FUNDAMENTALS GENETICS

SYLLABUS SPRING 2008

Additiveeffects Additiveeffects
Instructor:
Dr. Barbara Sears
Director, Genetics Graduate Program
Professor, Department of Plant Biology
Michigan State University
East Lansing, Michigan 48824
Email: sears@msu.edu

CAN THO UNIVERSITY
Biotechnology R&D Institute
March 24 ~ April 01 2008
ZOL/PLB 341 - FUNDAMENTALS OF GENETICS
SYLLABUS - FALL 2006
Lectures: 11:30-12:20 MWF in Rm 1281 Anthony Hall
Recitations: all take place on Tuesday (see schedule below)
Instructor: Phone: Office Location: Office Hours:
Dr. Barbara Sears (BBS) 355-0132 Rm 37 Plant Biology Bldg Mon 2-3:45 pm
Required Purchases:
Genetics: A Conceptual Approach, 2 edition (2005) by Benjamin Pierce, packaged
nd
together with a CD ($118.65 new)
i-Instruction individual response pad (~$30)

Prerequisite: BS111 Cells and Molecules
Web Site: Start at the opening page for the Universitys ANGEL web system for courses,
which can be found at: http://www.angel.msu.edu. You will need to enter your MSU userID
(without the @msu.edu) and your password. All of your courses that use ANGEL should be
listed here. You should have two listings for ZOL/PLB 341: one for the lecture part of the
class, and one for your recitation. Consult the web site for announcements, and for questions
about course policies, the class schedule, help sessions, office hours, etc. The information
will be updated frequently.
Genetics Recitations
Recitation Teaching Recitation Recitation
Section: Assistant Time (Tues) Location
001: Philip Ludwig 9:10 - 10:00 am 305 Bessey Hall
002: Mike Wiegand 9:10 -10:00 am 140 Nat Sci
003: Meghan Drummond/Nissa Reichenbach 10:20 -11:10 am c313 WellsHall
004: Brad Cavinder 11:30 am -12:20 c315 Wells Hall
005: Weifeng Mao 12:40 - 1:30 pm c311 Wells Hall
006: Sankalpi Warnasooriya 3:00 - 3:50 pm 204 Nat Sci
007: Meghan Drummond /Nissa Reichenbach 9:10 -10:00 am c214 Wells Hall
008: Sankalpi Warnasooriya 1:50 - 2:40 pm 106 Bessey Hall
009: Weifeng Mao 1:50 - 2:40 pm 1234 Eng
010: Philip Ludwig 10:20 -11:10 am 113 Bessey Hall
011: Brad Cavinder 1:50 -2:40 pm 311 Bessey Hall
One of the four credits for ZOL/PLB 341 is allocated for the weekly recitation period,
and therefore, your attendance is expected. The recitations are run by the teaching
assistants for this course, and together with the help rooms, they provide an opportunity to
learn analytical approaches to solving questions, and provide individual help, which is
difficult to achieve in a large lecture class. The teaching assistants will also be presenting
some new material in the recitation period, and they will provide practice problems that are
derived from old exams. The TAs will have 25 discretionary points to assign to each
student, based on attendance and participation.
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THE ORGANIZATION OF ZOL/PLB 341
1. OBJECTIVES. This course is intended as a general introduction to genetics. Students
will receive an introductory survey of the entire discipline, and every chapter of the textbook
will be covered. It is not designed to train professional geneticists, but the course will
provide a good foundation for those who might be so inclined. Basic principles and the
logic and experimental methods of genetics will be emphasized.
2. EXAMS.
Format: There will be three (3) one-hour mid-term exams which will all take place in 1281
Anthony Hall at the regularly scheduled class time on: Friday, September 22, Friday,
October 13, and Friday, November 10. The final exam is two hours in length and is
scheduled for Wednesday, December 13, at 10:00 am. Each exam will be "closed-book"
and will consist of questions derived from material from the lectures, the text and the
homework problems. The exam questions will ask for short answers and problem-solving;
there will be few multiple choice questions. Although students are encouraged to work
together in study groups, the collaborative effort should cease when exams are taken.
Grading and regrading: The exam questions and answers will be discussed at the
recitations following the exams and the answers will be posted outside Dr. Sears office
after each exam. Students are given one week after the exams are returned to submit
requests for regrading. A cover sheet must be attached to the exam, in which an
explanation is provided for why the question was incorrectly graded. Except for the
instances when the discrepancy is due to a mathematical error in calculating the total
points, all exams submitted for regrading will be regraded in entirety, and it is possible to
lose points on a regrade request.
Excused absences: MSU policy will be followed with regard to health or medical problems
that cause students to miss an exam: If there are any anticipated problems with attending
an exam, students are required to inform one of the instructors ahead of time, except in the
case of an emergency, and to inform their TA of any anticipated problems in attending the
recitation sections. Approved excuses for missing an exam are: medical (requires doctor's
note specifying that the severity of illness requires absence from exam), and death in
immediate family (requires copy of obituary announcement from newspaper). No make-up
exams are given; rather, in the case of an authorized absence, the remaining grades in the
course will be averaged to determine a student's final grade.
3. HOMEWORK. Homework questions will be made available each week through the
LON-CAPA system. They must be completed by 10 pm every Thursday. The questions
will cover the material from the preceding 7 days. Please get in a habit of going to the
LON-CAPA web site at a standard time every week, as extensions will not be given if you
forget. Each homework assignment will be worth 10 points, and in most cases will be
composed of five questions.
You can get to the LON-CAPA web site through a link at our ANGEL course web site, or
you can log on directly: http://msu.loncapa.org/ . Either way, you will have to enter your
UserID and password. The LON-CAPA problems have variables that change for each
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student, so the right answer for you may be the wrong answer for someone else. You
will have three chances to provide a correct answer for each problem. You may post
messages on the discussion board for each problem if you find that you need help with a
particularly challenging topic... The discussion boards will be viewed by one of the TAs
or the instructor several times every day.
4. OPTIONAL EXTRA-CREDIT CLICKER QUESTIONS. During each lecture, we will
have 2-5 clicker questions. If you wish to have an opportunity to earn extra credit (1 pt
per class period) you will need the radio-frequency clicker unit produced by i-Instruction.
To receive credit for participating on any given day, answers must be submitted for at
least half of the questions. Since these are extra-credit points based on attendance, the
points cannot be earned by students who are not present, even if they have an excused
absence. It is considered cheating to key in a response using someone elses clicker. It
is your own responsibility to have a functional clicker. The instructors will NOT supply
replacement batteries nor assume any responsibility if students lose or forget their
clickers. After the initial registration grace period, we will assume that the data collection
and participation points are being tracked correctly.
5. POLICY TOWARDS ACADEMIC DISHONESTY. Official MSU policy will be followed
with regard to cheating: a failing grade will be assigned to any student caught cheating
on an exam or any other exercise. Use of a web site to post homework questions and
answers is considered to be cheating, although students are encouraged to help each
other solve problems by posting messages at the LON-CAPA discussion boards.
Although students are encouraged to work together and/or seek help, its because
working together and talking about the interpretation of a question helps build
understanding. That is NOT the case when people copy answers that are posted at a
web site.
6. GRADING. A total of 675 points can be earned in the course, as shown below.
Point Distribution Total Points Earned
614 - 675
(Percent) Grade
First mid-term exam: 100 pts 91-100% 4.0
Second mid-term exam: 100 pts 83-90% 3.5 560 - 613.5
Third mid-term exam: 100 pts 76-82% 3.0 513 - 559.5
Homework: 68-75% 2.5 150 pts 459 - 512.5
Final exam: 200 pts 60-67% 2.0 405 - 458.5
TA discretionary
points
25 pts 50-59% 1.5 337.5 - 404.5
675 pts 40-49% 1.0 Total: 270 - 337
~34 pts 0-39% 0 Potential clicker points: 0 - 269.5
If the instructor concludes that an examination was exceptionally difficult, she reserves
the right to establish a curve by adding points to every exam score. For students who
perform significantly better (an improvement of 1.0 or better) on the final exam than their
cumulative course grade, the final exam grade will be averaged with the cumulative
grade to determine the final course grade.
7. INDIVIDUAL HELP.
Special Assistance. If you have a handicap requiring special assistance, please
seethe instructor so that arrangements can be made to accommodate your needs. If
you fall behind, or find that you need extra help with genetics, graduate students in the
Genetics Program are available to provide tutoring (standard rate: $8-10/hour).
Help room. Two help rooms run by the teaching assistants, will be available
Wednesdays 3-7:00 pm in Plant Biology Room 168-north half. During the week of
each midterm exam, Dr. Sears will provide an evening help session on Wednesday, and
the TA help room will be rescheduled for Thursday evening.
8. CLASS MANAGEMENT TEAM. A class council will be assembled to provide feed-
back to the instructor. At the first recitation period (Aug. 29th), each recitation section
will be asked to select one student representative. The student representatives will
meet once every two weeks (on Tuesday at 5:15 pm) with the instructor to channel
feed-back and suggestions from the class. At any time, general suggestions or
concerns from students can be provided to the instructor either directly, through the
TAs, or through the student representatives.

