyRrYyRrYyRrYy

rrYy RRyy rrYy

Rryy Rryy

rryy

9/16

3/16

3/16

1/16

Greenround

YellowwrinkledYellowwrinkled

ACTUAL RESULTSSUPPORT

HYPOTHESIS

• Independent assortment of two genes in the Labrador retriever

Figure 9.5B

PHENOTYPES Black coat, normal vision

B_N_

Blind

GENOTYPES

MATING OF HETEROZYOTES(black, normal vision)

PHENOTYPIC RATIO OF OFFSPRING

Black coat, blind (PRA)

B_nn

Chocolate coat, normal vision

bbN_

Chocolate coat, blind (PRA)

bbnn

9 black coat,normal vision

3 black coat,blind (PRA)

3 chocolate coat,normal vision

1 chocolate coat,blind (PRA)

Blind

BbNnBbNn

• The offspring of a testcross often reveal the genotype of an individual when it is unknown

Geneticists use testcross to determine unknown genotypes

TESTCROSS:

B_GENOTYPES bb

BB Bbor

Two possibilities for the black dog:

GAMETES

OFFSPRINGaAll black 1 black : 1 chocolate

B

b

B

b

b

Bb Bb bb

Figure 9.6

• Inheritance follows the rules of probability– The rule of

multiplication and the rule of addition can be used to determine the probability of certain events occurring

Mendel’s principles reflect the rules of probability

F1 GENOTYPES

Bb female

F2 GENOTYPES

Formation of eggs

Bb male

Formation of sperm

1/2

1/2

1/2

1/21/4

1/41/4

1/4

B B

B B

B B

b

b b

b

b b

Figure 9.7

• The inheritance of many human traits follows Mendel’s principles and the rules of probability

Family pedigrees

Figure 9.8A

• Family pedigrees are used to determine patterns of inheritance and individual genotypes

Figure 9.8B

DdJoshuaLambert

DdAbigailLinnell

D_Abigail

Lambert

Female

DdElizabeth

Eddy

D_JohnEddy

? D_HepzibahDaggett

?

?

ddDdDdDdddDdDd

MaleDeaf

Hearing

ddJonathanLambert

• Most such disorders are caused by autosomal recessive alleles– Examples:

cystic fibrosis, sickle-cell disease

Many inherited disorders are controlled by a single gene

Figure 9.9A

D D

d d

NormalDd

NormalDd

DDNormal

DdNormal(carrier)

DdNormal(carrier)

ddDeaf

Eggs Sperm

PARENTS

OFFSPRING

• A few are caused by dominant alleles

Figure 9.9B

– Examples: achondroplasia, Huntington’s disease

Table 9.9

• Karyotyping and biochemical tests of fetal cells and molecules can help people make reproductive decisions– Fetal cells can be obtained through amniocentesis

Fetal testing for inherited disorders

Figure 9.10A

Amnioticfluid

Fetus(14-20weeks)

Placenta

Amnioticfluidwithdrawn

Centrifugation

Fetalcells

Fluid

Uterus Cervix Cell culture

Severalweeks later Karyotyping

Biochemicaltests

• Chorionic villus sampling is another procedure that obtains fetal cells for karyotyping

Figure 9.10B

Fetus(10-12weeks)Placenta

Chorionic villi

Suction

Several hourslater

Fetal cells(from chorionic villi)

Karyotyping

Some biochemical

tests

• Examination of the fetus with ultrasound is another helpful technique

Figure 9.10C, D

• Mendel’s principles are valid for all sexually reproducing species– However, often the genotype does not dictate the

phenotype in the simple way his principles describe

VARIATIONS ON MENDEL’S PRINCIPLESThe relationship of genotype to phenotype is rarely

simple

• When an offspring’s phenotype—such as flower color— is in between the phenotypes of its parents, it exhibits incomplete dominance

Incomplete dominance results in intermediate phenotypes

P GENERATION

F1 GENERATION

F2 GENERATION

RedRR

Gametes R r

Whiterr

PinkRr

R r

R R

r r

1/21/2

1/2

1/21/2

1/2 SpermEggs

PinkRr

PinkrR

Whiterr

RedRR

Figure 9.12A

• Incomplete dominance in human hypercholesterolemia

Figure 9.12B

GENOTYPES:HH

Homozygousfor ability to make

LDL receptors

HhHeterozygous

hhHomozygous

for inability to makeLDL receptors

PHENOTYPES:

