IGA 8e

1
(No Transcript)
2
Mendelian and Molecular Genetics

• Dr. Fernand Gauthier
• 3321 Biosciences Complex
• 533-6000 ext. 77661
• Office Hours
• Drop-in (Mon-Thurs 10-12 3-4)
• or by Appointment

3
Mendelian and Molecular Genetics

• Textbook
• GENETICS Analysis Principles. Brooker, R.,
  2005. 2nd Ed.
• Readings will be assigned throughout the term
• Course Website
• http//seroudelab.biology.queensu.ca16080/Bio205/

4
Mendelian and Molecular Genetics

• Lectures
• Labs Start Sept 10
• Biosciences Complex 3312/3319/3326
• Lab Manuals Available at Bookstore

5
Mendelian and Molecular Genetics

• Mark Breakdown
• Midterm October 23rd closed book 15
• Final Exam open book 45
• Lab 3 reports and 5 quizzesReport 1 Oct
  29-Nov 2 15Report 2 Nov 12-16 10
• Report 3 Nov 26-30 5
• Quizzes 2 each

6
(No Transcript)
7
(No Transcript)
8
Course Overview

• What is the hereditary material?
• What is DNA?
• How is DNA copied?
• What are genes?
• How do genes work
• How can we manipulate DNA and genes?

9
The relationship between genes and traits

• Genetics is the study of heredity and variation
• It is the unifying discipline in biology
• The central theme in genetics is the gene
• The gene may be defined as a unit of heredity
• Genes provide the blueprint that determines the
  traits of an organism

10
The Molecular Expression of Genes Within Cells
Leads to an Organisms Outwardly Visible Traits

• A trait or phenotype is any characteristic that
  an organism displays
• There are several types of traits
• Morphological traits
• Affect the appearance of the organism
• Example The color of a flower
• Physiological traits
• Affect the function of the organism
• Example Ability to metabolize a sugar
• Behavioral traits
• Affect the behaviour of the organism
• Example circadian rhythm

11
The examination of the composition of living
organisms is necessary to understand the
relationship between genes and phenotype

• All cells are constructed from small organic
  molecules
• These are linked together by chemical bonds to
  form larger molecules
• Cells contain four main types of large molecules
• Nucleic acids
• Proteins
• Carbohydrates
• Lipids

12
The examination of the composition of living
organisms is necessary to understand the
relationship between genes and phenotype

• Nucleic acids, proteins and carbohydrates are
  termed macromolecules
• They are polymers constructed from smaller
  molecules called monomers
• Cellular structures form as a result of the
  interaction of molecules and macromolecules

13
Each cell contains many different proteins that
determine cellular structure and function

• The characteristics of a cell largely depend on
  the proteins it produces
• Proteins are the workhorses of cells
• They have diverse biological functions

14
Each cell contains many different proteins that
determine cellular structure and function

• Structural proteins
• Tubulin
• Aggregates to form microtubules
• Plays role in cell shape and movement
• Contractile proteins
• Myosin
• Plays role in muscle contraction
• Hormonal proteins
• Insulin
• Regulates the level of glucose in the blood

15
Each cell contains many different proteins that
determine cellular structure and function

• A particularly important group of proteins are
  the enzymes
• Enzymes are biological catalysts
• Catabolic enzymes
• Involved in the breakdown of large molecules into
  smaller ones
• Provide energy for the activities of the cell
• Anabolic enzymes
• Involved in the synthesis of large molecules from
  smaller ones
• Provide components for the construction of the
  cell

16
DNA Stores the Information for Protein Synthesis

• The genetic material in living organisms is
  deoxyribonucleic acid (DNA)
• DNA encodes the information required to
  synthesize all cellular proteins
• It is able to do so because of its molecular
  structure

17
DNA Stores the Information for Protein Synthesis

• DNA is a polymer of nucleotides
• Each nucleotide contains one nitrogenous base
• Adenine (A)
• Thymine (T)
• Cytosine (C)
• Guanine (G)
• The genetic information is stored in the linear
  sequence of these bases along the DNA molecule