9. HONORS OPTION: OPENING THE GENETIC TOOL KIT. Every Tuesday evening,
from 6:15-7:15 pm in Rm. 1425 BPS, a 60-minute session will be devoted to a providing
substantial depth on an important topic in genetics. The honors option will be offered by
Adam Nelson, a senior graduate student in the Genetics Program. Current genetics
research will be featured, particularly its applications to society, agriculture, medicine,
and our daily lives. Web-based resources will be included. The weekly topics can be
found at the ANGEL web site, in the special syllabus in the Honors Option Folder.
Completion of the honors option requires:
(1) Attendance of at least 75% of the sessions (attendance records will be kept)
(2) several short written reports based on the reading assignments
FUNDAMENTALS GENETICS
SYLLABUS - Spring 2008
Course Site: Biotechnology Research Institute, Cantho University, Cantho, Vietnam
Instructor:
Dr. Barbara Sears E-mail: sears@msu.edu
Director, Genetics Graduate Program
Professor, Department of Plant Biology
Michigan State University
East Lansing, Michigan 48824
1. OBJECTIVES.
This course is intended as a general introduction to genetics. Basic principles will be
covered, with emphasis on the insight into biological processes that can be obtained through
the logic and strategies of genetics.
2. FORMAT.
There will be four one-hour lectures each day for five days: two in the morning, and two in
the afternoon. The lectures of days 2-5 will be preceded by a discussion of the previous
days homework assignment.
3. ASSIGNMENTS.
Homework questions will be assigned each day to challenge students to integrate the major
topics that were covered in the four lectures. The assignment will require the application and
integration of concepts.
4. CLICKER QUESTIONS.
Twenty-five remote response pads (clickers) are being provided to the class. During each
lecture, the class will be challenged by 2-5 multiple-choice clicker questions, and each
person who has a clicker is expected to register an answer in the time allowed. These
questions will help assess student background and comprehension of the topics that are
covered during the lecture. After the initial registration, the software will track the
participation and accuracy of student responses.
5. REFERENCE MATERIAL
Lectures will use examples and figures primarily from Genetics: A Conceptual Approach,
2 edition (2005) by Benjamin Pierce (Freeman Press). The course material is organized
nd
however, along the lines of iGenetics by Peter Russell (Wadsworth Press). Because this is
an introductory course, almost any genetics text book from the last ten years would serve as
a suitable reference.
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Fundamental Genetics Dr. Barbara B. Sears
Lecture 1: The central dogma of genetics; DNA structure & replication
Vocabulary:
nitrogenous base purine deoxyribose guanine thymine uracil
hydrogen bonds pyrimidine ribose cytosine adenine antiparallel
phosphodiester bonds replication nucleotide template dNTPs leading strand
Okazaki fragment ligase proofreading primer fidelity lagging strand
discontinuous & continuous replication telomere telomerase complementary
I. The Central Dogma
II. Structure of DNA
A. DNA contains four nitrogenous bases.
B. The amount of A = T and G = C in dsDNA (Erwin Chargaff)
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C. The nitrogenous bases are components of nucleotides.
D. The nucleotides are arranged into a double helix through a sugar-phospate backbone.
Important features:
sugar-phosphate backbone
H-bonds between bases
antiparallel, complementary strands
5' > 3'
3' > 5'
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III. DNA replication
A. Synthesis of the DNA helix is semi-conservative.
B. DNA is synthesized in a 5'>3' direction
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C. At the replication fork, bidirectional replication occurs.
Lagging strand
Okazaki fragments
Leading strand
3. Essential components of synthesis:
DNA polymerase
Primase
dNTPs
Okazaki fragments
Proof-reading is performed by the 3'>5' exonuclease
subunit of the DNA polymerase
4. RNA primers must be removed and
gaps sealed by ligase
5. Other accessory proteins are required to make the DNA accessible:
Initiator proteins unwind the DNA at the origin.
Gyrase, helicase, single-stranded DNA binding protein
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D. Replication in Eukaryotes
1. Features of eukaryotic cells require differences in the process of DNA replication
2. Eukaryotic origin of replication = Autonomously Replicating Sequence (ARS)
3. The telomere problem: DNA synthesis at chromosome ends
Why can't DNA polymerase
replace the RNA primer?
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How telomerase replicates (and extends) the
chromosome ends:
Repetitive DNA found at the telomeres is an
essential feature for their replication by the
telomerase enzyme.
Examples of repeats:
5'-[CCCCAA]-3' - in Tetrahymena
3'-[GGGGTT]-5'
5'-[CCCTA]-3' - in Physarum
3'-[GGGAT]-5'
5'-[CCCTAAA]-3' - in humans, plants,
3'-[GGGATTT]-5' nematodes
..
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Fundamental Genetics Dr. Barbara B. Sears
Lecture 2: RNA Synthesis and Processing
Vocabulary:
RNA polymerase downstream promoter enhancer
transcription factors upstream TATA-box silencer
splicing intron intergenic spacer pre-mRNA spliceosome
editing exon endonuclease guide RNA

I. Chemical Structure of Ribonucleic Acid (RNA)
A. Similarities between RNA and DNA
B. Differences between RNA and DNA
II. Overview of transcription (RNA synthesis)
A. Transcription requires:
1. DNA template
2. Ribonucleotides
3. Transcription apparatus
2
B. RNA synthesis
1. In most cases, only one of the two DNA strands serves as a transcription template
Different genes may be transcribed from different strands
2. The newly synthesized RNA is complementary and anti-parallel to one of the DNA strands
3. Transcription proceeds 5'>3', with new nucleotides added to the 3'-OH end of the new RNA
III. Transcription in bacteria
A. Transcriptional units have three parts:
1. Promoter
2. RNA coding region
3. Terminator
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B. Initiation of transcription
1. RNA polymerase plus sigma factor(s)
2. The sigma factor enables the RNA polymerase to recognize and bind the promoter
Bacterial promoters have two consensus sequences at -10 and -35
3. The frequency of transcription is regulated by the affinity of the RNA polymerase for the
promoters.
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IV. Transcription in Eukarya
A. Multiple forms of RNA polymerase
B. Eukaryotic promoters are more complex than bacterial promoters
C. Accessory proteins recognize and bind the promoter BEFORE RNA polymerase
Transcription factors
D. Control sequences that are far from the gene can influence transcription
enhancers and silencers can act from a distance
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V. Some RNAs are processed in both bacteria and eukarya
A. rRNAs and tRNAs have modified bases and are processed from a larger transcript
chemical modification: usually methylation
intergenic spacers removed
The base sequence shown is for tRNA
Ala
Features:
anticodon arm
acceptor arm
pseudouracil arm
dihydrouridine arm (DHU)
3'-CCA
B. Removal of introns (intervening sequences)
Introns
Exons
Splicing
spliceosomes
Self-splicing
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VI. Distinctive processing steps occur in mRNA of eukarya
A. 5' cap
7-methyl guanosine added to 5' end
B. In eukaryotes: addition of 3' Poly(A) tail

Function of Poly(A) tail
1
Fundamental Genetics Dr. Barbara B. Sears
The Genetic Code and Translation
Vocabulary:
amino acid polypeptide sense wobble
peptide reading frame nonsense
I. Overview of protein chemistry and structure
A. Amino acids are the building blocks
Basic structure: Classes:
Nonpolar, aliphatic R groups
polar, uncharged R groups
Aromatic R groups
Positively charged R groups
Negatively charged R groups
B. Primary structure: amino acid chain
Peptide bonds
C. Higher order structure
2
II. Overview of translation
A. mRNA is translated into a polypeptide chain by
ribosomes
B. Amino acids are brought to the ribosome by tRNAs
C. Each tRNA has an anticodon that recognizes a
codon of the mRNA
D. The amino acids specified by individual codons are collectively referred to as the genetic code
3
III. Characteristics of the genetic code
A. Triplet code
B. Non-overlapping
C. Degenerate
D. Wobble
E. Stop and start signals
F. Almost universal
4
IV. The process of translation
Translation has three major steps:
Initiation, elongation, termination
A. Translation initiation requires:
mRNA with ribosome binding site
Eukarya: 5' cap
Bacteria: Shine-Dalgarno sequence
AUG codon
Initiator tRNA
Eukarya: methionine tRNA
Bacteria: formyl-methionine tRNA
IF1-3
GTP
Two ribosomal subunits

