BIOL

=BIOL 202 - SLN01=

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='''LECTURE 01  BIOL202 SUMMER 2011'''=

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===='''Course information'''====

*Dr Dankort
*Writes on the board often
*In charge of the first two weeks
Course video available on webct
Genetics requires to do exercises
Lectures in S1/4 MTWTh 9:05-11:25 except Monday 16 &amp; 23
Midterm on the 16th May
All emails should have &quot;Biol202&quot; in subject line - No e-mails set up on webct
Office hours:
*Profs:
**Dankort: 9-11 AM May 6, 13, 31 (S2/2)
**Western: 9-11 AM May 20 (S2/2)
**Hipfner: 9-11 AM May 27 S2/2
*TAs: Mon, Tues, Wed &amp; Thurs 1-3pm (STBIO S2/2)
Super Strongly Recommended Text: Introduction to Genetic Analysis 9th Ed ( Griffiths, Wessler et al.)
Recommended solutions manual: MegaManual
*Interactive Genetics CD comes with it
Important dates &amp; times:
*Add/drop deadline: Thursday May 5th (4th lecture)
*Withdrawal deadline: Thursday May 12nd (8th lecture)
*Victoria Day: Monday May 23rd
*Midterm exam: Monday May 16th LEA room 132 @ 6-8 pm
*Final Exam: 1 or 2 June, date TBA
Grading scheme:
*Midterm MCQ: 30% (Lecture 1-8)
*Final: 60% (Lecture 1-15) - cumulative but emphasis on second half
*Two online quizzes: 10%
*Problem sets: 0%
*No supplemental exams
*No past finals/midterms posted - Do the online quizzes to have an idea of what the questions are like
*'''Problem-solving '''is crucial, requires a little of '''mathematical '''skills, you don&#39;t need to regurgitate the lecture notes
===='''Course Overview'''====

*Chapter 1: optional read
*Chapter 2: read
*Genetics is the only science where you can say &quot;genetics began on this specific day&quot; with '''Gregor Mendel'''
**What was known then<u> inheritable traits</u>, instead of DNA.
**Nowadays, the human genome has been sequenced and so we know much more than in the day of Mendelian Genetics
*Mendel worked with pea plants and studied '''in a quantifiable fashion''' (and that is what made him different from other scholars)''' '''how the plants inherited their traits
===='''Genetics and information transfer'''====

*Classical genetics can be done without DNA and genome analysis
*For a genetic system to work, information must be '''transferred'''.
**DNA '''encodes '''how to make tissues and how to coordinate.
**The information has to replicate and be '''passed '''from cell to cell during growth and from parent to progeny
**Information transformation cannot be error-proof. Otherwise, individuals would be identical
***Variation can occur either during the synthesis of DNA or RNA
===='''From classical to molecular genetics'''====

*How does the information go from a genotype to a phenotype?
*There is no way Watson and Crick would look for DNA without genetics
===='''The historical progression of genetics as a science'''====

*Don&#39;t bother to remember this
*human genome sequencing is significant. during the prof grad study, people could public article just by sequencing and cloning a gene. Now with the assistance of Internet, such process only takes 15s.


===='''Genetics and Medicine -- Hemophilia'''====

*Huge push to understand the genetics of diseases
*Hemophilia:
**you don&#39;t stop bleeding, you don&#39;t clot
**you can use specific proteins, soluble factors expressed by the '''liver '''to trigger a''' proteolytic cascade''' that leads to the synthesis of '''fibrin '''and that is what allows clotting
**factor''' VIII (absent in hemophilia A''') &amp; '''IX (absent in hemophilia B) targeted in hemophilia therapy'''
***However, you have to inject yourself a lot. You can develop an immune response to the injected proteins.
***Gene therapy: Use retroviruses (different ones for VIII &amp; IX) injecting to liver, to bump up genetically the levels of protein VIII and IX
===='''Genetics and Agriculture'''====

*Genetic selection based on growth speed, production (e.g. how to produce sweeter fruits), nitrogen fixage (whoever gets to fix this would get a Nobel Prize)
**nitrogen fixage.
***why important: N can leak into the river cause proliferation of agar and loss of N from solid.
===='''Approaches in Genetics'''====

