Module 1.

Basic genetic principles and technologies

Lecture 1.1 – Classical genetics and

its molecular mechanisms
What are major genetic questions?
• What is the material controlling our traits/performance?
• Why are we different?
• How is this material passed on?
Learning objectives
• Basic definitions in genetics
• Basic principles and terms in classical genetics
• Molecular mechanisms of classical genetics
• Chromosome crossover and its significance
Outline
• History and basic definitions in genetics
• Principles of inheritance
• Molecular mechanisms of inheritance
• Linkage and crossover
The two most famous biologists in history
Darwin

• Darwin’s “On the Origin of Species”

(1859)
• He believed that all living organisms
came from a common ancestor
• Evidences show that the 8 million living
species all evolved from a simple, single-
celled common ancestor around 3.5
Chimpanzee 98%
billion years ago
Monkey 95%
• Genomics also supports his theory as all Human DNA
kinds of organisms share a large Identical to Mouse 92%
proportion of common DNAs Fruit fly 36%
Banana 50%
7
Mendel
• Mendel discovered the principles of
inheritance
• Mendelian inheritance
• Proposed in 1865 and 1866
• 6-7 years after Darwin’s Theory of Evolution.
• Built the foundation of modern genetics
• Mendelian genetics is also called classical
genetics
• Mendel read Darwin's books, whereas all
available evidence indicates that Darwin knew
nothing of Mendel.
Definition of genetics
• Genetics is the study of genes, genetic variation, and
heredity in living organisms.
• Genes – the material controlling our traits/performance?
• genetic variation – Why are we different?
• heredity – how is this material passed on?
• It is a branch of biology.
• Genetics has many branches
Branches of genetics
• Behavioural genetics • Medical genetics
• Classical genetics • Microbial genetics
• Developmental genetics • Molecular genetics
• Conservation genetics • Quantitative genetics
• Ecological genetics • Population genetics
• Evolutionary genetics • Phylogenetics
• Genecology • Statistical genetics
• Genetic engineering • Genetic epidemiology
• Genomics • Archaeogenetics
• Human evolutionary genetics • Archaeogenetics of the Near East
• Human mitochondrial genetics • Psychiatric genetics
Why classical genetics still important?
• It explains how the genetic materials pass on from parents to
offspring
• It is the cornerstone of the modern genetics, including
genomics
• Classical and modern genetics are to answer the same
questions, but using different approaches.
• Modern genetics explored new ways to answer old questions
• Some genetic studies still rely on classical genetic approaches
• Classical genetics directly works on trait; modern genetics works on genes or
genetic markers
• If a trait is controlled by many genes, it is simpler to work on the trait
The definitions of gene and allele
• Gene is an evolving definition
• It was first defined as an “unit of inheritance”
• Not defined by Mendel, but 10 years later by someone else
• Then defined as a small section of a chromosome after
chromosomes were discovered
• Now defined as a linear segment in the DNA molecule that
encodes a protein
• Alleles are defined as different versions of a gene
Gene vs. allele

Gene Allele

Definition A section of DNA that A specific variation of a

controls a certain trait gene
Examples A gene for eye color A allele for blue eyes or green
eyes
Tree crown form Wide crown, narrow crown
Locus/loci Two alleles at a locus (mostly)
Genotype vs. phenotype

Genotype Phenotype

Definition A specific combination of The physical appearance

alleles for a given gene of the genotype
Example
BB, Bb or bb Blue eyes or brown eyes

Genotype is also referred to A phenotype also called

as overall genetic makeup of a trait
an organism
Outline
• History and basic definitions in genetics
• Principles of inheritance
• Molecular mechanisms of inheritance
• Linkage and crossover
 The core of classical genetics
• To study the inheritance of genes from parents to children (offspring)
• Before Mendelian genetics, it was believed that the genetic materials
from the two parents were mixed up, then pass to offspring –
Blending inheritance
• Mendel discovered the inheritance and summarized it into three laws
of inheritance
• Law of Segregation (First Law)
• Law of Dominance (Third Law)
• Law of Independent Assortment (Second Law)
Mendel‘s “First Law” of Inheritance
(one gene – one trait)
Law of Segregation

Phenotypes: 3 : 1
Mendel‘s “First Law” of Inheritance
(one gene – one trait)

• Law of Segregation
• Each parent has two alleles for each trait
(a gene) and only one allele randomly
passes on to an offspring

Selfing

Phenotypes: 3 : 1
Genotypes: 1WW: 2Ww: 1ww
Dominance (the “Third Law”)
• Mendel’s Third Law - for the two alleles
of a gene, the recessive allele will
always be masked by the dominant
allele
• Dominance makes phenotypes not
always showing genotypes
• Homozygous – a genotype with the
same alleles at a gene
• showing the genotype
Homozygote Heterozygote
• Heterozygous – a genotype with
different alleles at a gene
• not showing the genotype
Test cross
• Test cross is used to reveal the genotype of an individual
• In a test cross, an individual in question (WW, Ww or ww?)
is bred with an recessive homozygous individual for the
trait (ww)
Codominance
• Codominance is a form of inheritance
wherein the alleles of a gene in a
heterozygote are fully expressed
• The phenotype of the offspring is a
combination of the phenotype of the
parents
• E.g., type AB blood in humans
• This was not discovered by Mendel
www.teeturtle.com
Codominance in Sitka spruce

Green Green All green

Green Red
All reddish green

Codominant: the heterozygote show intermediate phenotype

Exercises

Round leaf Cut leaf

Leaf phenotypes in European beech, a trait

controlled by a single gene
Assuming the two individuals are homozygotes,
how can you figure out if the allele for the cut leaf
phenotype is dominant, recessive or codominant?
 ×

