Class 1 of Genetic Revolution and You - Adult School of Montclair, NJ, Fall 2014

1. Welcome to
The Genetic
Revolution and You
• Please sit only at the tables.
How rapidly advancing genetic
and biological knowledge are
affecting and will affect your
health and well-being and that of
future generations

2. Welcome toThe Genetic
Revolution and You
Adult School of Montclair
Fall 2014
Dr. David Reibstein

3. Created by David Reibstein, Ph.D.,
for the course
The Genetic Revolution and You:
Today and Tomorrow
Fall 2014
Adult School of Montclair
Copyright 2014 David Reibstein

4. “The notion of the infinite variety of detail and
the multiplicity of forms is a pleasing one; in
complexity are the fringes of beauty, and in
variety are generosity and exuberance.”
‐Annie Dillard, American author, b. 1945

5. Aims of This Course
1. To describe and clarify modern genetics, and
describe its basis in molecular knowledge
2. To show how this knowledge has been acquired
3. To discuss some of the ways in which this knowledge
is being used, and might be used in the future, for
understanding:
a) the living world
b) the treatment and reduction of disease
c) the extension of healthy life-spans
4. To discuss the ethical, legal, and social implications of
current and future developments in genetics.

6. Outline of the Course
1.Overview and Objectives
2.The chemical and biological basis of life and
its organization on earth
3.Chemicals of Life: DNA, RNA, and proteins
4.Genes and Genomes: How genes make us
what we are
5.The Human Genome Project (HGP) and what
we have learned from it
6.How the HGP is leading to new approaches to
health care:

7. a. Finding genes that contribute to disease
b. Resilience to mutations
c. Editing Our Genome
d. Aging
7. Cancer: What genetics tells us
8. The Microbiome – the microbes that live
inside you and what they do for you
9. Viral diseases: Influenza, Ebola,
10.A Possible Future:
a) “Designer Children”
b) “Personalized Medicine”

8. Along the way, you and I will discuss the
ethical, legal, and social issues that arise
from these developments.
The format of these discussions will vary
depending on the topic.
Along the way, you and I will discuss the ethical, legal,
and social issues that arise from these developments.

9. I welcome questions that seek
clarification.
• However, I may choose to address the question after
class if I think the answer is complicated, or I judge it
to be not of interest to everyone, or not completely
relevant to the course. (I enjoy talking about
anything with anyone!)

10. Let’s start with 2 questions
1. What is the “Genetic Revolution?”
–Knowledge about the organization of
human genes has opened up wide areas of
research, which will affect:
• Health care
• Reproduction
• Life spans

11. What kinds of knowledge?
• How the structure of DNA contains
instructions for making and regulating an
organism
• How mutations (changes in DNA)
have affected evolution and how
they affect our health.
• Human genetic variation

12. What kinds of knowledge?
• The Human Genome Project - Launched 1990,
completed 2003:
–the complete sequence of human DNA,
which is leading to:
–A fuller understanding of how our genetic
machinery operates.

13. Some important points in the history
of genetics
1856-1865 Gregor Mendel’s experiments with peas show that
inheritance obeys simple rules. His work was largely
ignored
1859 Charles Darwin: On the Origin of Species
1944 DNA is shown to be the genetic material, and to
consist of a string of 4 bases
1953 Structure of DNA shown to be a double helix:
Watson & Crick with data from Rosalind Franklin
1956 DNA shown to be organized into 23 pairs of
chromosomes in humans
1956 Mechanism of duplication of DNA worked out
1977 Fred Sanger and colleagues work out method for
sequencing DNA
2003 Completion of Human Genome Project

14. The Second Question
2. Why does it make sense to say “Every disease
has a genetic component?” What does that
mean, and how can this be true?

15. “All diseases have a genetic
component.”
Eric D. Green, M.D., Ph.D., Director of the National
Human Genome Research Institute (NHGRI) at the
National Institutes of Health (NIH)
What does this mean exactly?
And how can this be true?
Let’s begin with a quote that I used in
the descriptive paragraph on the Adult
School web site.

16. What is a gene?
• A gene is a segment of DNA.
• Genes can have one of two
functions:
–Structural genes: carry
the code for one or more
proteins.
–Regulatory genes:
regulate processes in the
organism.
• A gene is the molecular unit of heredity.

17. What do regulatory genes do?
• Some code for proteins that
regulate body processes.
• Some are sites of recognition for
other molecules that regulate the
production of other proteins.

18. Genes regulating other genes
These controls can be
very complex.
A regulatory gene controls the function of
other genes in the same way as a TV
remote controls a television.
Schematic example

19. An example of a regulator gene
1. Regulator
gene…
2. makes
repressor
protein, …
3. which
regulates
another gene

20. Genetic components of disease:
Diseases can be divided into two categories
1. Monogenic diseases: rare, catastrophic diseases
caused by a single gene variant, such as cystic
fibrosis.
– For 127 such diseases, we presently know of 164
genes harboring 685 known variants.
2. Most common diseases are due to multiple genes.
For example, inflammatory bowel disease,
rheumatoid arthritis, type 1 diabetes, cancer,
Alzheimer’s disease, schizophrenia, and asthma.
– Thousands of variants spanning many hundreds of
genes have now been associated with these
diseases.