*'''Phenotypes '''are different traits: short vs. tall, dumb vs. smart, black vs. white, curly vs. strait
**For Mendel it was dwarf vs. tall
*Genetics require a specific approach
**True breeding: e.g. tall offspring that are breeding from only tall ancestors.
*'''Forward genetics: '''From phenotype to genotype
**Cross different phenotypes A and B, note offspring ratios, identify gene or genes
**e.g. stubby + tall would always give tall ( tall is '''dominant''')If you take the tall children and you cross them with dwarf plants, then you observe a different phenotype etc.
*'''Backward genetics: '''From genotype to phenotype
**If you have two different genomes that differ by one gene and they have a different phenotype, then that gene plays an important role in the development of that phenotype
**if you think some gene is crucial for certain decease, then you can mutate that gene and transfer it to mice. From the expression the mutate gene to see whether there is any change in phenotype.
*Work with small organisms with fast reproductive cycles e.g. flies
*'''Methodologies in Genetics:'''
**'''probes''': separate genes, RNA or proteins by size then use probes (either phosphorylated complementary nucleotides for genes and RNA or antibodies for proteins)
**'''array technology''': allows to sample the levels of expression between different RNA samples between 10000 or so genes
**'''western blots:''' cheap and easy.
**need for computer established.
===='''Phenotypes and Environment'''====

*Phenotypes are produced when genes interact with the environment (both external and developmental)
*Observe the different phenotypes of '''twins '''(same genotype) that have been separated from birth
*'''Siamese cats''': form clear spots where temperatures are low
*'''Eye color''': where environment is not place a role. No matter what the sunlight or temperature, your eye color still be the same.
===='''Ethical Issues &amp; the &quot;New Genetics&quot;'''====

*'''Eugenetics''' (legal until 1972):
**select people according to DNA fingerprint - e.g. Nazi Germany
**Critics: should insurance companies knows about your genetic characters.
*'''Embryo DNA analysis''' to detect the probability of the child to have a certain genotype (e.g. Down Syndrome)


'''Genetics prior to Mendel -- &ldquo;blending inheritance&rdquo;'''

*According to '''Aristotle''', heredity was due to the mixture of &quot;semen and menstrual blood&quot;
*Mixing idea can &#39;t explain heredity - How to explain a blue-eyed child with two brown-eyed parents?
*Parents contribute equally to the genome.(Mendel contribution).


*Single gene inheritance (law of equal segregation):
**Wild-type = the norm
***Wild type drosophila have red eyes and can fly
**Mendel used different types of lines (mutants and wild types). He started with two different plants: <u>Tall x short</u> and made sure that these two different lines of plants were '''pure breeding.''' i.e. tall x tall always produces tall and short x short always produces short. These pure breeding lines are '''homozygous'''.
***Tall x short ('''P''') = 100% tal ('''F1''')l (controlled cross: you know that outccome will be tall.
***The '''parental population P''' is the original pure breeding species i.e. tall x short. The''' '''progeny of the parental population is the '''F1 generation.'''
***Tall (TT) x short (tt) &rarr; tall (T/t)
****tall has one version of the gene or the Tall allele (T)
****T is '''dominant'''
***the true breeding really means: the one trait is always the same, say purple color. But other traits may vary, like tall/short etc.
''''''

'''Genetics analysis begins with mutants'''

**Why is there a difference in phenotypes? Two possible reasons: environmental or genetic.
**'''Mendel studied peas:'''
***first studied &nbsp;with bees: not went well
***Mendel chose to study the inheritance of characters (phenotypes) whose expression is strongly influenced by gene action:
****round vs wrinkled
****tall vs short: 16 inch vs 9 inch.
****yellow or green seed interiors
****purple or white petals
****inflated or pinched ripe pods
***Each one of these phenotypes had a binary genotype
***Peas are selfing pollination:
**** Prevent external pollination. This allowed Mendel to set up cross-pollination or selfing.
****For P, Mendel just remove the anthers and transfer pollen from other phenotype plant manually.
****And for F1, just left the anthers there and let them grow.
===='''Monohybrid cross'''====

*Monohybrid cross: cross between <u>two different organisms that differ from one trait</u> or ''locus''
*TALL x DWARF = F1 TALL
*F1 TALL x F1 TALL = 75% F2 TALL and 25% F2 SHORT. Why?
**T/T x t/t &rarr; 100% T/t
**T/t x T/t&rarr; 25% T/T, 25% t/t, 25% T/t, 25% t/T &rarr; 75% tall phenotype since T is dominant (see table below for visual representation)


