1. Genetics/lab
BIOL 3600 DA7
De Santis 3046
Fall 2014
Lecture: M,W,F 4:15 - 5:05 pm
Lab: Parker 219
Monday 6-8:45 pm
Wednesday 6-8:45 pm

2. Review of the syllabus
Instructor
Dr. Paula Faria Waziry
Office: UPP North 3450 suite 103
Phone: 2-2872 (don’t leave message!)
Skype: paula.waziry
Office hours: by appointment
E-mail – waziry@nova.edu
Lab assistant
Nishant Talati
Text
Pierce, Benjamin A 2014. Genetics: A Conceptual Approach,
5th Edition, W.H. Freeman, New York, NY (ISBN number 2013951443)
Website
All course materials will be posted on Blackboard prior to the class period
- PowerPoint presentations
- Lab information
- http://www.slideshare.net/paulawaziry1 (when BB is down...)

3. Review of the syllabus
Class assignments
Unit exams (40% of final grade)
- 2 will be given (20% each)
- Each will consist of three sections – multiple choice, short answer, essay
- Responsible for all material covered in the Powerpoint presentations.
- ~90 minutes to complete
- Make-ups – must have an approved excuse in writing (as per the NSU catalog)
- Must contact me ASAP (before the exam, if possible)
- If don’t have excuse in writing, points will be deducted for make-up
Final exam (20% of final grade) – cumulative
Quizzes – lab and lecture (15% of final grade)
- Approx. 10 minutes each
- Only covers material since the last quiz
- You can drop 2 lowest quizzes grades.
- No make-ups unless you have an excuse in writing.

4. Review of the syllabus
Lab assignments
Lab final (10% of final grade)
- Cumulative – all labs and techniques
- See lab syllabus for more information
Lab reports, lab attendance and participation (15% of final grade)
- You must keep a written account of all experiments during the semester
- Include purpose, methods, results, and discussion/conclusion for
ALL EXPERIMENTS DONE
- Unexcused absences will result in major point deductions

5. Review of the syllabus
Grades
The final average will be calculated as follows:
two unit tests @ 20% each ```40%
Final exam 20%
Quizzes 15%
Lab final 10%
Lab activities 15%
100%
The grading scale: 93% = A,
90-92%=A-,
87-89%=B+,
83-86%=B,
80-82%=B-,
77-79%=C+,
73-76%=C,
70-72%=C-,
60-69%=D,
<60%=F

6. Tips for success
1. Attendance is required at all lectures, labs, and exams
- You are responsible for getting any missed info
2. Ask questions in class and participate in discussions
3. Don’t just read and highlight the handouts. Understand and
practice questions.
4. You will be responsible for the conceptual material
covered in class/ Powerpoints.
5. Be considerate: no cell phones, texting, Internet surfing, facebooking,
dozing off, sleeping, snoring…

7. Chapter 1
Introduction to Genetics
 People have understood the hereditary
nature of traits and have practiced genetics
for thousands of years
 The rise in agriculture began when people
started to apply genetic principles to the
domestication of plants and animals

8.  Pharmaceutical industry:
 Numerous drugs are synthesized by
fungi and bacteria.
 Ex: growth hormone, insulin
 In medicine:
 Many diseases and disorders
have a hereditary component.
 Ex: hemophilia, sickle-cell
anemia, diabetes,
muscular dystrophy,
EMD1: Emerin; Xq28;
Recessive
EMD2: Lamin A/C; 1q21.2;
Dominant
EMD3: SYNE1; 6q25;
Dominant
EMD4: SYNE2; 14q23;
Dominant
Other: Sporadic & Dominant
from A Kornberg MD

9. 2 years-old Kristian
Hutchinson-Gilford Progeria
12 years-old Ashley and
2-weeks old brother Evan

10. Defect in Lamina A processing
Hutchinson-Gilford Progeria
Lamin A/C (a)
Lamin A (c)
DAPI
Control Patient

11. Samuel Dales
mRNA
Ribosomal
subunits
tRNA
snRNPs
Proteins
with NES
hnRNPs
Ribosomal
proteins
Proteins
with NLS
snRNPs

12. TPR
(translocated promoter
region)
The Nuclear Pore Complex
Nup98
Nup98
Nup98

13. Nucleoporin Translocations in
Acute Leukemia
Fusion Transcript
• Nup98-HOXA9
• Nup98-HOXD13
• Nup98-PMX1
• Nup98-DDX10
• Nup98-RAP1GDS1
• Nup98-TOP1
• DEK-Nup214
• SET-Nup214
Translocation
t(7; 11)(p15; p15)
t(2; 11)(q31; p15)
t(1; 11)(q23; p15)
inv(11)(p15; q22)
t(4; 11)(q21; p15)
t(11; 20)(p15; q11)
t(6; 9)(p23; q34)
inv(9)

