Heaphy 12 Genomics

Question 1

Genomics:

Answer 1

study of genomes and genome sequences
first use by Hans Winker in 1920- All the genes in a haploid set. Modern usage encompasses all the cellular DNA in an organism

Question 2

term genomics was coined by

Answer 2

Thomas Roderick for mapping sequencing and characterising genomes
1986

Question 3

Genomics Scope:

Answer 3

Viral genomics, Archaeal, Bacterial, (prokaryotic), Eukaryotic.
Species genomics, mouse, human…, mammalian, avian….,organellar,

Question 4

Metagenomics:

Answer 4

soil water ocean, human, gut, mouth, teeth,skin, object or surface such as a shower curtain.

Question 5

DNA sequencing

Answer 5

Sanger di-deoxy sequencing 1980 to date, human genome sequence, technological improvements, very accurate long sequences but relatively slow and expensive. 1000s of nucleotides per day, genomes in months or years

Question 6

DNA sequencing

capillary fluorescence:

Answer 6

Much faster, machine read

and filed straight to a computer in the 1990s

Question 7

DNA sequencing

radioactive gel-based:

Answer 7

Slow, manually read in the 1980s

Question 8

next generation sequencing:

Answer 8

2007 + , Illumina, Roche 454, ion torrent and many more technologies, short sequences, less accurate but massively parallel, millions to billions of nucleotides per day, genomes in minutes or overnight. Technology still developing

Question 9

Shotgun sequencing

Answer 9

Genome assembly relies on identifying overlapping sequences

Question 10

Human genome

Answer 10

3 billion base pairs 23 chromosome pairs

Question 11

first sequenced gene

Answer 11

bacteriophage MS2 coat protein gene 1972

Question 12

first sequenced genome

Answer 12

bacteriophage MS2, 3569 nts 1976, RNA genome

Question 13

first sequenced DNA genome

Answer 13

bacteriophage fX174, 5368 nts 1977

Question 14

first bacterial genome

Answer 14

Haemophilus influenzae, 1,830,140 nts 1995

Question 15

first eukaryotic sequence

Answer 15

S. cerevisiae, 12,495,682 in 1996

Question 16

Human genome sequence reported

Answer 16

~3.3 billion nts in 2003

Question 17

Largest genome sequence

Answer 17

loblolly pine, 22.18 billion

Nucleotides

Question 18

Genome sizes

Answer 18

E.coli 5Mb
S. cerevisiae 12.5 Mb
H. sapiens 3.3GB

Question 19

Genome sizes from graph

Answer 19

Viroids, 300 nts; viruses 3.5Kb-2.5Mb; bacteria and archaea 150Kb-10Mb;
eukaryotes 13Mb-22Gb. Free living organisms have larger genomes than
Endosymbionts. Overlap in genome sizes between domains

Question 20

Microbial

General features of genomes:
Size
form
protein coding regions
operons
RNAs
gene transfer
evolving

Answer 20

• Small
• Circular & plasmids
• Gene density high >90% (short intergenic regions, introns rare, little repetitive/ non-coding seq)
• Protein coding regions short <1Kb
• Operons w/ proctor just upstream
• few non-coding RNAs
• Frequent horizontal gene transfer
• rapidly evolving

Question 21

Eukaryotic

General features of genomes:
Size
form
protein coding regions
operons
RNAs
gene transfer
evolving

Answer 21

• Large Gb
• linear chromosomes
• gene density low <25% (long intergenic regions, introns common, repetitive non-coding seq common)
• Protein coding regions larger, 30Kb +
• Average of 3 splice variants
• many non-coding RNAs
• Infrequent HGT
• Less rapid evolution?

Question 22

What can genomics do ?

Answer 22

• everything about an organism and its developmental program
  Metabolic capabilities.
• Phylogeny: position in the tree of life
  -Disease resistance or susceptibility
• understand what life is, to create and manipulate it
• Metagenomics: how an ecosytem functions and an organisms role in that ecosystem

Question 23

importance of bioinformatics

Answer 23

Individuals & populations:

DNA-> RNA ->protein -> phenotype -> selection -> evolution

Question 24

Computational goals of bioinformatics:

Answer 24

• Learn & generalise: conserved patterns
• Prediction
  Organise & intergrate: systematic & genomic approach
  -Simulate: model gene expression
  -Engineer: construct
  -Target: mutations, drugs

Question 25

Discovering function from protein sequences:

Answer 25

- active site of trypsin- like serene proteases: GDSGG - zinc finger - structure/function - sequence similarity

Question 26

Genomic analysis

Answer 26

describes the whole organism, bioinformatics and experimentation allows us to identify individual components and to determine their functions. Development of bio building blocks enables the construction of new organisms with different properties

Question 27

Interactomes:

Answer 27

can be inferred from bioinformatic and biochemical data, redrawn as engineering circuit diagrams which facilitates biological design

Question 28

Craig Venter

Answer 28

Bacterial genomes and bacteria reduced to chemistry. 1.08Mb Mycoplasma mycoides bacterial genome similarly synthesized from chemicals, reassembled in yeast and transplanted into Mycoplasma capricolum in 2010.

Question 29

Lessons from Genomics

Answer 29

Prokaryotic cell <500 genes M. genitalium Free living prokaryote ~1500 genes Aquifex aeolicus Solibacter usitatus 10. Mb genome 10 000 genes (largest) Free living eukaryote ~5000genes S. pombe and cerevissae 15000 genes multicellular organism Drosphila C.elegans Human consciousness 20 000 genes Distinction between prokaryote cell and eukaryote cell is one of gene type and organisation and interaction- NOT NUMBER OR GENOME COMPLEXITY

Question 30

Transcriptosome

Answer 30

What genes expressed when, how much and in response to what.

Question 31

Proteome

Answer 31

What proteins expressed, when, how much, in response to what. Metabolome Glycome interactome

Question 32

Comparative genomics

Answer 32

What is conserved between species? Genes for basic processes Understand the uniqueness between different species their adaptive traits

Question 33

What makes closely related species different?

Answer 33

Analyzing & comparing genetic material from different species to study evolution, gene function, and inherited disease

Question 34

Sequence individual genomes

Answer 34

improved disease diagnostics and personalised therapies. Possible, becoming routine.