5
B. Elongation phase of translation
Elongation Factors
C. Termination of translation
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D. In both bacteria and eukarya, polyribosomes are found
E. In bacteria and archae, transcription and translation are coupled
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Fundamental Genetics Dr. Barbara B. Sears
Lecture 4: Mutations and Transposable Elements
Vocabulary:
base substitution missense silent mutation reversion
transition nonsense neutral mutation spontaneous mutation
transversion frameshift suppressor replication slippage
I. Mutations and their impact on phenotype
A. Somatic versus germ-line mutations
B. An overview of types of point mutation
1) Impact of a single base change on reading frame:
Missense mutation
Nonsense mutation
Silent mutation
Neutral mutation
2) Insertions and deletions result in frameshift mutations
C. Mutations that occur during Replication
1. Base substitution:
a) Many spontaneous base mutations are caused by wobble
pairing between the bases.
b) What usually happens when the wrong base is inserted
during replication?
- distortion of the helix
2
c) 9/10 replication errors are corrected by the proof-reading function of the DNA Polymerase
Many other mutations are corrected by the enzymes of the Mismatch Repair System.
D) What happens if the mutation is not repaired before the next round of replication?
...it will escape repair.
2. Deletion & insertion mutations - high rate of mutation at sites of short direct repeats
Mutation process: replication slippage
Steps in Replication Slippage:

1. Replication complex pauses or stalls
2. Stand of DNA slips out of position
3. Slipped DNA mis-pairs with repeats on
complementary strand
4. Replication continues
not corrected by proofreading because
the resulting DNA duplex is still properly paired.
The resulting indels are significant for:
forensics and genetic disease
3
D. Reversion mutations and suppressors
Restoration of a wild-type phenotype may occur by:
true reversion = restores the wild-type amino acid sequence and phenotype
suppressor = second site mutation that totally or partially restores a function due to a
mutation primary mutation.
1. Suppression by protein : protein interaction
Intergenic suppression:
Intragenic suppression:
Example 1:
Example 2: 1 letter deletion
THE FAT CAT ATE THE BIG RAT --------------> THE FAT ATA TET HEB IGR AT...
1 letter addition: THE FAT ATA TET tHE BIG RAT...
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2. Suppressor tRNA allows a nonsense codon to be translated.
mutation in the anticodon segment of a tRNA gene, such that one of the stop codons is
translated as an amino acid.
Example:
Thought Question:
Will the presence of a suppressor tRNA that decodes a stop codon have other consequences for the cell?
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II. Repair of DNA damage: multiple ways to repair any lesion
Direct reversal of mutational lesions
Removal and replacement of bases
Example: pyrimidine dimers caused by absorption of UV-irradiation
A. Direct reversal of pyrimidine dimers is through Photoreactivation Repair
light (blue range of spectrum)
UV-damaged cells -------------------------------> photoreactivating enzyme (photolyase)
Figure from
Russells Fundamentals of Genetics
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B. Removal and replacement of bases through:
1. nucleotide excision repair system

2. Error-prone Repair (also called SOS-repair): a last resort when the damage is extensive
Overview:
1. When much DNA damage, a new bypass DNA polymerase is synthesized that enables
DNA synthesis through unreadable blocks (bypass replication).
2. Random nucleotides inserted, resulting in many mutations ( error-prone repair).
...many mutations better than gaps in DNA helix
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Fundamental Genetics Dr. Barbara B. Sears
Lecture 5: Transposable Elements
Vocabulary:
transposons endonuclease IS-elements
transposase autonomous transposition composite transposons
transposable element nonautonomous transposition non-composite transposons
retrotransposon footprint Mu element
Ds, Ac, and P-elements
A. General characteristics of transposable elements
1) Traits:
mobility
proliferation
cause mutation
2) Their insertion creates a short, flanking, direct duplication of host DNA
Staggered endonuclease cut:
- Little or no target site specificity
- Each transposon duplicates the same number of bases each time it inserts.
- The duplications are usually 4-12 bp, and copies can be found on either side of the transposon.
2
B. DNA transposons
1) Terminal inverted repeats are essential for transposition.

2) Transposase enzyme encoded by the transposable element.

Autonomous elements: encode a transposase gene; capable of independent movement.
Non-autonomous elements: do NOT encode a functional transposase; require the
transposase to be provided in trans.
3) Most DNA transposons move by nonreplicative transposition:
Start with: After transposition:
Gene A Gene B Gene A Gene B
----==#######===---- ----===========----- ----=====----- ----=======#######===-----
transposable
element
BUT, usually footprints are left behind
4) Some DNA transposons move by replicative transposition:
After transposition:
Gene A Gene B
----==#######===----- ----=======#######===-----
3
Even non-replicative transposable elements can increase in abundance:

5) Transposable elements cause mutations in several different ways.
a) Insertional mutagenesis
b) Chromosome breaks
c) Rearrangements
4
6. Transposable Elements in Bacteria
a) IS (insertion sequence) elements
1) Each type of IS-element:
- different inverted repeat sequences
- specific transposase
Nomenclature (IS1, IS2, IS3...)
2) Ubiquitous

b) Composite transposons are created when two IS-elements mobilize the entire segment of DNA
between them.
Nomenclature (Tn1, Tn2...)
7. Transposons were first discovered in eukaryotes:
a) Transposons were first observed in maize by Barbara McClintock
The first
phenotypes purple colorless colorless purple sectors
observed by (wild-type) (mutant) (due to transposon) (due to excision)
McClintock:
C-locus: c c C C
t
+ - t
-----=======-----
at the DNA
level: -----=======----- -----==X====----- -----=======----- -----=======-----
c
+
5
The size of the sector indicates whether the transposon excised early or late.
figure modified from Fairbanks & Anderson:
Genetics; the Continuity of Life
Autonomous elements: e.g., McClintocks
Activator element (Ac)
Non-autonomous elements: e.g.,
McClintocks Dissociator elements (Ds) have
deletions in the transposase gene
Note: The transposase encoded by Ac is
specific for the Ac-Ds transposons.
Other transposons in maize are not
affected by the Ac-transposase.
b) Drosophila transposons have helped us understand copy number control
(1) P-elements
hybrid dysgenesis only when
P-elements donated by the
paternal parent
Today, all D. melanogaster collected from the wild have P-elements: steady state level of ~50.
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C. Retrotransposons - only in eukaryotes
1. Movement through an RNA intermediate
(DNA --> RNA ----------------------> DNA that inserts elsewhere).
Reverse
Transcriptase
2. One class of retrotransposons appears to be derived from retroviruses.
(single-stranded RNA viruses that can integrate into genomes)
a) long terminal repeats (LTRs) in direct orientation
b) Some shared genes: e.g., reverse transcriptase gene
c) Examples
Ty element of yeast
Copia element of Drosophila
Maize: about 75% of its genome
Some LINES in humans
3. Members of another major class of retrotransposons do not resemble retroviruses, but
DO transpose through an RNA intermediate.
... SINES
e.g., Alu element of humans
1
Fundamentals Genetics Barbara B. Sears
Lecture 6 - Biosynthetic Pathways, Auxotrophy, Complementation
Vocabulary:
auxotrophy phenotype minimal medium genetic block
prototrophy genotype complete medium
I. Biosynthetic Pathways
A. In the 1940s, working with Neurospora crassa, George Beadle and Edward Tatum applied X-rays
to enable them to isolate a range of auxotrophic mutations.
Mutations represented different disrupted biosynthetic pathways
Beadle & Tatum proposed "one gene -- one enzyme" hypothesis
Although we now know that this is an oversimplification, it is a good starting point for our
consideration of biosynthetic pathways:
....Each gene encodes a polypeptide
....Some polypeptides are enzymes
....Some gene mutations will result in defective enzymes

