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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!

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slide1

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.

slide2

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

slide3

Overview of lecture 34

I. Genetics of behavior in Drosophila

II. Genetics of human behavior

III. Genetics of behavior in C. elegans

slide5

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.

slide6

II. Human Behavioral Mutations

More difficult to characterize genetic control of behavior in humans - why?

slide7

Human Behavioral Mutations

  • 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

Single

gene

Multiple

genes

slide8

Pedigree of family with

monoamine oxidase syndrome

Using RFLP analysis, locus mapped to X chromosome, near MAOA gene.

Learning check

In which gene was genetic variation observed that allowed mapping to X chr.?

How would you confirm MAOA gene is involved in this syndrome in this family?

slide9

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.
slide10

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.
slide11

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
slide13

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

slide14

Genetic approach to study feeding behavior

How do worms eat? What do worms eat?

slide16

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.
  • Screen 38,000 progeny of mutagenized worms
  • 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

slide17

Genetic approach to study chemotaxis

Paper by Bargmann et al., 1993. Cell 74: 515-527.

Known at start of study:

in vertebrates, olfaction is used to detect presence of any volatile organic molecule and discriminate among different molecules

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

slide18

Results of Bargmann study

- tested 121 volatile organic chemicals: 50 strong attractants, 11 variable, weak attractants; 60 not attractive