21. 54 monogenic diseases can be detected by
Preimplantation Genetic Diagnosis
• Achondroplasia
• Adrenoleukodystrophy
• Alpha thalassaemia
• Alpha-1-antitrypsin deficiency
• Alport syndrome
• Amyotrophic lateral sclerosis
• Beta thalassemia
• Charcot-Marie-Tooth
• Congenital disorder of
glycosylation type 1a
• Crouzon syndrome
• Cystic fibrosis
• Duchenne and Becker muscular
dystrophy
• Dystonia 1, Torsion
• Emery-Dreifuss muscular
dystrophy
• Facioscapulohumeral dystrophy
• Familial adenomatous polyposis
• Familial amyloidotic
polyneuropathy
• Familial dysautonomia
• Fanconi anaemia
• Fragile X
• Glutaric aciduria type 1
• Haemophilia A and B
• Hemophagocytic
lymphohistiocytosis
• Holt-Oram syndrome
• Huntington's disease
• Hyperinsulinemic hypoglycemia
• Hypokalaemic periodic paralysis
• Incontinentia pigmenti
• Lynch syndrome
• Marfan syndrome
• Menkes disease
• Metachromatic leukodystrophy
• Mucopolysaccharidosis type II
(Hunter syndrome)
• Multiple endocrine neoplasia
(MEN2)
• Multiple exostosis
• Myotonic dystrophy
• Neurofibromatosis type I and II
• Non-syndromic Sensorineural
Deafness
• Norrie syndrome
• Osteogenesis imperfecta (brittle
bone disease)
• Polycystic kidney, autosomal
dominant
• Polycystic kidney, autosomal
recessive
• Pompe's syndrome
• Sickle cell anaemia
• Smith-Lemli-Opitz syndrome
• Spastic paraplegia 4
• Spinal and bulbar muscular
atrophy
• Spinal muscular atrophy
• Spinocerebellar ataxia 1, 2 and 3
• Spondylometaphyseal dysplasia
(Schmidt)
• Tay-Sachs disease
• Treacher Collins
• Tuberous sclerosis
• Von Hippel-Lindau syndrome

22. And while we’re on the subject of
genes:
• What is DNA?
• For now, let’s just note that DNA is a molecule
that contains all the information for
constructing and regulating an organism.
– Instructions for making proteins
– Instructions that guide and regulate:
• Our development from conception
• Our growth
• Our functioning

24. The Old Way of Classifying Life
Animals
Plants

25. But it turned out that life is more
complicated than that
Let’s look a little closer

26. Us
First living organism – probably at least 2 – 3.5 billion years ago
Split between animals
and plants happened
more than 1 billion
years ago.

27. Before we go any further, let’s get
acquainted with the relative sizes
of things

28. How small are molecules?
• An 8-ounce glass of water contains
on the order of 1023 H2O molecules.
• That is
100,000,000,000,000,000,000,000
million
million
million
million

29. Flea
Amoeba: 200
micrometers =
0.2 mm
Eukaryotic cell
Large virus
200 nm = 0.2 μm
Cell membrane (L)
Small virus (R)
DNA : 2 nanometers =
2
1000
micrometer
Mitochondria (L)
Bacteria (R)
Skin cell
Larger
Smaller
= 0.2 millimeters (mm)
= 0.008 inches or
8
1000 of an inch
125 hairs placed side by side
take up 1 inch
125 hairs
Decreasing by
factors of 10
Hair thickness
200 micrometers

30. Life is organized into cells
Prokaryotes – cells without
nuclei: 4 billion years ago.
Eukaryotes – cells with
nuclei and other internal
structures: less than 2
billion years ago.

31. Prokaryotes: No internal structures.
They were the first cells that
lived on earth. Arose 4 billion years ago.
Example: bacteria
Eukaryotes: Contain internal structures
bounded by membranes, such as nucleus,
mitochondrion. Less than 2 billion years ago.
Examples: plants, animals, protozoa

32. We are outnumbered
• Eukaryotes are a tiny minority of all living things.
• However, because of their much larger size, their total
collective mass is about equal to that of prokaryotes.
• We’ll learn more about this when we look at the living
things inside you.

33. In complex organisms
(multicellular organisms) cells are
organized together into tissues
Specialized proteins glue cells together

34. The Cells of the Human Body
• Humans have about 200 different types of
cells.
–Within these cells there are about 20
different types of structures called
organelles.
• All of these cell types are derived from a single
fertilized egg cell. All cells have the same
genetic material (genome).

35. How do cells become
different?
• This is one of the
most important
current research
questions.
• Difference between
cells largely depends
on which genes are
turned on or off, and
when.
• What controls this?
This question is at the
heart of modern
genomic studies.