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B. Genetic blocks in biosynthetic pathways
1. Molecules are synthesized as a series of enzyme-catalyzed steps
enzyme 1 enzyme 2 enzyme 3 enzyme 4
Pathway substrate A B C end product
2. The enzymes are encoded by genes.
3. Site of genetic block can be deduced by intermediates that accumulate.
4. Addition of a compound that is synthesized before the block will not result in the production
of the end product.
5. If any compound that comes after the genetic block is provided to the mutant, this will allow
the mutant to synthesize the end product (because it has all the other necessary enzymes).
Mutation:
Intermediate that
may accumulate:
Able to survive if provided with:
Intermediate A Intermediate B Intermediate C
End
Product
Enzyme 1
Enzyme 2
Enzyme 3
Enzyme 4
C. Nutritional requirements can result from genetic blocks in biosynthetic pathways.
auxotrophy
replica-plating:
prototrophy

3
Example Problem: Using the arginine biosynthetic pathway shown below, and the information
about nutritional requirements shown in the table below, determine which enzymes are likely to
be defective in the four arginine auxotrophs.
Strain
Growth Response on Minimal Media plus:
Defective Enzyme
Nothing Ornithine Citrulline
Arginino-
succinate Arginine
wild-type + + + + +
argE - + + + +
argF - - + + +
argG - - - + +
argH - - - - +
The phenotype (observed or measurable characteristic) of the argE-H mutants is auxotrophy for
arginine. However, further testing of their growth properties revealed phenotypic differences and
indicated that their genotype (genetic constitution) differs.
On the replica plates below, the growth phenotypes of several mutants can be observed. As
appropriate, match up mutants 1-7 with the argE-H mutations in the previous table.
o 3
o 2
o 1 o 4
o 5
o 6 o7
o 4

o 2
o 4
o 2
o 4
o 5
o 3
o 2
o 4
o 5
o7
o 3
o 2
o 4
o 5
o 6 o7
Complete Minimal

Minimal +
Ornithine
Minimal +
Citrulline
Minimal +
Arginino-
succinate
Minimal +
Arginine
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D. Even when the phenotype is exactly the same, the mutations may not have occurred in the same
gene.
1. A complementation test allows one to recognize whether recessive mutations with the
same phenotype are due to mutations in the same gene. To perform a complementation test,
cells must be created that are heterozygous for both mutations, as illustrated below:
Example for Neurospora arginine auxotrophy:
Complementation Test:
If arg1 and arg2 are
mutations in different loci:
Phenotype If arg3 and arg4 are
mutations in the same locus:
Phenotype
arg1
-------x-----------------------------
-
-----------------------------x-------
-
arg2
arg3
--------x------------------------------
-
----------------x----------------------
-
arg4
2. Complementation and biosynthetic pathways:
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E. Many genetic diseases of humans are due to mutations that disrupt metabolic pathways
1. Biosynthetic pathways
Example:
Lesch-Nyhan syndrome - an X-linked fatal trait due to deficiency in hypoxanthine guanine
phosphoribosyl transferase (HGPRT), an enzyme required for the phosphorylation of the purines,
hypoxanthine and guanine.
2. Break-down pathways can also be important
Example: Phenylalanine - tryosine metabolism
Human genetic diseases in this pathway:
1) Alkaptonuria - black urine disease studied by Archibald Garrod
2) Phenylketonuria (PKU) - 1/10,000 births; if untreated by dietary adjustment, mental
retardation, slow growth, and early death will occur. A side effect from the inability to make
tyrosine is that little melanin is synthesized (fair hair, blue eyes).
3) Albinism - defect in melanin synthesis; sensitivity to UV-light
F. Some aspects are now known to be more complex than visualized by Beadle and Tatum's One
Gene--One Enzyme Hypothesis.
1. Gene - enzyme relationship
2. One-to-one relationship
1
Fundamental Genetics Barbara B. Sears
Lecture 7: Bacterial genetics: DNA transfer
Vocabulary:
plasmid F-factor R-plasmid conjugation pilus
episome F , F , F biosynthetic pathway exconjugants
+ -
colony origin transformation transduction
I. Genetic markers in bacteria:
A. Bacterial genome:
chromosome
plasmid
Escherichia coli as a model bacterium
II. Movement of genes between bacteria may occur by: conjugation
transformation
transduction
A. Conjugation - unidirectional transfer of DNA through direct
cellular contacts between donor and recipient bacteria.
The F-plasmid provides a well-known example:

1. The F-plasmid contains genes that encode the pili, and it has
an origin of transfer
2. Both of the original strands are replicated, so that both
exconjugants contain the plasmid.
3. If the entire F-plasmid is transferred, the F recipient becomes
-
an F cell.
+
2
4. Integrated plasmid (episome) can also mediate conjugation:
Overview: Hfr strains (high frequency recombination of chromosomal markers).
...Recombinational replacement of chromosomal alleles
Usually, the recipient cells do NOT become Hfr strains.
2. An Hfr cell can become an F OR F cell if the plasmid excises.

When F cells conjugate, the recipient can be
come a merodiploid.
3
3. The existence of Hfr strains enables genetic mapping of bacterial chromosomes.
Earliest transfer: markers
adjacent to the F-integration
site
4
B. Transformation
1. How and why do bacteria take up DNA?
a) naturally competent
b) chemical or electrical shock
2. For recombinant DNA procedures that involve cloning segments
of DNA, small vectors with discrete insertion sites are used, and
the plasmid constructs are transformed into E. coli for
maintenance, storage, and expression.
3. For genes on the bacterial chromosome, transformation requires:
uptake and recombinational replacement
5
4. Linkage of genes in the DNA "donor" can be studied by co-transformation.
C. Transduction (transfer of bacterial genetic information by bacteriophage intermediaries)
1. Overview of bacteriophage lytic and lysogenic life cycles:
6
2. Tolerance of lysogenic phage may have a selective advantage.
A. Protection against superinfection
B. Improved pathogenicity...
e.g., toxin genes encoded by lysogenic bacterophage
2. Generalized transduction can result if bacterial DNA instead of phage DNA is packaged into the
phage capsid.
Linkage relationships can be assessed by co-transduction.
Example Problem: The linkage of three genes in Escherichia coli is studied by cotransduction. Bacteria
of the genotype a b c are infected with transducing particles obtained following phage infection of
- - -
bacteria with the genoytpe a b c . Using appropriate selection techniques, cells transduced for the a
+ + +
locus are identified and then tested further to determine how many of them have been transduced for one
or both of the other loci. The genotypes and frequencies of the transductants are given below:
Class Genotype Frequency
1 a b c 92
+ + +
2 a b c 4
+ + -
3 a b c 154
+ - +
4 a b c 750
+ - -
a) Is b or c closer to a?
b) Why is class 4 the most frequent?
1
Fundamental Genetics Barbara B. Sears
Lecture 8 - Introduction to Gene Regulation: the lac operon of bacteria
Vocabulary:
structural genes negative control domain constitutive repressor
regulatory genes inducible operator uninducible inducer
positive control repressible inducer operon catabolite
I. Overview of Bacterial Gene Regulation
A. Main control of gene expression is at the level of transcription.
B. Coordinate expression of multiple genes through:
1. Dispersed genes with same promoter sequences & regulatory factors
2. Operons: one promoter many genes -- one mRNA
promoter argA argB argC argD
Translation of a message carrying multiple reading frames may occur in two different ways:
(1) multiple ribosome binding sites
(2) one ribosome binding site
C. Some gene products needed at all times; others needed only occasionally.
1. Constitutive gene expression


2
2. Regulated gene expression
Cis-acting regulatory elements
promoter (P)
operator (O)
Trans-acting regulators:
repressor, inducer, transcription factor
Transcription regulators have DNA-binding domains, such as:
a) positive versus negative control - terms describe whether the regulators stimulate or
inhibit transcription
b) inducible versus repressible operon
default position is off
default is on
3
III. The lactose operon: an example of inducible gene expression
A. Sensing and responding to availability of sugars in the environment
1. Medium contains glucose >
2. If no glucose, but complex sugars (such as lactose) present >
3. Neither simple nor complex sugars present >
B. Expression of the lac operon
1. Structural genes 2. Regulatory elements
lacZ Cis-acting: Trans-acting:
lacY promoter (P) lacI gene encodes the repressor
lacA operator (O)
3. No lactose: structural genes turned off because the repressor protein binds the operator, and
blocks the path of RNA polymerase
4. Lactose present: allolactose acts as inducer: The repressor binds allolactose and changes
shape, such that it no longer binds the operator. As a consequence, RNA polymerase can
transcribe the operon, and it is turned on.
4
Summary of wild-type phenotype:
Gene Protein Product
No Glucose
No Lactose + Lactose
lacZ -galactosidase
lacY permease
lacA transacetylase
C. Mutations in structural genes
Missense mutations - usually a single gene product is defective or non-functional
Nonsense mutation
Polar mutation
Presence of gene product, when glucose is absent from the media
-galactosidase permease transacetylase
Genotype
No Lactose + Lactose No Lactose + Lactose No Lactose + Lactose
lacZ lacY lacA

