Genetics

The scientific analysis of

inherited variation

Genetics: the study of inherited variation

Gregor Mendel began

the formal study of

genetics.

In 1866 he published

his results: inherited

factors are passed

down unchanged

from one generation

to the next (no

blending or other

modification)

Genetics: the study of inherited variation

Gregor Mendel developed

methods that are still used

today

• controlled crosses with

pure breeding lines

• followed traits for

multiple generations

• counted progeny

• developed, tested

hypotheses

Modern Genetic Analysis Includes

Two Principal Components

• Classical or Mendelian Genetics – Inheritance patterns, transmission of genes

– Studied by making controlled crosses

– Genes identified by heritable phenotypic variation

• Molecular and Biochemical Genetics – The structure, function and regulation of

genes

– Studied by manipulating, analyzing DNA, RNA and proteins

– Genes identified by molecular variation

Modern Genetics Combines

Mendelian and Molecular Genetics

+ Reverse Genetics

Organisms are made of cells. Each cell contains

chromosomes. Chromosomes carry genes.

The organization of living things is based on

cells and directed by genes:

Living things have many different

chromosome structures and organizations

DNA is a double helix:

• two strands of

nucleotides

• held to each other by

hydrogen bonds

• pairing = – Adenine - Thymine

– Guanine - Cytosine

One AT or GC pair = one

base pair

The length of DNA is

measured in base pairs or

bp. 1,000 bp = 1kb

8 bp

A closer look at DNA

DNA Replication: Semiconservative Normal replication – faithful due to complementary pairing

Mutation – replication error modifies DNA sequence

DNA replication is the

molecular basis for

chromosomal replication

• DNA replication

two identical daughter

chromosomes

• passed on to the next

generation.

• The only difference

between daughters is

due to rare mutations

Meiosis:

haploid

germline

cells

Mitosis:

diploid

somatic

cells

Germline

mutation:

may be

passed to

offspring

Somatic

mutation:

not

passed to

offspring

DNA replication is the core of cell reproduction

Genetic distance

estimated from

(cytochrome c)

DNA

DNA Ancestry

20 generations = 1,048,576 ancestors

From Genes to Phenotype: Information from DNA is used to

synthesize enzymes that catalyze

biological chemical reactions.

transcription translation

DNA RNA protein

phenotype

Transcription in a eukaryote

Figure 1-5 part 2

Gene transcription is controlled by a promoter

• RNA polymerase binds to promotor to

initiate transcription

• Promoter open – transcription on

• Promoter blocked – transcription off

The Biochemical Mechanism for

Transcription

Transcription in a eukaryote - RNA processing

• Introns are removed

• Exons are spliced

Transcription and translation in a eukaryote

Translation

Amino acid sequence of a

protein determines its folding

pattern and activity

Genomes • Genome

– entire haploid genetic content of an organism

– usually measured in kilobase pairs (kb) or

megabase pairs (mb)

– human haploid genome ≈ 3,000,000 kb

• Coding Genome

– DNA that codes for protein (< 2% of human

genome)

• Noncoding Genome – everything else

– DNA involved in gene regulation or with no

known function (introns, for example)

Genomic Structure in Different Organisms:

simpler organisms have relatively more coding

DNA and less noncoding DNA

13 genes / 20 kb

11 genes / 20 kb

0.8 genes / 20 kb

0.33 genes / 20 kb

Total coding DNA per segment

Albinism: A mutant gene

nonfunctioning

enzyme

prevents melanin

synthesis

causes albinism

Pigmentation results from two properly functioning genes

One malfunctioning gene does not change pigmentation

Two malfunctioning genes leads to albinism

DNA can be

analyzed with gel

electrophoresis

See Genetics Links, Interactive Animation of Gel Electrophoresis

DNA is

separated by

size during

electrophoresis

DNA on a gel may be

visualized by staining

enzymes cut at

specific 6 base

sequence

every 46 = 4,096

bp on average

Fragments of DNA to be analyzed by electrophoresis can be

obtained by cutting DNA with restriction enzymes

A probe can be used to detect specific

DNA fragments or chromosomal regions

Probes can be used to detect specific macromolecules

Figure 1-12 part 2

Probes can be used to detect specific macromolecules

Figure 1-12 part 3

Probes can be used to detect specific macromolecules

Figure 1-12 part 4

Polymerase Chain Reaction can be used to obtain specific DNA for analysis

Polymerase Chain Reaction

Polymerase Chain Reaction (PCR) - YouTube

Model Organisms in Genetics

Application of animal models -

human medical and

developmental genetics:

• human genes often resemble those of other modern animals because humans share a common ancestor with them

Application of animal models to

human developmental genetics:

extensive knowledge about human genes has been derived from the study of model organisms –

HOX genes regulate developement, control segment ID

Examples from Medical Research:

• nematode worm – drug development

• one third of the worm's ~5,800 proteins are

similar to mammalian proteins

• yeast – molecular cancer research

• 38% of yeast’s 2,300 proteins are similar to

those of mammals

• fruit flies

• 75% of known human disease genes have

equivalents in fruit flies

• p53 gene in both plays a role in cell death

and uncontrolled growth

Genetics: Study of Inherited Variation

• Wildtype – the common, typical phenotype

• Mutation

– Rare in population, usually harmful

– Usually discrete phenotype (albinism)

• Polymorphism – more than one wildtype

– Natural variation, common in population

– May be discrete

• Easily identifiable phenotypic categories

– Or continuous

• Phenotypic categories indistinct

Types of Phenotypic Variation

Phenotypic Variation:

Wildtype vs. Mutation

Manx cat:

dominant mutation

There is a

broad

fascination

with mutants

and odd

hybrids

Scientists successfully create human-bear-pig

chimera (manbearpig) posted April 1, 2008, Thinkgene.com

http://www.thinkgene.com/scientists-successfully-create-human-bear-pig-chimera

Developmental Mutants: HOX genes

Phenotypic Variation:

Discrete Wildtype Polymorphism

Other discrete polymorphisms in nature

Continuous Phenotypic Variation:

a common form of polymorphism

Mutation, discrete

polymorphism or

extremes of continuous

variation?

Sultan Kösen

He Pingping

Svetlana Pankratova

8’ 3”

2’ 5”

Sources of Phenotypic Variation Genetic and non-genetic factors may affect

phenotypic expression

• Genes only – no known environmental effects

― Human examples – eye color, blood type

• Environment only – no known genetic effects

— Human example – language and culture

• Both genetic and environmental effects

(Genotype X Environment Interaction)

— Human examples

• Developmental

Eye Facets

(ommatidia)

Bristles Some Fruitfly Anatomy

Environment

plays a role in

the expression

of wildtype eye

alleles.

Eye Shape Mutants

An example of

interaction

between

genotype and

environment

• Curly wing mutation in Drosophila

– expression depends on temperature

during development

• 250C Cy mutant = curly wings

• 180C Cy mutant = normal wings

• Sickle cell anemia

– expression depends on oxygen tension in

blood, low O2 → sickling

• Type II Diabetes

– usually adult onset

– affected by diet, exercise

Other Examples of Genotype X

Environment Interaction

Polypterus (“dragonfish”)

aquatic and

terrestrial

rearing on land

alters anatomy and

behavior to facilitate

terrestrial locomotion

Genotype X Environment Interaction

• Expression of genotype depends at least partly

on environmental conditions

• Neither genotype nor environment alone are

sufficient to explain phenotype - both must be

known • (Like the length and width must both be known to

calculate the area of a rectangle)

• Norm of reaction = range of phenotypic

expression of a genotype over different

environments

Norm of reaction

for bristle number:

different colored

lines represent

different inbred

homozygous

strains

Effect of

environment varies

among genotypes

Effects of environment differ among

genotypes:

Different

growing

environments

have different

affects on

different

genotypes

Genotype X Environment Interactions:

Implications for Selective Breeding

In all populations (plant,

animal, domestic, wild)

many characters: – vary continuously

– multiple genes contribute

– are subject to G X E

interactions

Selective Breeding

Selective breeding occurs

when only relatively

extreme phenotypes are

used for the next

generation

Selective breeding has been important for

• modification of domestic plants and animals

• demonstration of genetic basis for variation in

specific traits

Genotype X Environment Interactions:

Implications for Selective Breeding

• Phenotypic variation is the basis for

selective breeding

• Genetic variation is the basis for successful

selective breeding

Selective breeding over

several generations

can shift the phenotypic

distribution of a

population

Selective Breeding

Genotype X Environment Interactions:

Implications for Selective Breeding

Genetic variation

determines the response to

selective breeding:

Traits with greater genetic

variation evolve more

rapidly under selective

breeding

Variation due to

environmental factors does

not respond to selection

Response to selective

breeding demonstrates

presence of genetic

variation

Selective breeding can produce dramatic

changes over many generations:

flight speed of fruit flies in a wind tunnel

Heritable traits can respond to selection in

either direction – increase or decrease in

trait expression

Domestic dogs originated

with a wild species

Some retain

substantial similarity

to the ancestral

species

Selective breeding has

produced some extreme

varieties of domestic

animals and plants.

Voluntary wheel walking in mice:

selective breeding can reveal a

genetic component to behavior

Maze running

ability in rats: a

cognitive trait that

can be altered by

selection

Rearing Conditions Alter the Phenotypes of

Selected Maze Bright and Maze Dull lines

Rearing Conditions

Restricted Normal Enriched

Nu

mb

er

of

Mis

takes

80

100

120

140

160

180

Bright

Dull

Heritability of Phenotypic Variation

• Heritability is the proportion of phenotypic

variation in a population that is attributable

to genes

• Genes only – no environmental effects

― Heritability of trait is 100% = 1.0

• Environment only – no genetic effects

— Heritability of trait = 0

• Genetic and environmental effects

— Heritability > 0 and < 1.0

• Higher heritability = greater likelihood of a

phenotype being transmitted faithfully,

greater response to selective breeding

Heritability is

often expressed

as a range and

can differ

widely for

different traits

Summary

• Agricultural plants, animals and laboratory

model organisms respond to selective

breeding:

– The response is repeatable, can be extended over

many generations and can result in a phenotype far

outside the range of normal variation

• Many complex traits respond to selective

breeding:

– Anatomical, physiological, behavioral

• Genetic variation contributes to variation in the

expression of complex traits

• Heritability is a measure of the extent to which

variation in a population is due to genes

Human heritability: comparisons of

monozygotic (MZ) and dizygotic (DZ) twins

• MZ twins reared apart –

– Genetically identical, reared in different

environments

– Greater similarity between members of the

pairs = higher heritability

• DZ and MZ twins reared in birth families

– Rearing environment is the same for both

members of all pairs

– Greater similarity between MZ than DZ pairs

= higher heritability

Measurements of identical twins reared apart permit estimates of heritability for human traits:

Correlation between members of the twin pair over many pairs provides the heritability for the trait

fingerprint ridge count 0.97

height 0.85

IQ 0.5 - 0.7

scholastic achievement 0.40

good memory 0.20

Heritability of Some Common Traits

Heritability of IQ is altered by

environmental factors: (based on MZ-DZ birth family comparisons)

Middle Income +

nutrition, healthy 0.74

Poverty (< $10,000/year)

nutrition, other

marginal health 0.39

achievement (works hard, strives

for mastery) 0.38

social closeness (intimacy) 0.15

stress reaction (neuroticism) 0.48

aggression 0.67

absorption (imagination) 0.74

Human Personality Traits Show a

Range of Heritability

Summary

• Genes do not “determine” phenotype

but set limits on variation − Norm of Reaction

• High heritability ≈ narrower limits

• Low heritability ≈ broader limits

• Individuals may be strongly or weakly

predisposed to specific phenotypes. − Environment plays a role in most traits

− Human microbiome - environmental

affects on many physiological traits