LDL

LDLreceptor

Cell

Normal Mild disease Severe disease

• In a population, multiple alleles often exist for a characteristic– The three alleles for ABO blood type in humans is an

example

9.13 Many genes have more than two alleles in the population

Figure 9.13

– The alleles for A and B blood types are codominant, and both are expressed in the phenotype

BloodGroup(Phenotype)

O

Genotypes

AntibodiesPresent inBlood

Reaction When Blood from Groups Below Is Mixed with Antibodies from Groups at Left

O A B AB

A

B

AB

ii

IA IA

orIA i

IB IB

orIB i

IA IB

Anti-AAnti-B

Anti-B

Anti-A

9.14 A single gene may affect many phenotypic characteristics

• A single gene may affect phenotype in many ways– This is called pleiotropy– The allele for sickle-cell disease is an example

Individual homozygousfor sickle-cell allele

Sickle-cell (abnormal) hemoglobin

Abnormal hemoglobin crystallizes,causing red blood cells to become sickle-shaped

Sickle cells

Breakdown of red blood cells

Clumping of cells and clogging of

small blood vesselsAccumulation of

sickled cells in spleen

Physical weakness Anemia Heart

failurePain and

feverBrain

damageDamage to

other organsSpleen damage

Kidney failureRheumatismPneumonia

and other infections

ParalysisImpaired mental

function

Figure 9.14

• Genetic testing can be of value to those at risk of developing a genetic disorder or of passing it on to offspring

Genetic testing to detect disease-causing alleles

Figure 9.15B

Figure 9.15A

• Dr. David Satcher, former U.S. surgeon general, pioneered screening for sickle-cell disease

• This situation creates a continuum of phenotypes– Example: skin color– Polygenic inheritance

A single characteristic may be influenced by many genes

Figure 9.16

P GENERATION

F1 GENERATION

F2 GENERATION

aabbcc(very light)

AABBCC(very dark)

AaBbCc AaBbCc

Eggs Sperm

Frac

tion

of p

opul

atio

n

Skin pigmentation

• Genes are located on chromosomes– Their behavior during meiosis accounts for

inheritance patterns

THE CHROMOSOMAL BASIS OF INHERITANCE

Chromosome behavior accounts for Mendel’s principles

• The chromosomal basis of Mendel’s principles

Figure 9.17

• Certain genes are linked– They tend to be inherited together because they

reside close together on the same chromosome

Genes on the same chromosome tend to be inherited together

Figure 9.18

• This produces gametes with recombinant chromosomes

• The fruit fly Drosophila melanogaster was used in the first experiments to demonstrate the effects of crossing over

Crossing over produces new combinations of alleles

A B

a b

Tetrad Crossing over

A B

a

ba

BA b

Gametes

Figure 9.19A, B

Figure 9.19C

• Crossing over is more likely to occur between genes that are farther apart– Recombination frequencies can be used to map the

relative positions of genes on chromosomes

9.20 Geneticists use crossover data to map genes

g

Figure 9.20B

Chromosome

c l

17%

9% 9.5%

• Alfred H. Sturtevant, seen here at a party with T. H. Morgan and his students, used recombination data from Morgan’s fruit fly crosses to map genes

Figure 9.20A

• A partial genetic map of a fruit fly chromosome

Figure 9.20C

Shortaristae

Blackbody(g)

Cinnabareyes(c)

Vestigialwings(l)

Browneyes

Long aristae(appendageson head)

Graybody(G)

Redeyes(C)

Normalwings(L)

Redeyes

Mutant phenotypes

Wild-type phenotypes

• A human male has one X chromosome and one Y chromosome

• A human female has two X chromosomes• Whether a sperm cell has an X or Y chromosome

determines the sex of the offspring

SEX CHROMOSOMES AND SEX-LINKED GENES

Chromosomes determine sex in many species

Figure 9.21A

X YMale

(male)

Parents’diploidcells

(female)

Sperm

Offspring(diploid)

Egg

• Other systems of sex determination exist in other animals and plants

Figure 9.21B-D

– The X-O system

– The Z-W system

– Chromosome number

• All genes on the sex chromosomes are said to be sex-linked– In many organisms, the X chromosome carries many

genes unrelated to sex– Fruit fly eye

color is a sex-linked characteristic

Sex-linked genes exhibit a unique pattern of inheritance

Figure 9.22A

– Their inheritance pattern reflects the fact that males have one X chromosome and females have two