-
lacZ lacY lacA

-
lacZ lacY lacA
polar
5
D. Regulatory Mutations
1. Constitutive Expression
lacI --> lacI
-
repressors operator binding site is altered so that it no longer binds the operator
lacO --> lacO
c
operator binding site is altered so that the repressor can no longer bind it
6
2. Uninducible Mutations
lacP --> lacP
-
promoter recognition site changed such that RNA polymerase no longer recognizes it.
lacI --> lacI
s
repressor no longer binds lactose, so it is never removed from the operator
7
IV. A positive regulatory response also exists for the lac-operon.
glucose present: lac-operon off (Catabolite Repression).
glucose not present: (i.e., all the circumstances discussed above) a positive regulator [catabolite
activator protein (CAP)] stimulates transcription
V. Mutations in structural and regulatory genes can be analyzed by complementation.
Plasmids, such as the F, can be used to create merodiploid bacterial cells.
(Try to figure out the phenotypes of the following constructs...)
Genotype of
Recipient
Genes carried
by plasmid
Presence of -galactosidase activity (glucose absent)
Lactose Present Lactose Absent
I P O Z -
+ + + +
I P O Z -
+ + - +
I P O Z I
+ + + - +
I P O Z -
+ + c +
I P O Z P O Z
+ + c + + + +
I P O Z -
+ - + +
I P O Z P O Z
+ - + + + + +
I P O Z -
s + + +
I P O Z I
s + + + +
I P O Z I P O Z
s + + + + + c +
What if glucose is present?
1
Fundamental Genetics Barbara B. Sears
Lecture 9: Eukaryotic genome organization & control of gene expression
Vocabulary:
acetylation methylation phosphorylation insulators
I. Major differences between eukaryotic and bacterial gene regulation
Bacteria Eukaryotes
Gene organization operons
Cotranscription yes
Nucleosomes no histones
Main level for regulation of
gene expression
transcription
II. Many levels of control in eukaryotes
2
A. Modifications in chromatin structure
1. Acetylation of histones
2. Methylation of DNA
3. The relaxing of chromatin is observed by an increase in DNaseI sensitivity
3
B. Transcriptional control
1. repressors
2. activators
& enhancers
Which activators act in trans?
Example of a eukaryotic activator protein:
GAL4 of yeast
3. Insulators: block enhancers
4
4. Coordinated transcriptional control
Genes that should be co-expressed may share 5' regulatory sequences
A single gene may have multiple regulatory sequences
C. RNA processing as a regulatory mechanism
Alternative splicing
5
D. RNA stability
1. mRNAs from different genes have different stabilities
2. Stability affected by: 5' cap, polyA tail, 5' UTR, 3' UTR
E. RNA silencing
1. One silencing pathway 2. Another silencing pathway 3. Another results in
is via antisense: results in degradation of mRNA DNA methylation
F. Translational control
Storage of messages for translational burst:
Transition of unfertilized > fertilized egg
Response to environmental or physiological signals
Translation of message for iron-binding protein
6
G. Post-translational control
Various protein modifications can affect function:
Cleavage
Trimming
Addition of:
Acetyl groups
Phosphate groups
Carboxyl groups
Methyl groups
Carbohydrates
Folding
Scrapie, Cruetzfeldt-Jakob disease, Mad cow disease
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 10: Meiosis and mitosis; Monohybrid and Dihybrid Crosses
Vocabulary:
chromosome sister & non-sister spindle P generation
1
chromatid centromere microtubules F generation
2
chromatin kinetochore genotype F generation
monohybrid cross recessive allele phenotype homozygote
testcross dihybrid cross dominant allele heterozygote
backcross true-breeding line incomplete dominance
I. Nuclear Division
A. Overview of mitosis
B. Meiosis
Excerpts from Meiosis I: Excerpts from Meiosis II:
2
C. Kinetochore Structure differs between Mitosis and Meiosis I.
Class Exercise: Pairing and segregation of chromosomes in Meiosis I and Meiosis II
II. Simple genetic crosses in diploid organisms
A. Mendels monohybrid pea crosses of true-breeding
lines
1
1. The F generation had a uniform phenotype.
2
2. In the F generation, the parental traits showed
a 3:1 segregation
3. Mendels factors = alleles
Genetic nomenclature: R vs. r
Mendels data fit perfectly with the chromosome theory of
heredity
1
F
Dominant versus recessive trait
Molecular basis of the round
versus wrinkled seeds:
Presence or absence of
Enzyme required for starch synthesis
Gametes
3
B. The Punnett square can be used to predict the outcome of crosses:
Multiplication rule for calculating frequencies: the probability of two or more independent
events occurring together can be calculated by multiplying their independent probabilities.
Addition rule: the probability of any one of two mutually exclusive events can be
calculated by adding the probabilities of the two events.
4
C. Testcross: individual of unknown genotype is crossed with another individual that is homozygous
recessive .
Example: When pure-breeding tall pea plants are crossed
with pure-breeding short pea plants, all of the F1 progeny are
short.
Which trait is recessive?
Which trait is dominant?
What is the tall phenotype(s)?
Testcross: A tall pea plant of unknown genotype is test-
crossed, and half of the progeny are short; half of them are
tall. What was the genotype of the tall plant?
D. Incomplete dominance
1
Suggest a molecular reason that the F
progeny are neither purple nor white.
2
Ratio of F progeny:
5
E. Dihybrid Crosses
Principle of independent assortment:
the alleles of genes on different chromosomes segregate independently.
6
Test your understanding of the dihybrid cross with this problem:
Tom and Jerry, two cat breeders, obtained a prize female who was solid black. They bred her to a
male cat that was brown with white spots. All the kittens were black, and half had spots. Tom and
Jerry interbred two of the solid black progeny, hoping to get litters of all black cats. In two litters,
there were 12 kittens:
6 solid black
3 solid brown
2 black with white spots
1 brown with white spots
1. Using s for the spotted gene, and b for the black/brown locus, describe the original cross in
genetic terms.
2. What is the genotype of the two black cats who were interbred?
3. Given your genetic interpretation, what numbers would have been expected?
F. Test for goodness of fit with the chi-square test
Phenotype: # observed # expected O-E (O-E) / E
2
solid black
solid brown
black with spots
brown with spots
Sum:
7
Chi Squared Table:
Interpreting the table:
- degrees of freedom (df)
- probability (p)
- important cut-off points
- When are differences between observed and expected values significant?
- If the probability is less than 0.05, what does that mean?
- If the probability is greater than 0.05, what does that mean?
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 11 - Probability and goodness-of-fit; trihybrid crosses and branch diagrams
Vocabulary for the day:
locus trihybrid cross branch diagram chi square
degrees of freedom
Using the chi-square table...
1. If your comparisons resulted in a chi-square value of 4.0 with 1 df, what would the probability
indicate?
2. If your comparisons resulted in a chi-square value of 4.0 with 2 df, what would the probability
indicate?
Another example: A true-breeding line of eggplant with purple flowers is crossed to a true-breeding line
1 2
with white flowers. The F plants all have purple flowers. Among the 160 F progeny are 110 plants
with purple flowers and 50 with white flowers. Do the data fit a 3:1 ratio?