14. Genetic Diversity and evolution
 Living organisms have an important feature in
common:
all use similar genetic systems
 A complete set of genetic instructions for any
organism is its genome
 All genomes are encoded in nucleic acid:
either DNA or RNA
• Suggestive of a common ancestor

15.  Since all organisms have similar genetic systems, the study of
one organism’s genes reveals principles that apply to other
organisms
STAT 1
P
P
SGTAAT S1 motif
Accessory TF
motifs
TATA
Accessory TF
factors

16. Nucleoporins and Nuclear Traffic Proteins are involved
with Mitotic Spindle Checkpoints and Ageing
Baker DJ, Jeganathan KB, Malureanu L, Perez-Terzic C, Terzic A, van Deursen JM.
J Cell Biol. 2006 Feb 13;172(4):529-40.
 Enabling us to
use animal
models to
study diseases
or natural
processes

17. Influenza A pandemic
- Influenza virus killed as
many as 50 million people in
a single year (1918-1919)
- Extremely virulent
- Fast, nasty, killed all ages
- Up until 2006, had no idea why
it was so virulent
- Had no way to tell if a similar
strain was forming
- In October 2005, scientists recreated the 1918
strain using various genetic techniques
- Obtained samples of the virus
from preserved wax specimen and
from a Eskimo woman who had
died from it
- Able to characterize it and maybe predict /
prevent future outbreaks

18. Microarray study reveals changes in regulation of genes
Upon influenza viral infection
Replication-dependent genes
Geiss G, J.Virol, May 2001,p4321-4331

19. Cells expressing low levels of Rae1
are susceptible to influenza infection

20. Influenza virus targets the mRNA export
machinery and the nuclear pore complex.
Satterly, Tsai, van Deursen, Nussenzveig, Wang, Faria, Levay, Levy, Fontoura.
Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1853-8.

21. Genetics
What is it?
http://www.youtube.com/watch?v=0Onw
OKiMVb8&feature=channel_video_title

22. • Genetics = Study of HEREDITY and VARIATION
- Heredity = Passing down of traits from one generation to another
- Variation = Differences in inherited characteristics among members of a
population

23. Genetics
What is it?
• Genetics has many subfields
1. Transmission genetics – Study of heredity
- How traits are passed down between generations
- Example: My mom has disease, spouse's uncle has
same disease  Will our kids have it?
- Is allele dom/rec, is it on X chr or autosome?
2. Molecular genetics – Structure and function of individual genes
- Includes study of cancer (cancer genetics), genetic engineering
(manipulation of genes), study of chromosome structure (cytogenetics)
3. Population/Evolutionary genetics – Study genetic variation in populations
- Includes conservation genetics

25. History of genetics
• Early genetics was more philosophy than science
- No experimentation
- Many concepts were incorrect
- Pangenesis – traits collected from all over body and
put into sperm/eggs
- Pre-formationism – little person inside of gametes (homunculus)
- Blending inheritance – actual mixing of genetic information

26. “Blending”

27. History of genetics
• Technological and scientific developments changed
genetics in 1800s
- Microscopes invented
– direct observation of gametes
- Darwin and Mendel revolutionize genetics
- Evolutionary and transmission genetics begin
- Chromosomes observed and discovered to carry
genetic information (early 1900s)

28. Chapter 2
Chromosomes and Cellular Reproduction

29. 1. Nucleus vs nucleoid
- Nucleus – Membrane-enclosed organelle inside of eukaryotic cells that holds
the chromosomes
- Nucleoid – Region of a prokaryotic cell cytoplasm in which the chromosome
resides
2. Chromosome
- Single piece of DNA + proteins
- Can be linear (eukaryotes) or circular (prokaryotes)
- Eukaryotes have many, prokaryotes have one
- Divided into many genes

30. The Nucleus in Context
(the central dogma)

31. • Origin of the Nucleus: Most likely, from invagination of cell membrane of
an ancient bacterium. The interior of the nucleus is topologically
equivalent of the cytoplasm.
• The ER is continuous with the nuclear membrane. The intermembrane
space is topologically equivalent to the extracellular space.
Evolution of the Eukaryotic Nucleus

34. Chromosome Territories
Chromosome distribution is not random

35. Chromosome Territories
 Chromosomes maintain their individuality
 they have fixed homes spatially limited volume
 Each chromosome of a specific cell type can be assigned a
preferential position relative to the center of the nucleus
 territories have highly branched and interconnected
channels
Good Review:
Meaburn and Misteli, Nature, Jan 25, 2007, vol445, pp379 - 381

