# *Genome 2 Phenome 4 Non-Biologists Workshop*: Molecules, March 18 2021

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## Molecules, central dogma, phenotypes
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### Learning Objectives:

* Define what a cell is
* Understand the "Central Dogma" of molecular biology
* Connect DNA → genotype → phenotype

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### Question 1:
**Describe an example (that is NOT the one you just saw) in which two identical genotypes produce different phenotypes.**

* Breakout Room 1:
* Changing the environment; twins being raised in different families.
* Breakout Room 2:

* Twin humans. Lots of different phenotypes, such as disease, height.

* Breakout Room 3:
* growing a plant in different climates or locations
* human twins raised in different social/economic settings

* Breakout Room 4:

* Monozygotic twins having different production performance in pigs, sheep and goats

* Breakout Room 5:
* Different environments can lead to different phenotypes. Twins, separated at birth, one smokes starting at age 12. Shorted lifespan.

* Breakout Room 6:
* rats with same genotypes with different colors

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* Maternal diet causing differences in weight of offspring

* Breakout Room 8:
* Same genetics + different environment = different phenotype (shorter plants because of lower soil nutrition) ​
* Breakout Room 9:
* Tree Height based on altitude (shorter tree at higher altitude)
* Higher number of hemoglobin in the blood of indviduals who live at higher altitude
* Breakout Room 10:
* Different nutrition intake, for example high protein vs low protein can cause different phenotypes.
* Breakout Room 11:
* Twin sheep reared in different environments
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* Breakout Room 12:

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### Question 2:
**Which do you think might have a more severe effect on a gene, changing a single base from a G to an A or removing the G altogether? Explain your answer.**

* Breakout Room 1:
* Removing G altogether will have a severe effect. It will shift the reading of the frames.
* Breakout Room 2:
* We're unsure - if the molecular machinary can detect deletions and cause, say, apoptosis, then deletion might be preferable. If changing cannot be detected then this may have adverse or negative effects on the phenotype.

* Breakout Room 3:
* both. Changing the codon in either instance will change outcome
* will changing one make more of a difference than removing one completely?

* Breakout Room 4:
* Deletion can change the frameshift which can have more drastic change
* Depending on the location of the sequence the outcome may vary
* Breakout Room 5:
* Removing a nucleotide. The reading frame changes causing the amino acids to be different.
* Breakout Room 6:
* removing the G chnages the pairing

* Breakout Room 7:
* Changing a single base only changes a single amino acid while removing will changing everything after that base

* Breakout Room 8:
* A deletion will usually be more detrimental because it will cause a frameshift during mRNA translation. It can change the protein makeup of the entire protein, often resulting in loss of function.But a base pair change can at times have a dramatic effect.
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* Breakout Room 9:
* A deletion will cause a frame shift downstream of the deletion, which changes all subsiquent amino acid translation.

* Breakout Room 10:
* The changing of a base and its severity depends on the location of the base in the codon. Whereas a deletion can potentially cause a frame shift, which can change the reading frame of the gene.
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### Question 3:
***True story*…Humans have recently synthesized four new, ADDITIONAL DNA bases (P, Z, B and S) that have similar, strict base pairing rules among themselves (P -- Z and B -- S). What do you think an eight base DNA code has the potential to allow?**

* Breakout Room 1:
* More information and variability.
* Breakout Room 2:

* You can only encode for the amino acids - more bases won't allow for additional synthesis of amino acids, unless there are more amino acids in this imagination.

* Breakout Room 3:
* it will become very complicated to predict outcomes
* More phenotypes

* Breakout Room 4:
* The 4^3 codon table will expand to 8^3 possibilities. New synthetic amino acids can be developed.

* Breakout Room 5:
* If we can translate them with custom translational machinery, we could have new amino acids in our proteins. Could also lead to more mutations as there are more "letters" for changes.

* Breakout Room 6:
* magnified information produced from the 8 bases rather than 4

* Breakout Room 7:
* A lot more codons are possible with 8 bases

* Breakout Room 8:
* More potential amino acids or more combinations (permutations) for amino acids;
* Breakout Room 9:
* You could include more redundency in RNA -> Amino acid encodings or you could code for more exotic amino acids
* Breakout Room 10:
* Increased opportunity for higher levels of variation i.e. amino acids etc. It could also change accessibility of the DNA and how it is read.
* Breakout Room 11:

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### Question 4:
**Gene annotation software looks for particular DNA sequence characteristics occurring together to define genes de novo. What are potential pros and cons of this approach?**

* Breakout Room 1:
* Pros: straight forward approach, and easy to find new characteristics in the sequence.
* Cons: The DNA sequence has to be in a proper format and correctly assembled, and the software has to be contantly updated with the new data that it sees.
* Breakout Room 2:

* Finding specific bases together allows for easy identification of certain known genes. However, this is not an exact science and relies on prediction and correlation

* Breakout Room 3:
* Pro: looking at sequence
* Con: big data complexity

* Breakout Room 4:

* Breakout Room 5:
* Pros: Computaitonal predictions are fast and cheap (good),
* Cons: Have to consider have false positives. Could test in the lab to verify predictions, but work is expensive.

* Breakout Room 6:
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* Breakout Room 7:
* Pros: You can figure out where genes are on a DNA strand
* Cons: We may not find all the genes

* Breakout Room 8:
* Pros: Can detect heritable genetic differences between individuals and associate them with phenotypes.
* Cons: Have to take into consideration: introns; gene sequence doesn't necessarily = translation; regulatory genes; artifacts w/o function.
* Breakout Room 9:
* Pros: The algorithm is conceptually straight forward, and can be optimized
* Cons: Trying to define new genes based on its location does not take into account for structural variation
* Breakout Room 10:
* Pros:
* Cons: The program is only as good as the annotation you have, so the software may not be able to identify all characteristics.
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**Glossary/Jargon** (for terminolgy you don't know)

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**Resources for Further Learning:**

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