2
B. The branch diagram as an alternative to the Punnett Square for predicting frequencies of
offspring
To set up a branch diagram, the
frequency of each trait is initially
1
considered separately, as in this F cross:

Separate columns are used to list the expected proportions of each progeny type, and then the
multiplication rule is applied to figure the expected frequency of progeny with both traits:

3
Branch diagrams are especially useful when more than two characters are being followed in a cross.
Example: trihybrid cross
Problem: What proportion of progeny will have round, yellow seeds with a gray seed coat?
4
Test your understanding with this challenge problem:
Suppose you have a pea plant which is heterozygous at three loci (round seeds, yellow-colored seeds
with gray seed coats), and you obtain progeny from self-pollination. 64 progeny seeds having the
specified phenotypes. Are these progeny numbers consistent with Mendelian predictions?
30
6
5
5
12
2
2
2
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 12 - Quantitative Genetics
Vocabulary:
polygenic mean correlation
QTL variance additive trait
A. Discontinuous versus continuous characters
Polygenic trait - phenotype affected by many genes
Quantitative traits - controlled by more than one
locus; show a continuous range of phenotypes.
QTL = Quantitative Trait Loci
Continuous variation results when many loci are involved in defining the trait.

2
Example: Kernal color in wheat (studied by Herman Nilsson-Ehle) - determined by two loci, with equal
and additive effects on phenotype.
Each A or B adds to the color:
+ +
4 additive alleles (A A B B ) = purple
+ + + +
3 additive alleles (A A B B or A A B B ) = dark red
+ + + - + - + +
2 additive alleles (A A B B or A A B B or A A B B ) = red
+ + - - - - + + + - + -
1 additive alleles (A A B B or A A B B ) = light red
+ - - - - - + -
0 additive alleles (A A B B ) = white
- - - -
The effect of each allele is additive.
3
Additive traits may also be affected by dominance or by gene interactions.
Additive - each allele results in a regular increase or decrease in a phenotypic value
A A = 4, A A = 5, A A = 6
1 1 1 2 2 2
Dominance - when the heterozygote produces a phenotype resembling one of the homozygotes
A A = , A A = , A A =
1 1 1 2 2 2
Genic interaction - when the influence of a gene at one locus depends on the genes at another
locus (epistasis)
A A = , A A = , A A =
1 1 1 2 2 2

Examples of Quantitative Traits
4
B. Statistical measurements that help describe patterns of variability in quantitative traits
1. Mean - average of the values
2. Variance (s ) - sum of difference between the
2
mean and all values, divided by sample size. The
higher the value, the more variable is the
population.
3. Standard deviation = %s
2
4. Correlation coefficient shows if there is an association between variables
An example:
5
Edward East did the first statistical study of
quantitative inheritance:
C Quantitative traits are very subject to environmental variation
1. Environmental effect can cause the phenotypes to be less precise
6
2. Sometimes individual genotypes may respond differently to the environment
D. Tremendous changes can occur in quantitative traits u
nder strong selection.
7
Corn kernel oil content has been altered by plant breeders through generations of selection:
The response of a population to selection may level off when genetic variability is exhausted.
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 13: Sex determination and sex linkage; sex-influenced and sex-limited
Vocabulary
sex chromosomes heterogametic sex hermaphroditism nondisjunction sex-linkage
autosomes homogametic sex monoecious hemizygous sex-limited
Barr Body haplodiploidy dieoecious sex-influenced
A. Genetic basis of sex determination:
1. Environmental impact on sexual differentiation
some fish, crocodiles, turtles, limpets
2. Expression of both sexes in one individual:
hermaphroditism in plants
monoecious
vs.
dioecious:
sequential hermaphroditism in limpets
B. Many animals have a chromosomal system for sex-determination
1. Sex determination by Y chromosome: Humans / Mammals - a review from recitation material
homogametic sex
heterogametic sex
sex chromosomes
Y chromosome carries male-determining gene
autosomes
dosage compensation for X-linked genes
X-inactivation
Barr Body - lyonization or heterochromatinization
Examples:
tortoiseshell cat
anhidrotic ectodermal dysplasia
2
Incorrect segregation of the human sex chromosomes in meiosis can result in syndromes:

The meiotic errors are due to nondisjunction of the sex chromosomes:
2. XX-XO system of sex determination in grasshoppers
3. ZZ-ZW system of sex determination in birds, some amphibians & fish
homogametic sex: males
heterogametic sex: females
3
4. Haplodiploidy system of sex determination in Hymenopteran insects
female: diploid
male: haploid
5. Sex chromosome : autosome ratio as basis of sex determination in Drosophila
C. Sex Linkage
sex-linked
X-linked
Y-linked
Most genes on the X-chromosome: absent from Y-chromosome.
XY individuals are hemizygous for those genes.
Drosophila melanogaster and X-linked traits
example: white eye locus
alleles: X wild-type, red eye
+
X white eye
w
Y or / no allele
4


5
B. Sex-influenced and sex-limited characteristics
1. Examples of Sex-influenced traits
... pattern baldness
... bearded allele in goats
Note: different penetrance of trait in male & female
penetrance: percentage of individuals having a
particular genotype that express the expected
genotype
complete penetrance
incomplete penetrance
6
3. Sex-limited traits: Autosomal genes whose expression is limited to one sex
e.g., cock-feathering in chickens
Problem: Red-green color blindness in humans is X-linked, where c (color blindness) is recessive to
normal vision c .
+
1) What are the possible genotypes of a color-blind female and a normal male?
2) If this couple had an extremely large family, what proportion of their male and female offspring would
be color blind?
1
Fundamental Genetics Barbara B. Sears
Lecture 14 - Exceptions to the standard dominance & recessive relationships
Vocabulary:
penetrance codominance epistasis penetrance
expressivity incomplete dominance lethal alleles
A. Phenotype does not always reflect the genotype.
1. Penetrance
Polydactyly is a human trait that shows both
variable penetrance AND expressivity:
....Expressivity is the extent to which a trait is
phenotypically expressed.
2. Environment may affect phenotype development
Temperature sensitive alleles
example 1: vestigial wings
example 2: himalayan fur
2
3. Some genetic diseases of humans can be prevented by controlling the environment
example: phenylketonuria (PKU): inability to metabolize phenylalanine
B. Degrees of dominance
1. Dominance
Example: flower color
2. Incomplete dominance
Example: eggplant fruit color
3. Codominance

Example: AB blood types
Genotype Phenotype
I I ___ antigens
A A
I I ___ antigens
B B
I I ___ antigens
A B

3
Sometimes, several descriptions are appropriate:
Example of Sickle cell anemia:
Homozygous Hb Hb has red blood
S S
cells that take a sickle shape
When the hemoglobin proteins are
examined on a gel, the Hb-A and Hb-S
can clearly be differentiated.
C. A locus may have more than two alleles
1. ABO blood groups
2. Duck feather patterns
feather pattern alleles:
M mallard
M restricted
R
m - dusky
d
M > M > m
R d
4
D. Epistasis
Example 1: fruit color in pepper
Example 2: Squash color
W__yy_ white
ww Y__ yellow
ww yy green
Example 3: comb shape in chicken

