Transcript Document

Announcements
1. Mean on multiple choice section of exam 3 = 71%
Range from 22% - 100%; 5 people didn’t take exam 3.
2. Reminder - no labs week of Thanksgiving!
3. Be sure to get lab report guidelines for last lab report due in class Dec. 6th. We’ll be much more stringent in
grading second lab report; ask questions if unsure.
Review of lecture 33
1. First approach to determine whether a behavior has
genetic components - examine differences in behavior
between closely related organisms
2. Second approach -selection of a preferred behavior
from a genetically heterogeneous population; can trait
be transferred by genetic crosses?
3. Third approach -A single gene can control a single
behavior (but most behaviors are more complex)
4. Genetics of behavior in Drosophila - courtship
behavior and the yellow mutation
Overview of lecture 34
I. Genetics of behavior in Drosophila
II. Genetics of human behavior
III. Genetics of behavior in C. elegans
I. Some Behavioral Mutants of Drosophila
Scientists Find Warmth May Make Some Flies Gay Reuters
Nov 15 2002 10:27AM
BERLIN (Reuters) - A leading German magazine reported on Friday that
researchers have found a certain type of fly can show homosexual tendencies when
temperatures are increased above 86 degrees Fahrenheit. The monthly natural
science magazine "Geo" said researchers at the Beckman Research Institute in Los
Angeles had found the fruit fly "drosophila melanogaster" had developed
a "homosexual preference" when the laboratory temperature was increased from
about 19 degrees to above 30 degrees.
"The male flies displayed clear heterosexual activities when temperatures were at
19 degrees, but above 30 degrees their behavior changed within minutes," the
report in the December issue of "Geo" released on Friday said.
"The male flies ignored the female partners at that point and chased after their male
counterparts. As soon as the temperature was reduced again, they returned to their
original behavior."
The fruit fly, which is about 3 mm long, typically accumulates around spoiled fruit.
It is one of the most valuable organisms in biological research, particularly in
genetics and developmental biology.
The scientists that made the discovery were led by Toshihiro
Kitamoto.
II. Human Behavioral Mutations
More difficult to characterize genetic control of behavior
in humans - why?
Human Behavioral Mutations
Single
gene
Multiple
genes
• Huntington Disease (autosomal dominant)
• ** Monamine oxidase syndrome, (mental retardation &
aggression), enzymes degrade neurotransmitters.
– Typically hemizygous males (X-linked recessive)
• Lesch-Nyhan syndrome (X-linked recessive)
• Tay-Sachs Disease (autosomal recessive)
• Phenylketonuria (autosomal recessive)
• Down Syndrome (tri-21 or translocation)
• ** Schizophrenia
– 1/100
– Delusional behavior (- not depression -)
– High concordance in monozygotic twins
– Polygenic (3-6 genes)
– One on human chromosome 22
– "A Beautiful Mind", 2002 Best Picture Academy Award
• ** Alzheimer's Disease
Pedigree of family with
monoamine oxidase syndrome
Using RFLP analysis, locus mapped to X chromosome, near MAOA gene.
Learning check
1. In which gene was genetic variation observed that allowed mapping to
X chr.?
2. How would you confirm MAOA gene is involved in this syndrome in
this family?
Alzheimer's Disease
• Brain: hippocampal neurons degenerate, short-term
memory decreases as does thinking, ability to care
for oneself.
• Brain deposits called neuritic plaques and cells have
neurofibrillary tangles (best diagnosis on autopsy).
• Over 25% of those over 85 yrs have it.
• Most get the late-onset sporadic form, but some have
early-onset inherited form.
Alzheimer's Disease - cont.
Genes
• Chrom. 21, APP = amyloid precursor protein gene (-> a
protease inhibitor in the membrane)
– Incorrect processing -> ~40aa beta-amyloid.
– May poison cholinergic neurons
– The inherited mutation in some families, but also in many
sporatic cases of Alzheimer's
• Chrom. 19, apoE (apolipoprotein E) gene
– Early onset, inherited; also sporatic
– The mutation apoE4 product binds tightly to beta-amyloid
• Chrom. 14
– Early onset, inherited
• Treatment (none)
– April 2002, mice, vaccination w/ beta-amyloid helps
– Inhibitors of neurotransmitter acetylcholinesterase delay
symptoms but don't cure.
III. Genetics of behavior in C. elegans
- chosen by Sydney Brenner (1968) specifically to study behavior
- Has a relatively simple nervous system: of 959 somatic cells, 302 are
neurons; entire nervous system has been reconstructed 3-D
- Brenner’s plan was to induce a large number of behavioral mutations (how?)
and correlate aberrant behavior with structural and biochemical
alterations in the nervous system
-Three behaviors originally characterized:
- positive chemotaxis
- thermotaxis - not as much known
- generalized movement
Chemotactic response to ammonium chloride
Generalized movement mutations
Of 300 induced mutations, 77 affected movement of animal
What are two movement mutants you’ve seen in lab?
Rollers (rol): go in circles on agar plates
- defects in nerve cord or body musculature
Uncoordinated (unc): from twitching to nearly complete paralysis
- defects in nerve cord or body musculature
- many unc mutants on each of 6 chromosomes
Genetic approach to study feeding behavior
How do worms eat? What do worms eat?
Genetic approach to study feeding behavior
Isolate and characterize genes that control presence or absence, function,
and patterns of innervation of 20 neurons responsible for feeding
behavior.
1. Screen 38,000 progeny of mutagenized worms
2. Assign 52 mutations to 35 genes on all 6 chromosomes
Three phenotypic mutant classes:
eat (41 mutations) - affect nervous system function and muscle
functions
pha (2 mutations) - defects in morphogenesis
phm (9 mutations) - affect muscle contraction
Cloned genes = ion channels and signaling cascades
Avery, 1993
Genetic approach to study chemotaxis
Paper by Bargmann et al., 1993. Cell 74: 515-527.
Known at start of study:
1. in vertebrates, olfaction is used to detect presence of any volatile
organic molecule and discriminate among different molecules
2. Odorants bind to receptors in cilia of olfactory neurons and induce a
signaling cascade in the cell
Questions: 1. How specific is interaction of odorants and receptors?
2. How many receptors are expressed on a single olfactory neuron?
3. How is information about odorants trnsmitted to brain to generate
appropriate behavior?
Approach: determine whether C. elegans is attracted to volatile organic
molecules; then screen for mutants that fail to chemotax to particular
odorant; characterization of mutants will help address questions and
allow for genes involved in process to be identified
Results of Bargmann study
- tested 121 volatile organic chemicals: 50 strong attractants,
11 variable, weak attractants; 60 not attractive
Characterization of odr mutants