Figure 9.22B-D

– These figures illustrate inheritance patterns for white eye color (r) in the fruit fly, an X-linked recessive trait

Female Male Female Male Female Male

XrYXRXR

XRXr

XRY

XR Xr

Y

XRXr

XR

Xr XRXR

XR

Y

XRY

XrXR XRY

XrY

XRXr

XR

Xr

Xr

YXRXr

XrXr XRYXrY

XrY

R = red-eye alleler = white-eye allele

• Most sex-linked human disorders are due to recessive alleles– Examples: hemophilia,

red-green color blindness– These are mostly seen in males– A male receives a single X-linked allele from his

mother, and will have the disorder, while a female has to receive the allele from both parents to be affected

Sex-linked disorders affect mostly males

Figure 9.23A

• A high incidence of hemophilia has plagued the royal families of Europe

Figure 9.23B

QueenVictoria

Albert

Alice Louis

Alexandra CzarNicholas IIof Russia

Alexis

DNA

• 1953 - James Watson, Francis Crick, Rosalind Franklin & Maurice Wilkins

• Lead to understanding of mutation and relationship between DNA and proteins at a molecular level

• 1959 – “Central Dogma”– DNARNAprotein

Genetic Concepts

• Chromosome – – double stranded DNA

molecule packaged by histone & scaffold proteins

DNA double helix

nucleosome

30nm fiber

condensed chromosome

Genetic Concepts

• Chromosome numbers– Constant for an organism– n - haploid number – 2n – diploid number

• Karyotype

Genetic Concepts

Y

Genetic Concepts

• Chromosome numbers– Each individual inherits n # of chromosomes from

dad & n # from mom– Humans - 46 chromosomes = 2n– Humans 23 paternal, 23 maternal– Humans n = ____– Each maternal & paternal pair represent

homologous chromosomes - called homologs

Genetic Concepts

(a) Chromosomal composition found in most female human cells (46 chromosomes)

(b) Chromosomal composition found in a human gamete (23 chromosomes)

1 2 3 4 5 6 7

XX

8

9 10 11 12 13 14 15

17 18 19 20 21 22

16

1 2 3 4 5 6 7

X

8

9 10 11 12 13 14 15

17 18 19 20 21 22

16

Diploid Haploid

Genetic Concepts• Homologous Chromosomes– Share centromere position– Share overall size– Contain identical gene sets at matching positions (loci)

gene for color

gene for shape

Genetic Concepts• Gene – sequence of DNA which is transcribed

into RNA – rRNA, tRNA or mRNA

• Locus – the position on a chromosome of a particular DNA sequence (gene)

G Locus – gene for color

W Locus – gene for shape

Genetic Concepts• DNA is mutable• A variation in DNA sequence at a locus is

called an allele– Diploid organisms contain 2 alleles of each locus

(gene)• Alleles can be identical – homozygous• Alleles can be different – heterozygous• If only one allele is present – hemizygous

– Case in males for genes on X and Y chromosomes

Genetic Concepts

Allele – G vs g; W vs w

At the G locus either the G or g allele may be present on a given homologue of a homologous pair of chromosomes

Genetic Concepts• Genome– Collection of all genetic material of organism

• Genotype– Set of alleles present in the genome of an organism

• Phenotype– Result of Gene Expression– Genes (DNA) are transcribed into RNA– mRNA is translated into protein, tRNA & rRNA work in

translation process– Biochemical properties of proteins, tRNAs & rRNAs

determine physical characteristics of organism

DNA

Gene

Transcription

Translation

RNA (messenger RNA)

Protein(sequence ofamino acids)

Functioning of proteins within livingcells influences an organism’s traits.

Gene Expression

Pigmentation gene,dark allele

Pigmentation gene,light allele

Transcriptionand translation

Highly functionalpigmentation enzyme

Poorly functionalpigmentation enzyme

Molecular level

Mutation & Phenotypic Variation

Wing cells

Lots of pigment made Little pigment made

Pigmentmolecule

(b) Cellular level

Pigmentation gene,dark allele

Pigmentation gene,light allele

Transcriptionand translation

Highly functionalpigmentation enzyme

Poorly functionalpigmentation enzyme

(a) Molecular level

Mutation & Phenotypic Variation

Dark butterfly Light butterfly Organismal level

Mutation & Phenotypic Variation

Dark butterflies are usuallyin forested regions.

Light butterflies are usually in unforested regions. Populational level