walnut comb rose comb pea comb single comb
Example 4: Coat color in dogs
Labrador retrievers:
B_E_ black
bbE_ chocolate
B_ee yellow
bbee yellow
5
2. Epistasis can result when gene products affect the same biochemical pathway.
Example: squash color
Example: snail shell color
3. Genes can interact in different ways, altering the phenotypic ratios
6
D. Lethal Alleles
when homozygous, these alleles are lethal
Consequence:
skewed ratios of progeny
absence of a progeny class
Problem: Suppose there is a sex-linked recessive lethal allele in mice, named rl.
A) Using proper genetic notation, write out the genotypes for a cross between a heterozygous
recessive female and a wild-type male.
B) From the above cross, what will be the ratio of the progeny? Be specific about both the
genotypes and phenotypes.
1
Fundamentals of Genetics Barbara B. Sears
Lecture 15 - Cytoplasmic Inheritance
Vocabulary:
organelle endosymbiosis vegetative segregation maternal inheritance
chloroplast reciprocal cross cytoplasmic inheritance "non-Mendelian" heredity
mitochondrion sexual dimorphism hetero- vs. homoplasmic extranuclear inheritance
A. Basic features of organelle genomes and organelle division
1. Organelles are polyploid, at several different levels.
2. Organelles divide by fission
3. Organelle DNAs are randomly partitioned to the daughter cells.
2
B. Features of chloroplasts and mitochondria reflect their endosymbiotic origin.
1. Many bacterial features have been preserved in these organelles:
organization of DNA
coupled transcription/translation
operon organization
gene sequences
2. Many genes have been lost from the organelle genomes and/or transferred to the nucleus.
a) Both organelles contain much smaller genomes than their free-living ancestors.
b) Many proteins:
Nucleus -------------> Cytoplasm --------------------> Organelles
c) Some genes moved long ago, but some relocations are on-going
3
C. A Quick Look at Organelle Genetic Systems
1. Chloroplasts
a. Chloroplast genomes:
-encode about 120 genes
- range in size from about 120,000 to 200,000 bp (120-200-kb).
- some non-photosynthetic parasitic plants have lost dozens of chloroplast genes, although
they have retained the organelle
2. Mitochondrial genomes are quite variable in size and gene content.
a) Ancestral versus derived genomes
-The smallest genomes encode only 13 polypeptides, two rRNAs and 22 tRNAs.
-The fungal genomes encode a few more polypeptides, and have many introns.
-The largest genomes (plant mtDNAs) encode many more polypeptides, have introns,
and gene sequences are more bacterial
4
b) Many mitochondria use an alternate genetic code
Codon
Universal
Code
Amino Acid specified by mitochondria of:
Vertebrate Invertebrate Ascidian Yeast Plants
UGA STOP TRP TRP TRP TRP STOP
AUA ILE MET MET MET MET ILE
AGA ARG STOP SER GLY ARG ARG
AGG ARG STOP SER GLY ARG ARG
CUN LEU LEU LEU LEU THR LEU
References: T.D. Fox (1987) Ann Rev Genet 21: 69
Jukes & Osawa (1990) Experientia 46:1117-26.
If the following reading frame came from human mitochondria, what would be the protein sequence?
If that reading frame was transcribed and translated in E. coli, what would be the sequence?
AUG CUA CUC AUA UGA AGA
Consequence of the change in the genetic code:
D. RULES OF CYTOPLASMIC INHERITANCE:
1. Differences in reciprocal crosses
a. Parents make unequal contributions of extranuclear genes.
b. Often (but not always), solely maternal transmission is observed.
5
2. Vegetative segregation ("sorting out")
Contrast between nuclear and organelle genes in terms of stability of a mixed state
heteroplasmic
A a
homoplasmic
Once a pure cell line has segregated, its
progeny cells are forever homoplasmic.
3. Examples of Organelle (non-Mendelian) traits:
Example 1: In animals, some diseases (optic neuropathy or muscular degeneration) are caused
by defective mitochondrial function in muscles and nerves.
Rule 1: Differences in reciprocal crosses:
In most cases, animal mitochondria are inherited from the maternal parent, although when
one looks carefully, a small number of mitochondria from the male parent can be found.
Rule 2: Vegetative segregation:
Defects in mitochondrial function would often be lethal if homoplasmic. When mutations in
mtDNA occur, they are usually only found in heteroplasmic cells. If transmitted to the progeny,
it is through heteroplasmic gametes. Oddly, defective mitochondria accumulate with age.
6
Example 2. Chloroplast traits in land plants
a) phenotype: variegation - a mosaicism of white and green tissue.
BUT, OTHER THINGS CAN CAUSE LEAVES TO BE MOSAIC!
To rule out a viral origin >
To test for a nuclear-location of a mutation ---->
b) Example of the Four-oclock plant, studied by Carl Correns:
Rule 1: Differences in reciprocal crosses:
About 70% of plants have exclusively maternal inheritance
of chloroplasts.
Rule 2: Vegetative segregation:
When mutations arise, or when biparental inheritance of
chloroplasts occurs, the different chloroplast types sort out.
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 16: Linkage and recombination in eukaryotes
Vocabulary:
linked genes crossing-over coupling genetic distance
complete linkage chiasmata repulsion map units
linkage group recombination centiMorgans (cM)
A. Mendels Law of Independent Assortment applies only to loci that are on different chromosomes.
1. Genes that are on different chromosomes are unlinked: they segregate independently.
Example: Two equally possible outcomes of meiosis in a cell of genotype Gg Hh:
2. If two loci are completely linked, then alleles at those loci are always inherited together
Parents:
GG HH x gg hh
1
F Gg Hh in meiosis:
meiotic products
from cis-
conformation
Parents:
GG hh x gg HH
1
F Gg Hh in meiosis:
meiotic products from
trans-conformation
In a dihybrid cross, independent assortment would give a 9:3:3:1 ratio... How would complete linkage
affect progeny ratios?
2
3. Incomplete linkage:
4. Terms used to describe recombination events: cross-over
chiasma (plural: chiasmata)
5. Consequences of recombination:
a) Recombination between non-sister chromatids will produce two different types of recombinant
chromatids.
b) The closer two genes are, the less likely recombination will occur between them.
c) Maximum 50% recombination between any two genes.
d) Linked genes cosegregate, resulting in more progeny with the parental genotypes and fewer
progeny with recombinant genotypes than would be recovered from unlinked genes.
6. Genetic notation for linked genes:
Instead of Gg Hh: GH or GH/gh
gh
3
B. Recombination frequencies can be used to calculate a genetic distance between two genes
# Recombinants x 100 = % Recombination = map units or CentiMorgans
Total # Progeny
Example:
Suppose you have two true-breeding lines of tomato: one has smooth fruit and is tall (PP DD) and
1
the other has hairy fruit and the plants are dwarfed (pp dd). When these lines are crossed, all the F
1
progeny have smooth fruit and are tall. When a test cross is performed with the F , the following progeny
are obtained:
485 smooth fruit, tall
18 smooth fruit, dwarf
22 hairy fruit, tall
475 hairy fruit, dwarf
Use a chi square test to determine if the progeny data indicate linkage.
If so, determine the genetic distance between the two loci.
Take these steps to solve the problem:
a) Its always a good idea to write out all relevant genetic notations.
1
Cross of Parents: F progeny: Test cross:
b) Expected frequencies for independent assortment:
PD Pd pD pd
pd
c) Chi-squared test:
4
To determine the genetic distance, you need to assess the frequency of occurrence of recombinant
progeny.
How do these numbers apply to the products of meiosis shown below?
Frequency:
5
C. Impact of Double Crossover Events on Map Distance
If a double crossover (d.c.o.) occurs between two loci, it will have the
impact of reducing their genetic distance from each other.
Therefore, a genetic map distance between close genes is more
accurate than those between distant genes.
D. Assembling a gene map from recombination frequencies
Map distances between pairs of genes can be used to assemble genetic maps.
Use the following data to make a map:
Sturtevant's data for genes
on the X chromosome in Drosophila
Gene1 Recomb
Gene 2
Frequency
Map Distance
(cM)
yellow (y) .01 1.0
white (w)
yellow .322 32.2
vermilion (v)
white .297 29.7
vermilion
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Practice Problem
In cucumbers, smooth fruit (t) is recessive to warty fruit (T) and glossy fruit (d) is recessive to
dull fruit (D). These two genes are located 16 cM apart from each other. Suppose a
heterozygous plant, in which the dominant markers are located in coupling, is test-crossed.
What types and proportions of progeny will result from this test cross?
1
Fundamentals Genetics Barbara B. Sears
Lecture 17 - Chromosome Variation: rearrangements
Vocabulary:
metacentric acrocentric inversion duplication acentric chromosome bridge
submetacentric telocentric translocation deletion dicentric position effect
karyotype
I. Terminology for chromosomal structures karyotype:
metacentric
submetacentric
acrocentric
telocentric
II. Types of changes in chromosome structure
A. Overview:
2
B. Duplications and deletions
1. Consequences of duplications and deletions:
Large duplications or deficiencies > Non-viable gametes (or zygotes)
Small duplications or deficiencies > genetic imbalance
Example: Bar eyes of Drosophila
3
2. Duplications and deletions can be caused by unequal crossing over.
3. Individuals heterozygous for a deletion or duplication will have a chromosomal region that
will not pair during prophase I.
C. Inversions
1. Two major classes of inversion:
4
2. Consequences of Inversions:
If an inversion chromosome is heterozygous and crossovers occur within the inversion,
deletions or duplications will result
Pericentric inversion:

Paracentric inversion:
Some of the resulting gametes will have deletions or duplications.
If dicentric chromosomes result, a chromosome bridge will occur in meiosis.
A centric chromosomes will be lost.
5
D. Translocations
1. Types of translocations
2. Consequences of translocations:
a) If a translocation chromosome is heterozygous,
unique pairing can be observed in meiosis.
tetravalent pairing:
b) Meiotic segregation of the translocation chromosomes is governed by homologous
centromeres going to opposite poles.
Note: Your textbooks Fig. 9.17 shows an adjacent-2 pattern of segregation which is
rare.
c) Depending on the segregation of the homologous chromosomes, the meiotic products
may have gene duplications and/or deficiencies.
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E. Genetic & evolutionary impact of chromosomal rearrangements
a) Evolutionary divergence is promoted by chromosomal rearrangements
b) Gene expression can be altered by chromosomal rearrangements
position effect
alteration of normal tissue-specificity for gene expression
One cause of leukemia is a
reciprocal translocation involving
chromosomes 9 and 22.
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 18 - Variation in Chromosome Number
Vocabulary:
aneuploid nullisomic trisomic autopolyploid triploid unreduced gametes
disomic tetrasomic monosomic allopolyploid hexaploid multivalents
tetraploid homeologous
I. Overview: Two major types of variation in chromosome number:
aneuploidy polyploidy
II. Aneuploidy
A. Aneuploids are produced through nondisjunction.
2
Nondisjunction can also occur during mitosis, producing a mosaic:
B. Aneuploidy in humans
1. Aneuploidy can occur for autosomes or sex chromosomes
2. Genetic imbalance is responsible for developmental problems
Case Study: Downs Syndrome
Trisomy 21
OR
Translocation of chromosome 21
3
C. Aneuploidy in plants is tolerated better than in animals
Jimson weed example:
12 chromosomes
D. Meiotic segregation is abnormal in aneuploids
What will be the genetic ratio?
Keeping track of chromosome segregation in an aneuploid: the hat trick
4
III. Polyploidy
A. Polyploids are formed after the total failure of meiosis or mitosis.
B. Polyploidy is not uncommon.
1. In plants:
2. In humans:
Spontaneous abortions
5
C. Allopolyploidy - chromosome sets from different species
1. Production of allopolyploid through mitotic or meiotic
nondisjunction
2. Once the allopolyploid is produced, the homeologous
chromosomes from the two sets of parents are divergent
enough that they assort independently.
6
D. Autopolyploidy - all chromosome sets from the same species
1. In autopolyploids, the homologous chromosomes from the two parents are not divergent and can
pair.
2. Meiotic consequence: multivalents can form
Example Problem: Suppose a new autotetraploid has the alleles A A a
a carried by homologues. What would be the types and ratios of ga
metes produced by the tetraploid?
Goalpost tip for figuring out gametes:
1
Fundamental Genetics Barbara B. Sears
Lecture 19 - Human Genetics & Pedigree Analysis
Vocabulary:
proband consanguinous concordance monozygotic & dizygotic twins
SNP haplotype microsatellite
Human genetics requires very different approaches.
I. Pedigree analysis of single gene traits
A. Autosomal dominant trait
e.g., Wardenburg syndrome
B. Autosomal recessive trait
Consanguinous mating
2
C. X-linked recessive trait
D. X-linked dominant trait
3
E. Y-linked trait

Challenge Pedigree:
4
Case Study: sickle cell anemia
Altered mobility of hemoglobin protein on gel:
The altered protein has a single amino acid change:
5
II. Most human traits are more complex.
For example: polygenic, sex-influenced, incomplete penetrance, environmental effect
A. Twin studies
B. Adoption studies
6
C. Assessments of linkage
1. Is there an association of phenotype with a haplotype?
Is the trait linked to individual molecular markers?
SNP = single nucleotide polymorphism
Microsatellite = region with many short,
direct repeats
Examples:
AAAAAAAAAAAAAAAAAAA...
CAGCAGCAGCAGCAGCAG...
N
Abbreviated as: (CAG)
An example of a Genome Scan to search for SNPs correlated to rheumatoid arthritis:
Control gene with known association:
NPL (Y axis) is a measure of Linkage >
They used 3,300 SNPs/1 cM of the human
genome map
In this paper, a total of 550 individuals from 157
families were genotyped for 11,245 SNP markers.
Fig. 2. Multipoint NPL scores for chromosomes
12, 13, 21, and X, demonstrating differences
observed in allele sharing between SNPs (solid
line) and microsatellites (dashed line).
Results point to four candidate regions.
1
Fundamental Genetics Dr. Barbara B. Sears
Lecture 20 - Population Genetics
Vocabulary:
gene pool genetic drift overdominance
inbreeding fitness underdominance
I. Overview of population genetics and evolutionary genetics
A. Genetic variability exists at three levels:
1. Within individuals (heterozygotes)
2. Between individuals within a population
3. Between populations of a species
B. Both population genetics and evolutionary
genetics focus on groups, rather than individuals
Evolution = change in gene frequency
over time
Population genetics studies the genetic composition of groups of individuals, including how the
groups genetic composition changes over time.
II. The amount of genetic variation in a population can be described through frequencies of alleles and
genotypes.
A. The frequency of an allele (f) = number of copies of the allele
Number of copies of all alleles at the locus
If you have three genotypes AA, Aa and aa (and therefore 2 alleles)...
AA A a
Frequency of A = 2(freq of AA) + 1(freq of Aa) = f + 1/2 f
2
aa A a
Frequency of a = 2(freq of aa) + 1(freq of Aa) = f + 1/2 f
2

Example Problem:
The human MN blood type antigens are determined by codominant alleles L and L . From the
M N
following numbers, calculate the genotypic frequencies:
Phenotype Genotype Number Frequency
M M L L 90
M M
M N L L 86
M N
N N L L 24
N N
Total:
Calculate the allelic frequencies:
M M M N
Frequency of M= f + 1/2 f = p
N N N N
Frequency of N = f + 1/2 f = q
Note that p + q = 1
Actual frequencies of MN blood groups in different human populations:
Population
Eskimo
Australian
Egyptian
German
Chinese
Nigerian
Genotype
MM MN NN
0.83 0.16 0.01
0.02 0.30 0.67
0.28 0.49 0.23
0.30 0.51 0.20
0.33 0.49 0.18
0.30 0.49 0.20
Allele Frequency
f(M) f(N)
0.91 0.09
0.18 0.82
0.52 0.48
0.55 0.45
0.58 0.42
0.55 0.45
III. The Hardy-Weinberg law is a mathematical model that allows deductions to be made about genotype
and allele frequencies.
A. Genotype and allele frequencies are constant from one generation to the next if:
...the population is large, randomly mating, and not affected by mutation, migration or
natural selection.
B. If a population is in H-W equilibrium, you can accurately
predict genotype frequencies from the allele frequencies
3
The equilibrium frequencies of the genotypes can be predicted by the expansion of the binomial
(p + q) = p + 2pq + q
2 2 2

AA = p
2
Aa = 2pq
aa = q
2
Practice Problem: Suppose the L blood group allele is known to have a frequency of 0.4 in a certain
M
population, predict the frequency of the L allele and the genotypes.
N
(1) Using p + q = 1, the frequency of the L allele is:
N
(2) Using the binomial expansion, the genotype frequencies are:
Suppose 200 individuals from a town actually have the following genotype frequencies:
= 20%
L L L L = 40% L L = 40%
M M M N N N
Determine if these frequencies are consistent with the towns population being in Hardy-Weinberg
equilibrium.
Use the Chi-Square test to answer this question.
=
2
obs exp (o-e) /e
2
L L
M M

L L
M N

L L
N N
A difference between using the chi-square test for transmission genetics and to test Hardy-Weinberg
ratios is that df = n - 2 in the H-W comparisons, instead of df = n - 1 .

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If the population does not fit H-W expectations, it may mean that the individuals are not mating randomly, or
it may mean that the population is being influenced by one or more evolutionary forces.
III. Factors that can alter gene frequencies
A. Non-random mating:
Positive assortative mating - preferential mating of like individuals
Negative assortative mating - preferential mating of unlike individuals
1. Positive assortative mating increases the frequency of homozygotes relative to numbers
predicted by H-W equilibrium
Allele frequencies are not altered, but genotype frequencies are.
Inbreeding
- in animals
- in humans
- in plants
Effects of self-pollination on levels of heterozygosity:
Homozygosity produced by inbreeding often leads to
reduced fitness > Inbreeding depression
5
2. Negative assortative mating has the reverse effect. It produces a higher proportion of heterozygotes
than would be expected with Hardy-Weinberg equilibrium.
Self-incompatibility systems exist in many plant species that force outcrossing.
B. Evolutionary Forces that can alter gene frequencies
1. Mutation
Most important role of mutation is in the
generation of new genetic variability that can then
be acted on by other evolutionary forces
2. Migration
The effect of migration depends on:
-the rate of migration
-the difference in gene frequency
between populations
3. Natural selection
Changes in gene frequency due to differential survival and reproduction
4. Genetic drift
Changes in gene frequency due to sampling errors