Round Cut

Round dominant
 ×

Round Cut

Cut dominant
 ×

Round Cut

Codominant
 ×

LL ll

Ll

The fact is the round leaf being dominant

 ×

Ll
Ll

L l

L LL Ll A Punnett square

l Ll ll

Genotype: ? LL: ? Ll: ? ll

Phenotype: ? round: ? cut
 ×

?? ll

39 43
• Albinism is caused
by a recessive and
lethal allele
• Seedlings with
albinism has no
chlorophyll, thus no
photosynthesis
• How come tree
populations still
carry this allele?
Albinism is in low frequency, but it occurs in many
species including human.
In US, for example, the incidence is 1 in 17,000, but the
frequency of albinism carrier is much higher, 1 in 70.
Why the two ratios are so different?
Kermode bear

• Kermode bear’s phenotype is

determined by a recessive allele of a
single gene
• B – black allele
• b – white
• What is the genotype of the baby bear?

• What is the genotype of the mother?

• What are the possible genotypes of the

father?
 Terms
• Gene and allele, locus and loci
• Genotype and phenotype/trait
• Dominance, recessive and codominance
• Homozygous and heterozygous
• Test cross
Questions
Mendel's "Second Law" of Inheritance
(two genes – two traits)
• Law of Independent Assortment

Self fertilization
Mendel's "Second Law" of Inheritance
• Law of Independent
Assortment
• Different pairs of alleles
are passed to offspring
independently of each
other

Pods: 12 Seeds: 12
4 4
Questions
• Break for 5 min
Outline
• History and basic definitions in genetics
• Principles of inheritance
• Molecular mechanisms of inheritance
• Linkage and crossover
Timeline of inheritance discoveries
• 1865 - Mendel’s laws of inheritance
• 1869 - DNA Isolated
• 1902 - Sutton found that the
segregation of chromosomes during Walter Sutton
meiosis matched the segregation
pattern of Mendel’s laws
• 1915 - Morgan found that
chromosomes carry genes, and also
discover genetic linkage, won Nobel
Prize in 1933.
Chromosomes
• A chromosome is a DNA molecule
with part or all of the genetic
material of an organism
• We will only cover the inheritance of
chromosomes here and leave
detailed molecular features about
DNA and chromosome to next
lecture
Homologous chromosomes
• Chromosomes are in pairs except in
gametes (sperms or eggs)

• Each pair of chromosomes are called

homologous chromosomes, Human chromosomes
• one from the mother and another from the
father
• Each pair have the same genes (except
allelic variation)
Chromosome replication – meiosis
• Meiosis is part of a
reproductive process
• In this process, a cell
divides twice to produce
4 daughter cells –
gametes (eggs or sperms)
• The new cells have half
number of chromosomes
of the mother cell
• Homologous
chromosomes exchange Crossovers occur
materials – crossover
• the chromosomes are no https://www.youtube.com/watch?v=MNq015d03MU
longer the same as they
were from their patents
Molecular genetics confirmed classical genetics – First Law
• Mendel’s Frist Law: each parent has two
alleles for a trait and only one of them
randomly passes on to an offspring
• Molecular gen: the two alleles are located on
a pair of homologous chromosomes. One
from the mother and one from the father
• The First Law helped to figure out the
genetic feature of chromosomes, while the
discovery of chromosomes confirms the First
Law
• New by molecular genetics: crossovers occur
during meiosis that mix information between
the two homologous chromosomes
Molecular genetics confirmed classical genetics – Second Law
• Second Law – the law of independent
assortment
• Different pairs of genes are passed to offspring
independently of each other
• Molecular gen: During meiosis, different
chromosome are replicated and segregated
independently
• It confirms that a pair of genes located on
different chromosomes follow the Second Law
• New by molecular gen: A pair of genes
located on the same chromosomes may or
may not follow the Second Law
• due to crossover
Molecular genetics confirmed classical genetics – Third Law

• Third Law – dominance

• Recessive alleles are masked by dominant alleles
• Molecular mechanisms:
• The recessive allele may not be transcribed
• Transcribed but with a slightly different function
• New by molecular genetics:
• Dominance can be relative to the another allele
• Codominance are common
• Quantitative traits are controlled by multiple codominant
genes
Outline
• History and basic definitions in genetics
• Principles of inheritance
• Molecular mechanisms of inheritance
• Linkage and crossover
Linkage and crossover
• The law of the independent assortment was
derived based on genes located on different
chromosomes. These genes segregate
independently during meiosis.
• Genes located on the same chromosome may not
stay together due to crossover between
homologous chromosomes
• When genes are linked, we call them in linkage
disequilibrium (LD, in probability)
 Genetic mapping based on LD
Independent assortment Genes linked
• If two genes are not
lined, they follow the
independent assortment
• If two gene are linked,
the rate of
recombination is used to
estimate the distance
between the two genes
• With the relative
distances, a genetic map
can be constructed Construct
genetic maps
Estimate the distance
on a chromosome
What is the chance for a couple to have two genetically
identical children?
• 2 pairs of chromosomes -> 4
combinations
• 23 pairs in human, How many
combinations?
• = 2^23 = 8,324,608
• Crossovers also add many more
possibilities
• So, almost no chance for a couple to
have 2 genetically identical children
 Learning objectives
• Basic definitions in genetics
• Basic principles and terms in classical genetics
• Molecular mechanisms of classical genetics
• Chromosome crossover and its significance