36. Chromosome Structure
• Centromere: attachment point for spindle
microtubules
• Telomeres: tips of a linear chromosome
• Origins of replication: where the DNA synthesis
begins

37. At times a chromosome
Consists of one single chromatid
At other times it consists of 2
(sister) chromatids
The telomeres are the stable
ends of chromosomes
The centromere is a constricted
region of the chromosome where
The kinetochores form and the
Spindle microtubules attach

38. Centromeres can be located at
different sites on a chromosome

39. 3. Gene
- Defined segment of a chromosome that provides the instructions to make a
single product (a protein)
- One chromosome may be subdivided into 1,000 different genes
1 chromosome
insulin ATP
synthase
actin hemoglobin
 Chromosomes are divided into genes, which are composed of DNA
4. Diploid vs. haploid
- Most eukaryotic organisms have 2 copies of each chromosome in each of their
somatic cells
- 2 copies = 2n = DIPLOID
- Gamete cells (e.g. sperm and eggs) contain only 1 copy
- 1 copy = 1n = HAPLOID

40. • Some more genetic terms (and how they relate to one another):
5. Alleles
- Alternate forms of the same gene caused by minor differences in the DNA
sequnce
6. Genotype vs phenotype
- Genotype – The genetic makeup of
an organism (what the genes look like)
- Phenotype – The actual observable
characteristics that we see
- Influenced by the genotype and the
environment
eye color
blue eyes
brown eyes

41. Quick review of Mitosis
http://www.youtube.com/watch?v=AhgRhXl7w_g&feature=fvst

43. Genetic consequences of the cell cycle
• Producing two cells that are genetically identical
to each other and with the cell that gave rise to
them.
• Newly formed cells contain a full complement of
chromosomes.
• Each newly formed cell contains approximately
half (but not necessarily identical) the cytoplasm
and organelle content of the original parental
cell.

44. Quick review of Meiosis
http://www.youtube.com/watch?v=iCL6
d0OwKt8&feature=channel_video_title

45. Room for genetic variation

47. Room for genetic vatiation

49. Genetic Variation is Produced through the
random distribution of chromosomes in meiosis
Genetic Variation is Produced
through crossing over
• Try Animation 2.3
file:///E:/media/ch02/Animations/0203_genetic_va
r_meiosis.html

50. Consequences of Meiosis and Genetic
Variation
• Four cells are produced from each original cell.
• Chromosome number in each new cell is
reduced by half. The new cells are haploid.
• Newly formed cells from meiosis are genetically
different from one another and from the parental
cell.

51. Concept Check
Which of the following events takes place in
meiosis II, but not in meiosis I?
a. crossing over
b. contraction of chromosomes
c. separation of homologous chromosomes
d. separation of chromatids

52. Transmission genetics
Mendel and beyond

53. Chapter 3
Basic Principles of Heredity

54. Transmission genetics
Overview
• Transmission genetics  Study of how genes/traits are
passed down through generations
- Wrong hypotheses in history:
- Pangenesis: Traits absorbed from all over body  sperm/eggs
- Lemarckism: Kids inherit their parents acquired characteristics
- Preformationism: Little people inside of gametes (homunculus)
- Blending inheritance: Traits of parents blend  passed on
• Gregor Mendel – 1850-60s
- Experiments with peas disproved all above
- Found discrete units of inheritance passed down
- Provide instructions for brand new organism
- No blending
- Unique combination of genes provides unique
traits in offspring

55. Transmission genetics
Review of terminology
• Genes = Short segments of chromosomes/DNA that
provide instructions to make a polypeptide
• Alleles – Different forms (variations) of the same gene that result from minor
differences in the DNA sequence
- Example: Gene controlling melanin
• Homozygous vs. heterozygous
Homozygous – Organism has 2 copies of the same allele for a given gene
Heterozygous – Organism has 2 different alleles for a given gene
• Dominant vs. recessive
- In a heterozygous individual, both alleles are expressed
(assuming no imprinting)
- However, one allele often has a greater impact on the final observable trait
- Those alleles that mask the effects of other alleles  DOMINANT
Those alleles that get masked  RECESSIVE