18
DNA Stores the Information for Protein Synthesis

• For example
• ATG GGC CTT AGC DNA Sequence
• Met Gly Leu Ser Protein Sequence
• TTT AAG CTT GCC DNA Sequence
• Phe Lys Leu Ala Protein Sequence

19

• The DNA in living cells is contained within large
  structures termed chromosomes

• Each chromosome is a complex of DNA and proteins
• An average human chromosome contains
• More than a 100 million nucleotides
• 1000-2000 genes

20

• For a given species, cells have a fixed number of
  chromosomes

• Human somatic cells
• have 46 chromosomes
• have 23 homologous pairs
• are diploid (2n)
• Total DNA, set of chromosomes genome
• Diploid genome

21

• For a given species, cells have a fixed number of
  chromosomes

• Human germinal cells (gametessperm and egg
  cells)
• have 23 chromosomes
• are haploid (1n)
• Haploid genome
• The union of sperm and egg during fertilization
  restores the diploid number

22
The information within the DNA is accessed during
the process of gene expression

• Gene expression occurs in two steps
• Transcription
• The genetic information in DNA is copied into a
  nucleotide sequence of ribonucleic acid (RNA)
• Translation
• The nucleotide sequence in RNA is converted
  (using the genetic code) into the amino acid
  sequence of a protein

23
Figure 1.6
24

• Traits are controlled, at least in part, by genes
  
• The relationship between genes and traits spans
  four levels of biological organization
• 1. Genes are expressed at the molecular level
• 2. Proteins function at the cellular level
• 3. Traits are observed at the organismal level
• 4. Genes/traits within a particular species can
  also be studied at the populational level

25
a. Molecular level
b. Cellular level
c. Organismal level
d. Populational level
26
Inherited Differences in Traits Are Due to
Genetic Variation

• Genetic variation refers to differences in
  inherited traits among individuals within a
  population
• For example In petunias, white vs. purple
  flowers
• In some cases, genetic variation is very striking
• Members of the same species may be misidentified
  as belonging to different species. e.g. Broccoli
  and cauliflower are two kinds of Brassica
  oleracea
• Genetic variation is the fuel of evolution
• Members of a species compete for essential
  resources
• In some individuals, random mutations lead to
  beneficial alleles
• Individuals are better adapted to the environment
• These individuals are more likely to survive and
  reproduce
• Therefore, the beneficial alleles are passed on
  to subsequent generations

27

• Genetic variation is a result of various types of
  changes at the molecular level
• 1. Gene mutations
• Small differences in gene sequences
• Lead to a different version (allele) of the same
  gene
• 2. Changes in chromosome structure
• Large segments of the chromosome may be lost or
  duplicated
• 3. Changes in chromosome number
• Single chromosomes may be lost or gained
• A whole set of chromosomes may be inherited

28
Traits are also influenced by the environment

• The traits an individual expresses often do not
  result from its genes alone
• Rather, traits are a result of the interaction
  between genes and the environment
• For example, an individuals diet has an effect
  on his/her height and weight
• In some cases, the environment dictates whether a
  disease is manifested in an individual or not

29
FIELDS OF GENETICS

• Genetics encompasses many biological disciplines
• Molecular biology / Biochemistry / Biophysics
• Cell biology
• Microbiology
• Mathematics
• Medicine
• Population biology
• It is traditionally divided into three areas
• Transmission genetics
• Molecular Genetics
• Population Genetics

30
Transmission Genetics Explores the Inheritance
Patterns of Traits as They Are Passed from
Parents to Offspring

• Transmission genetics is the oldest field of
  genetics
• It examines how traits are passed from one
  generation to the next

31
Transmission Genetics Explores the Inheritance
Patterns of Traits as They Are Passed from
Parents to Offspring

• The conceptual framework was provided by Gregor
  Mendel in the 1860s (http//www.mendelweb.org/Mend
  el.html)
• Genetic determinants pass from parent to
  offspring as discrete units
• These are now termed genes

32
Molecular Genetics Seeks a Biochemical
Understanding of the Hereditary Material

• Molecular genetics is the most modern field of
  genetics
• It deals with the gene itself
• Its features, organization and function
• Molecular geneticists study model organisms
• The genes found in these organisms behave
  similarly as those in humans
• They study mutant genes that have an abnormal
  function
• Example Loss-of-function mutation