36. What Are the Important Chemical
Components of Life?

37. There are 92 naturally-occurring
elements
• From Hydrogen #1
• To Uranium #92
• An additional 26 elements have been
artificially made in atom-smashers

38. What We are Made Of: Chemical
Composition of the Human Body
Elements in the
Human Body
Percent by
Mass
Oxygen 65%
Carbon 18%
Hydrogen 10%
Nitrogen 3%
Calcium 1.5%
Phosphorus 1.2%
Potassium 0.2%
Sulfur 0.2%
Chlorine 0.2%
Sodium 0.1%
Magnesium 0.05%
Iron, Cobalt,
Copper, Zinc,
Iodine,
Selenium,
Fluorine
Very
small
percentages,
but all
important
“The big 6”
Only a relatively
small number of
elements make up
organisms.

39. Atoms combine to form molecules
• The water molecule: 2 atoms of hydrogen
(H) and 1 of oxygen (O), = H2O
• Molecules are held together by bonds,
which are formed by the sharing of
electrons.
• The molecules that compose living
organisms are very large, containing
thousands to tens of thousands of atoms.

40. The Important Chemical Components
of Life
• Carbohydrates – sugars, starch,
etc.
• Fats and oils
• Vitamins and minerals
Proteins
RNA
DNA

41. Proteins
• Proteins are the workhorses of the cell.
• Proteins are large molecules – thousands of
atoms.
• Sizes are in the range of about 1 – 5.5 nm
(nanometers, billionths of meters).
• They are made by stringing
together smaller molecules called
amino acids. Amino acids are
designated by 3-
letter
abbreviations.

42. PROTEINS
• A protein is a chain of amino acids linked in
a definite sequence by chemical bonds.
• There are 20 amino acids commonly found
in all organisms, plus one rare one.
• Each protein has a unique number and
sequence of amino acids.
• This sequence is, in turn, determined by
DNA.

43. All the amino acids have a common
structure
R
R stands for one of the 20 different
chemical groups that make each amino
acid unique.
amino
group
carboxyl
group
C = carbon. N =
nitrogen. O =
oxygen. H =
hydrogen

44. The 21 amino acids
Essential – must be obtained in
diet because they cannot be
created from other compounds
by the human body
Nonessential – can be made in the
human body from other substances
in the diet
Histidine Alanine
Isoleucine Arginine*
Leucine Asparagine
Lysine Aspartic acid
Methionine Cysteine*
Phenylalanine Glutamic acid
Threonine Glutamine*
Tryptophan Glycine
Valine Proline*
Selenocysteine* (very rare)
Serine*
Tyrosine*
* May be essential for certain ages or
medical conditions

45. Amino acids have two ends that can
join with other amino acids
These two
groups can
bond together
This car is like an amino acid that can couple at both ends.
Just like railroad cars have two ends
that can join with other cars.

46. Proteins are involved in every function
of a cell
• Proteins vary greatly in size.
• They range from about 100 amino acids to more than
1000 amino acids long.
• Their functions include:
– Digestion
– Energy production
– Transporting nutrients
– Antibodies
– Channels, Pumps and Receptors
– Photosynthesis
– Enzymes for making and
recycling the molecules of life

47. After a protein is made, it folds into a unique
3-dimensional shape , dictated by its sequence of
amino acids.
Linear protein chain Folded-up protein in 3-D
The 3-D structures have 3
types of structural elements.

48. A 3-D View of a Protein – Human
Serum Albumin – which is composed
entirely of helix
A 3-D animated view of this
same protein
Static 2-D view
• Albumin occurs in the blood.
• It has many functions, including carrying fats.

49. Let’s go to PDB and look at two more
proteins:
• One spherical (an enzyme), which contains
all 3 types of structure
• The other is myosin, one of the proteins of
muscle, which is an elongated (fibrous)
protein. It is entirely made of helix.
PFK, a human enzyme that
metabolizes sugar
Human myosin, one of the
muscle proteins

51. Proteins are related in families
• Just as families of organisms derive from a
common ancestor, families of proteins result
from divergent evolution of a single gene.
• Proteins in a family typically have similar three-
dimensional structures, functions, and
sequences.
• Computer programs are used to match proteins
with others, sort them into families by
sequences, and determine evolutionary histories.

52. The Cas-7 family of proteins
• These proteins help bacteria fight off virus
attakcs – more later

53. Family tree
for G
protein-
coupled
receptors
An important
family of signal-
receiving proteins.
At least 800 exist
in humans.

55. • An example of a family
of proteins:
the cyclophilins, which
help organize other
proteins.
• Found in all cells of all
organisms studied, in
both prokaryotes and
eukaryotes.
• Humans have a total of
16 cyclophilin proteins.
• Note similar 3-D shapes

56. An Important Biological Principle
Structure
Determines
Function
What a protein is capable of doing is entirely
determined by its 3-dimensional structure and
which amino acids occupy each position.