Lecture 1 - Biology for Computational Genetics

Question 1

What are the two forms computational formulation?

Answer 1

1. Numerically encoded input with a computable objective function
2. Numerically encoded input with a computable statistical test for significance

Question 1

What is an example of a computational form in which there is a numerical input an a computable objective function?

Answer 1

input: x is all real value
f(x) = x^2
output: x that maximizes f(x)

Question 2

What is an example of a computational form in which there is a numerical inout and a computable statistical test for significance?

Answer 2

input: the counts of each type of nucleotide in a genome
output: the probability that the nucleotides could be generated by a process that is independent and identically distributed

Question 3

What is maximum parsimony?

Answer 3

if there are multiple solutions to a problem the one involving the fewest steps is the biologically correct one
-meaning if you want to figure out is two sequences are related it is through the way that has the least steps

Question 4

What are synteny blocks?

Answer 4

show regions of homologous genes between two organisms
-direction matters for these

Question 5

What are the three steps for the computational formulation of genome arrangements?

Answer 5

1. Transform the problem into a numeric input
   a. a list of genes [1…N] and their order and orientation a permutation in another genome
   Example: A=[1,2,3,4,5,6,7,], B=[1,-7,-6,-5,2,3,4]
2. Define model
   a. let the evolutionary model be a reversal (define Ref(G,i, j) to be the reversal of elements in G from position i to position j. this reversed the order and orientation of each element
   Example: Rev (B, 2,4) = [1,5,6,7,2,3,4]
3. Define problem:
   a. given genome A and permutation B find the minimal number of reversals to transform B into A

Question 6

What is the central dogma of genetics?

Answer 6

DNA - RNA - protein

Question 7

What is a plasmid?

Answer 7

small circular genome and can encode a virus or some bacterial genes

Question 8

What has a circular genome?

Answer 8

bacteria

Question 9

What has a linear genome made up of chromosomes?

Answer 9

eukaryotes

Question 10

How many pairs of autosomal chromosomes and sex chromosomes to humans have and how many bases in total?

Answer 10

22 autosomal chromosomes
1 sex chromosome
3.2 billion bases in total

Question 11

How many angstroms and in m are DNA basepairs?

Answer 11

3.4 angstroms (1^-10m)

Question 12

How many bases is 1 full DNA twist and how many angstroms is it?

Answer 12

10.5 bases
34 angstroms (1^-9m)

Question 13

How many angstroms is one nucleosome?

Answer 13

340 angstroms (1^-8m)

Question 14

How many nm is a virus?

Answer 14

20-300nm (1^-8-1^-7m)

Question 15

How many m is a bacteria?

Answer 15

10^-6m

Question 16

How many um is a nucleus?

Answer 16

6um or 10^-6m

Question 17

How many um is a cell?

Answer 17

10um or 10^-5m

Question 18

What are the genome orders of magnitude?

Answer 18

Question 19

What is the repeat structure in the human genome?

Answer 19

-the human genome is highly repetitive with repeats spanning many scales
-50% of the human genome is repeats excluding centromeres since when you add them you get a 55% range
-the repeat structure of genomes effects computational problems such as genome assembly and read alignment

Question 20

What is a short tandem repeat or STR?

Answer 20

-repeated monomer sequence that is 2-7 bases repeated up to several hundred time
-total amount of genome is 4.3% or 138 Mbp

Question 21

What is the mutation rate of STR compared to DNA?

Answer 21

up to 10,000 time greater than ordinary DNA

Question 22

What is the societal importance of STRs?

Answer 22

since the repeats are highly mutable the odds of people getting the same sequence at a locus are low which means you can get a unique DNA “fingerprint” with only 13 loci for forensics databases

Question 23

What is the biological importance of STRs?

Answer 23

STR expansions are linked to diseases such as ALS pr Huntington’s

Question 24

What is a mobile element?

Answer 24

mobile DNA are sequences that copy themselves or hijack reverse translation system; pieces of DNA that have info encoded in them so the cell can copy them and put them back into a gene

Question 25

What is an autonomous mobile element?

Answer 25

autonomous mobile elements are sequences that encode the proteins that copy themselves; encodes for proteins that copy that very sequence of DNA - create a positive feedback loop and are often hyper methylated to terminate the positive feed back loop

Question 26

What is a non-autonomous mobile element?

Answer 26

get copied into RNA and then get spliced back but cannot do this themselves and rely on other cell machinery to do so

Question 27

What is a non-autonomous mobile element of the human genome?

Answer 27

Alu (280-350 base sequence) that have 1 million copies in the human genome

Question 28

What is an autonomous mobile element of the human genome?

Answer 28

LINE - up to 7,000 bases and is 15% of the human genome

Question 29

What is a segmental duplication?

Answer 29

a sequence that is atleast 1kb in length that is not a mobile element or tandem repeat that is duplicated with at least 90% identity elsewhere in the human genome

Question 30

How are segmental duplication drivers of evolution and disease?

Answer 30

segmental duplication drive nonallelic homologous recombination and this results in the duplication or deletion of a region

i.e. 15% of chromosome 16 is novel with respect to the human chimpanzee ancestor due to segmental duplication expansion
-1% of autism cases are linked to a deletion in a segmental duplication

Question 31

What is the binary representation of DNA?

Answer 31

A = 00
T = 11
G = 10
C = 01

represented in two bits

Question 32

How many bits make a byte?

Answer 32

8 bits

Question 33

How can the reverse complement be computed?

Answer 33

the NOT or !A operator

Question 34

How to represent all combinations of nucleotides of length 8?

Answer 34

4^8 combinations

Question 35

How much memory is required to store a 4G or 4 billion base genome with binary encoding?

Answer 35

one byte = 8 bits
one base = 2 bits
4 bases = one byte

1 billion bytes

Question 36

What is included in the anatomy of a gene?

Answer 36

5’ untranslated region to an ORF to another 3’ untranslated region

Question 37

What do enhancer or silencer’s do?

Answer 37

increase or decrease the amount of RNA transcribed through DNA binding proteins where certain proteins or Transcription Factors bind to the DNA