33

• Molecular genetics is covered in
• Chapters 9-15
• Structure, replication, expression and regulation
  of the genetic material
• Chapter 16
• Mutations and rearrangements of the genetic
  material
• Chapters 18
• Recombinant DNA technology and computer-based
  approaches to studying the genetic material

34
Population Genetics Is Concerned With Genetic
Variation and Its Role in Evolution

• Population genetics deals with the genetic
  composition of populations and how it changes
  over time and space
• It connects the work of Mendel on inheritance to
  that of Darwin on evolution
• Population genetics is covered in Biol-206

35
2
Mendelian inheritance
36
Key questions

• How is it possible to tell if a phenotype has a
  genetic basis?
• What is the explanation for the patterns by which
  phenotypes are inherited?
• Is the pattern for one phenotype independent of
  that for other phenotypes?
• Is the pattern of inheritance influenced by the
  location of genes in the genome?

37
Outline

• Introduction
• Autosomal inheritance
• Single trait inheritance
• Predicting inheritance
• Two traits inheritance
• Cellular and molecular basis
• X-linked inheritance

38
INTRODUCTION

• Many theories of inheritance have been proposed
  to explain transmission of hereditary traits
• Theory of Pangenesis
• Theory of Preformationism
• Blending Theory of Inheritance

39
INTRODUCTION

• Theory of pangenesis
• Proposed by Hippocrates (ca. 400 B.C.)
• Seeds are produced by all parts of the body
• Collected in the reproductive organs
• Then transmitted to offspring at moment of
  conception

40
INTRODUCTION

• Theory of preformationism
• The organism is contained in one of the sex cells
  as a fully developed homunculus
• Miniature human
• With proper nourishment the homunculus unfolds
  into its adult proportions
• The Spermists believed the homunculus was found
  in the sperm
• The Ovists believed the homunculus resided in
  the egg

41
INTRODUCTION

• Blending theory of inheritance
• Factors that control hereditary traits are
  maleable
• They can blend together generation after
  generation

42
INTRODUCTION

• Gregor Mendels pioneering experiments with
  garden peas refuted all of the above!

43
Autosomal inheritance Mendel laws

• Gregor Johann Mendel (1822-1884) is considered
  the father of genetics
• Mendel was an Austrian monk
• His success can be attributed, in part, to
• His boyhood experience in grafting trees
• This taught him the importance of precision and
  attention to detail
• His university experience in physics and natural
  history
• This taught him to view the world as an orderly
  place governed by natural laws
• These laws can be stated mathematically

44
Autosomal inheritance Mendel laws

• He conducted his landmark studies in a small 115-
  by 23-foot plot in the garden of his monastery
• From 1856-1864, he performed thousands of crosses
• He kept meticulously accurate records that
  included quantitative analysis

45
Autosomal inheritance Mendel laws

• His work, entitled Experiments on Plant Hybrids
  was published in 1866
• http//www.mendelweb.org/Mendel.plain.html
• It was ignored for 34 years
• Probably because
• It was published in an obscure journal
• Lack of understanding of chromosome transmission

46
Autosomal inheritance Mendel laws

• In 1900, Mendels work was rediscovered by three
  botanists working independently
• Hugo de Vries of Holland
• Carl Correns of Germany
• Erich von Tschermak of Austria

47
Definitions

• Hybridization
• The mating or crossing between two individuals
  that have different characteristics
• Purple-flowered plant X white-flowered plant
• Hybrids
• The offspring that result from such a mating

48
Mendels Experiments in Plant Hybridization (1865)

• What is the purpose of Mendels Experiment?
• What biological question was he attempting to
  answer?