T male

t

T female

'''TT'''

'''Tt'''

t

'''Tt'''

tt

*single-gene model:
===='''A single gene model explains Mendel&#39;s ratios'''====

*Mendel&#39;s study approach resembled what we did above - i.e. do crosses, observe phenotypes and conclude what allele is recessive or dominant
*F1 x P is a test cross: allows to determine the genotype of F1
*Heritable factors (genes) come in pairs (one from each parent). most of the organism are diploid composed by two set of genetic materials.
*F1 are diploid and are heterozygous (alleles may be dominant or recessive)
*Each allele has an equal chance of passing to the progeny
===='''Lessons learned from the monohybrid cross:'''====

*Equal Segregation: In the heterozygote, the two different alleles of a single gene segregate from one another in the gametes with equal probability
*Dominance: In the heterozygote, one allele (dominant) may conceal the other (recessive)
===='''Problem'''====

''Suppose that a single gene controls fruit color in mango. Yellow fruit (Y-) is dominant to red fruit (yy). &nbsp; ''

''Suppose a true breeding yellow mango plant was crossed with a red-fruited plant and the resulting F1 was selfed. &nbsp;The F2 segregated as expected. &nbsp; ''

''If one of the yellow-fruited plant was randomly selected and selfed, what is the probability that its progeny would segregate for fruit color (that is, give rise to both yellow and red-fruited plants)? &nbsp; ''

''''

* Note the terminology:

To segregate for fruit color = giving rise to two different colors = heterozygous

<u>Solution:</u>

P: RR x rr

F1: rr

F2: 3 yellow* : 1 red

i.e. 2: Rr 1: RR 1: rr (see table above)

<u></u>

If you take one yellow from F2 (*), there is a 2/3 chance that it&#39;s Rr and 1/3 that it is RR. Therefore, &#8532; of F2 x F2 will segregate for fruit color. &#8531; will NOT segregate for color because RR x F2 will always give yellow fruits.

===='''Autosomes and sex chromosomes.'''====

*Mammals:
**Default for mammal is to be female. i.e. the lack of Y determine the female.
**'''SRY''' is a transcription factor located on the Y chromosome that is responsible for the male phenotype
*Flies:
**The number of sex chromosomes determine the sex.
**The color of drosophila eyes is a sex-linked trait.
**See slide (copy/paste this later)
***theh ratio of autosome and sex link of F2 are both 3:1. But r
**The fact that there is a difference in the sex ratios suggests that the gene is located on the autosomes.
**You are encouraged to do practice problems on X-linked or Y-linked phenotypes


Problem:

If a human trait such as red-green color blindness is never passed from father to son, this is likely an indication that the allele conferring this trait is:

a) &nbsp;X linked

b) &nbsp;Y linked

c) &nbsp;Recessive

d) &nbsp;Dominant

Solution:

X-linked because sons receive the Y chromosome from the father. If the disease was Y-linked, then the son would getthe allele. A).



===='''Some single gene trait in human '''====

*Brachydactyly dominant
*Albanism recessive
*Sickle cell anemia &nbsp;(partially recessive)
*Widow&rsquo;s peak(dominant)
===='''Pedigree symbols'''====

*copy image later
===='''Cystic Fibrosis '''====

*Paradigm of human disease genetics, a classical''' autosomal recessive '''disorder
*One of the diagnosis is to lick the child&#39;s skin, if it&#39;s salty then the child probably has cystic fibrosis
*The trait often appears in the progeny of unaffected individuals. The trait can, and often does, skip generations. This is like getting &#8531; of red mangos (see the first problem).
*Males and females are equally affected PICUTRES
*Often affected individuals are inbred (on the slide, cousins)
*Let A repsent the wildtype allel and a represent the recessive CFTR mutation
*If I2 and I4 both have aa, then III5 and III6 are both heteoryzgous (Aa), this means that one of (II1 or II2) and (II4 or II5) have the recessive alleles. Most likely, II2 and II4 have the recessive allele because this disease is ''rare''.
*For the other children of generation III, we can just be sure that they have A since they don&#39;t carry the phenotype (A is dominant).
*What is the probability that generation III carries a? Cross AA and Aa
*What is the probability that IV-1 is a carrier? Cross Aa and Aa - &#8532; (mango question)




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