56. Simple Mendelian inheritance
Monohybrid cross
• Simple Mendelian inheritance
- Each trait is controlled by one gene, each gene controls one trait
- Alleles have a clear dominant-recessive relationship
- Individuals have expected phenotype
- If examining more than 1 gene  they are on separate chromosomes
• Monohybrid cross (1 gene)
- Example: Human earlobe shape
- Dominant allele  Unattached (E)
Recessive allele  Attached (e)
- Example mating: Two heterozygotes (Ee x Ee)
- Need to predict offspring genotypes/phenotypes
- Theory of segregation – Two copies of the gene
are segregated and packaged into separate gametes
- 1 gets the "E" and the other the "e"
 Predict a 3:1 ratio of dom:rec phenotypes
- Only a probability – may not see exact ratio
E e
EE Ee
Ee ee
E
e

57. Transmission genetics
Review of terminology
• Genetic shorthand
- Dominant allele  Capital letter
Recessive allele  Lowercase letter
Choose letter wisely!
A = normal melanin production AA (homozygous dominant)
a = no melanin aa (homozygous recessive)
Aa (heterozygous)
• Genotype vs. phenotype
Genotype – Genetic background of a trait (AA, aa, Aa)
Phenotype – Actual observable trait that we see (skin color)
- Multiple genotypes can give rise to the same phenotype (e.g. AA and Aa)
- Not all individuals with a given genotype will have the expected phenotype
• Generation shorthand
- P = Parental generation
- F1 = First filial generation (produced from mating two parents)
- F2 = Second generation (produced from mating 2 F1 offspring)

58. • Why was Mendel so successful?
1) His choice of experimental subject, the pea plant
(Pisum sativum) is easy to cultivate and grow relatively
rapidly
( by 17th century standards);
2) Peas produce many offspring (seeds);
3) Large variety of traits and traits were genetically pure;
4) He focused on characteristics that have 2 forms;
5) He adopted an experimental approach and used math!
6) He kept careful records of his experiments and was
very patient…

59. Simple Mendelian inheritance
Monohybrid and dihybrid crosses
• Simple Mendelian inheritance
- Each trait is controlled by one gene, each gene controls one trait
- Alleles have a clear dominant-recessive relationship
- Individuals have expected phenotype
- If examining more than 1 gene  they are on separate chromosomes
• Monohybrid cross (1 gene)
- Example: Human earlobe shape
- Dominant allele  Unattached (E)
Recessive allele  Attached (e)
- Example mating: Two heterozygotes (Ee x Ee)
- Need to predict offspring genotypes/phenotypes
- Theory of segregation – Two copies of the gene
are segregated and packaged into separate gametes
- 1 gets the "E" and the other the "e"
 Predict a 3:1 ratio of dom:rec phenotypes
- Only a probability – may not see exact ratio
E e
EE Ee
Ee ee
E
e

60. • Dihybrid cross (2 genes)
- Mendel's original experiments:
- Done to determine if inheritance of one gene
affects inheritance of another
- Found that when genes are on different
(nonhomologous) chromosomes,
they move independently during meiosis
and don't affect one another
 Principle of independent assortment
- Example (assuming independent assortment):
- Earlobe shape (gene E) and hairline shape (F – widow's peak, f – straight)
- If mate EeFf x EeFf, what phenotypic ratios in offspring?
FIRST SEPARATE THE GENES…
E e
EE Ee
Ee ee
E
e
F f
FF Ff
Ff ff
F
f
Then do separate Punett squares…

61. E e
EE Ee
Ee ee
E
e
F f
FF Ff
Ff ff
F
f
INDEPENDENT TERMS
E_F_ = double dom. = 3/4 x 3/4 = 9/16
eeF_ = 1 rec, 1 dom = 1/4 x 3/4 = 3/16
E_ff = 1 dom, 1 rec = 3/4 x 1/4 = 3/16
eeff = double rec. = 1/4 x 1/4 = 1/16
9:3:3:1
9+3+3+1=16
Remember that UPPER CASE TRAIT
IS DOMINANT FOR PHENOTYPE!!!
NOW COUNT THE PHENOTYPES!!!

62. Simple Mendelian inheritance
Monohybrid and dihybrid crosses
• Dihybrid cross (2 genes)
- Example problem:
- Imagine you mate a person who has attached earlobes and a smooth hairline
with a person who is heterozygous for both genes. What is the probability of
them having a child with unattached earlobes and a widow's peak hairline?
- Step 1: Convert to letters
- Parent 1 = attached, smooth  eeff
- Parent 2 = EeFf
- ? offspring = E_F_
(2nd letter for each doesn't matter)
e e
Ee Ee
ee ee
E
e
f f
Ff Ff
ff ff
F
f
- Step 2: Do two Punett squares
- Split up the E's from the F's
- Step 3: Do the math
- Multiply the individual probabilities
- E_F_ = 1/2 x 1/2 = 1/4