49
Mendels Experiments in Plant Hybridization (1865)

• What is the purpose of Mendels Experiment?
• What biological question was he attempting to
  answer?
• 1 Introductory Remarks
• (mid 2nd par) That, so far, no generally
  applicable law governing the formation and
  development of hybrids has been successfully
  formulated can hardly be wondered at by anyone
  who is acquainted with the extent of the task,
  and can appreciate the difficulties with which
  experiments of this class have to contend.
• (3rd par) Those who survey the work done in this
  department will arrive at the conviction that
  among all the numerous experiments made, not one
  has been carried out to such an extent and in
  such a way as to make it possible to determine
  the number of different forms under which the
  offspring of the hybrids appear, or to arrange
  these forms with certainty according to their
  separate generations, or definitely to ascertain
  their statistical relations.
• 3 Division and Arrangement of the Experiments
• (mid 1st par) The object of the experiment was to
  observe these variations in the case of each pair
  of differentiating characters, and to deduce the
  law according to which they appear in successive
  generations.

50
Mendels Experiments

• Mendel did not have a hypothesis to explain the
  formation of hybrids
• Rather, he believed that a quantitative analysis
  of crosses may provide a mathematical
  relationship
• Thus, he used the empirical approach
• And tried to deduce empirical laws

51
Mendel Chose Pea Plants as His Experimental
Organism

• Mendel chose the garden pea (Pisum sativum) to
  study the natural laws governing plants hybrids
• The garden pea was advantageous because
• 1. It existed in several varieties with distinct
  characteristics
• 2. Its structure allowed for easy crosses

52
Mendel Chose Pea Plants as His Experimental
Organism

• Mendel carried out two types of crosses
• 1. Self-fertilization
• Pollen and egg are derived from the same plant
• 2. Cross-fertilization
• Pollen and egg are derived from different plants

53
(No Transcript)
54
More definitions

• A specific characteristic of an organism is
  termed character or trait or phenotype
• A variety that produces the same trait over and
  over again is termed a true-breeder

55
Single trait inheritance

• Mendel crossed two variants that differ in only
  one trait
• The offspring of these crosses are termed hybrids
• Crossing these hybrid offspring is termed a
  monohybrid cross

56
Division and Arrangement of the
ExperimentsMendel Studied Seven Traits That
Bred True
57
4 The Forms of the Hybrids (2nd par) In the
case of each of the 7 crosses the
hybrid-character resembles that of one of the
parental forms so closely that the other either
escapes observation completely or cannot be
detected with certainty. those characters
which are transmitted entire, or almost unchanged
in the hybridization,, are termed the dominant,
and those which become latent in the process
recessive.
58
5 The First Generation From the Hybrids
MONOHYBRID CROSSES
59
Interpreting the Data

• For all seven traits studied
• 1. The F1 generation showed only one of the two
  parental traits
• 2. The F2 generation showed 31 ratio of the
  two parental traits
• These results refuted a blending mechanism of
  heredity

60
Interpreting the Data

• Indeed, the data suggested a particulate theory
  of inheritance
• Mendel postulated the following

61
First Mendel Law

• 1. A pea plant contains two discrete hereditary
  factors, one from each parent
• 2. The two factors may be identical or different
• 3. When the two factors of a single trait are
  different
• One is dominant and its effect can be seen
  (Capitalized symbol)
• The other is recessive and is not expressed (all
  lower case symbol)
• 4. During gamete formation, the paired factors
  segregate randomly so that half of the gametes
  received one factor and half of the gametes
  received the other
• This is Mendels Law of Segregation

62
More definitions

• Mendelian factors are now called genes
• Alleles are different versions of the same gene
• An individual with two identical alleles is
  termed homozygous
• An individual with two different alleles, is
  termed heterozygous
• Genotype refers to the specific allelic
  composition of an individual
• Phenotype refers to the outward appearance of an
  individual

63
(No Transcript)
64
Predicting cross outcomes

• A Punnett square is a grid that enables one to
  predict the outcome of simple genetic crosses
• It was proposed by the English geneticist,
  Reginald Punnett
• We will illustrate the Punnett square approach
  using the cross of heterozygous tall plants as an
  example

65
Punnett Squares

• 1. Write down the genotypes of both parents
• Male parent Tt
• Female parent Tt
• 2. Write down the possible gametes each parent
  can make.
• Male gametes T or t
• Female gametes T or t

66

• 3. Create an empty Punnett square

• 4. Fill in the Punnett square with the possible
  genotypes of the offspring

67

• 5. Determine the relative proportions of
  genotypes and phenotypes of the offspring

