Genomics

Question 1

What has been the trend with cost of sequencing 1 human genome over the years?

Answer 1

It has dropped dramatically from $100,000,000 in 2001 to around $1,000 in 2021, with a massive drop-off in 2007-2010

Question 2

What is high throughput sequencing?

Answer 2

It is qualitative and quantitative

Question 3

How are assays used in sequencing?

Answer 3

Numerous assays that harness the quantitative power of sequencing technologies are used to understand genome function

Question 4

Genomics

Answer 4

the study of whole sets of genes, their products, and their interactions

Question 5

Bioinformatics

Answer 5

the application of computational methods to the storage and analysis of biological data

Question 6

Gene annotation

Answer 6

the process of identifying all protein-coding genes in a genome sequence and ultimately their functions

Question 7

What are some centralized resources for analyzing genome sequences?

Answer 7

NCBI, GenBank (database of sequences), BLAST (allows searching GenBank - the google of genomics)

Question 8

Is all of our DNA necessary

Answer 8

No, most of the DNA in our genomes in junk!!!

Question 9

What are the different types of variation of different genomes?

Answer 9

Single Nucleotide Polymorphisms (SNPs)
various types of chromosomal structural rearrangements (deletions, transversions etc)
Copy number variants (CNVs)
Repetitive DNA

Question 10

What is a Single Nucleotide Polymorphism (SNP)

Answer 10

a substitution of a single nucleotide that occurs at a specific position in the genome; NOT a mutation (substitutions occur at an appreciable degree within a population)

Question 11

What is Minor Allele Frequency (MAF)

Answer 11

the frequency at which the least common allele occurs in a given population
Common variants (MAF > 5%)
Rare variants (MAF < 1%)

Question 12

What is Copy Number Variants (CNVs)?

Answer 12

Loci where some individuals have one or multiple copies of a particular gene or genetic region, rather than the standard two copies
Caused by duplications and deletions
Like SNPs, may or may not have phenotypes or cause disease

Question 13

Where does CNVs stem from?

Answer 13

Many CNVs stem from segmental duplications (large blocks of 10,000 to 300,000 bp that have been copied to another region of the genome)

Question 14

CNVs vs SNPs

Answer 14

Total number: 38000 vs 14 million
Size: 100-3000 bp vs 1 bp
Type: deletions, duplication, complex vs transition, transversion,
Effects on genes: gene dosage, interruption vs missense, nonsense, frameshift
Percentage of reference genome covered: 30% vs 1%

Question 15

What are the four categories of repetitive DNA?

Answer 15

Short tandem repeats: Duplications of sample sets of DNA bases (1-5 bp)
Tandem repeats: Duplications found at the centromeres and telomeres of chromosomes that are 100-200bp long
Interspersed Repeats- DNA transposons and retrotransposons
Segmental Duplications

Question 16

What are the phenotypic effects of simple and tandem repeats?

Answer 16

STR and TR containing genes are directly involved in the generation of phenotypic variation (liquid yeast example)

Question 17

What are transposable elements?

Answer 17

segments of DNA that can move within the genome of a cell by means of a DNA or RNA intermediate

Question 18

What do DNA transposons do?

Answer 18

move through DNA intermediate; “copy and paste” or “cut and paste”

Question 19

What does retrotransposons do?

Answer 19

move through an RNA intermediate, always “copy and paste”, most abundant

Question 20

How does transposable elements impact the genome size

Answer 20

TE activity can dramatically increase genome size

Question 21

How are TEs a source of phenotypic variation

Answer 21

Insertion of Gret1 retrotransposon resulted in the loss of color of grapes (from purple to green)
Rearrangement of retrotransposon led to the revertant, colored grapes (from green to red)

Question 22

How is sequencing and comparisons of genomes made possible?

Answer 22

Through advances in genomics and bioinformatics

Question 23

What percent of human genes are conserved in other organisms?

Answer 23

Around 50%

Question 24

How does genomes vary?

Answer 24

Varies in size, number of genes, and gene density
bacteria have smaller genomes (1-6 Mb) compared to eukaryotic genomes (12-670,000 Mb)

Question 25

Demonstrate diversity through gene duplication

Answer 25

Duplication of ancestral globin gene, and many mutations and transpositions to different chromosomes allowed for gamma fetal Hgb to be created, that is more efficient than the old globin.

Question 26

Demonstrate diversity through changes in gene regulation

Answer 26

The Hox gene 7 changed from no suppression of legs to suppression of legs

Question 27

Demonstrate diversity through changes in gene loss

Answer 27

Humans used to have a yolk gene similar to chickens and monotreme, but it was lost due to the rise of traditional birth