(0.5)
(0.5)
(0.5)
Tall
Tall
(0.5)
dwarf
Tall
68

• 5. Determine the relative proportions of
  genotypes and phenotypes of the offspring

(0.5)
(0.5)
(0.5)
(0.25)
(0.25)
Tall
Tall
(0.25)
(0.5)
(0.25)
dwarf
Tall
69

• 5. Determine the relative proportions of
  genotypes and phenotypes of the offspring
• Genotypic ratio
• TT Tt tt
• 1 2 1
• Phenotypic ratio
• Tall dwarf
• 3 1

(0.5)
(0.5)
(0.5)
(0.25)
(0.25)
Tall
Tall
(0.25)
(0.5)
(0.25)
dwarf
Tall
70
Two traits inheritance

• Mendel also performed a dihybrid cross
• Crossing individual plants that differ in two
  traits
• For example
• Trait 1 Seed texture (round vs. wrinkled)
• Trait 2 Seed color (yellow vs. green)
• There are two possible patterns of inheritance
  for these traits

71
(No Transcript)
72
(No Transcript)
73
(No Transcript)
74
8 The Offspring of Hybrids in Which Several
Differentiating Characters are Associated.
DIHYBRID CROSSES
75
Interpreting the Data

• The F2 generation contains seeds with novel
  combinations (ie not found in the parentals)
• Round and Green
• Wrinkled and Yellow
• These are called nonparentals
• Their occurrence contradicts the linkage model

76

• If the genes, on the other hand, assort
  independently
• Then the predicted phenotypic ratio in the F2
  generation would be 9331

• Mendels data was very close to segregation
  expectations

77
Second Mendel Law

• Law of Independent assortment
• During gamete formation, the segregation of any
  pair of hereditary determinants is independent of
  the segregation of other pairs

78
8 The Offspring of Hybrids in Which Several
Differentiating Characters are Associated.

• (5th last par) If n represent the number of the
  differentiating characters in the two original
  stocks, 3n gives the number of terms of the
  combination series, 4n the number of individuals
  which belong to the series, and 2n the number of
  unions which remain constant.
• i.e.,
• Looking at crosses from dihybrids (hybrid for two
  traits)
• 32 different combinations (genotypes)
• 42 individuals
• 22 different unions (phenotypes)

79
(end 1st par) Since the various constant forms
are produced in one plant, or even in one flower
of a plant, the conclusion appears logical that
in the ovaries of the hybrids there are formed as
many sorts of egg cells, and in the anthers as
many sorts of pollen cells, as there are possible
constant combination forms, and that these egg
and pollen cells agree in their internal
compositions with those of the separate forms.
9 The Reproductive Cells of the Hybrids
80

• 9 The Reproductive Cells of the Hybrids
• Independent assortment is also revealed by a
  dihybrid test-cross
• TtYy X ttyy (expt 2 4)

• Thus, if the genes assort independently, the
  expected phenotypic ratio among the offspring is
  1111

81
Molecular basis

• Modern geneticists are often interested in the
  relationship between the outcome of traits and
  the molecular expression of genes
• They use the following approach
• Identify an individual with a different copy
  (allele) of the gene variant (mutant)
• Observe how this copy will affect the phenotype
  of the organism

82
Molecular basis

• The defective copies are termed loss-of-function
  alleles
• Unknowingly, Mendel had used several of these
  alleles in his studies on pea plants
• Loss-of-function alleles are commonly inherited
  in a recessive manner

83
Molecular basis
In the wild-type the gene X encodes the enzyme X
that catalyses the reaction
Uncolored pigment precursor
Red pigment
Red eye
In the variant the gene X is inactive, the enzyme
X cannot catalyse the reaction (not produced)
Uncolored pigment precursor
Red pigment
White eye
84
X-linked inheritance
Reciprocal cross
85
X-linked inheritance
86
Summary

• Autosomal Traits
• 32 different combinations (genotypes)
• 42 individuals
• 22 different unions (phenotypes)
• X-Linked Traits
• Diverges from above
• Switch in phenotypes when starting with female
  recessive