Download PERSONAL GENOMICS

BPS3101
Genomics
Fall 2012
Textbook:
Genomes 3rd edition by T.A. Brown (Garland, 2007)
in U. of O. bookstore and Agora bookstore
Access to Genomes 2nd edition (Wiley, 2002) at:
NCBI PubMed (www.ncbi.nlm.nih.gov/)
Search under “Books” with key words of interest
Website notes & practice questions at:
Virtual campus http://137.122.151.31/bps3101/
When large-scale...
DNA
Genome
transcription
Transcriptome
RNA
translation
PROTEIN
Proteome
What kind of cell is this?
GENOMICS - study of complete set of genes in organism
FUNCTIONAL GENOMICS - study of complete set of mRNAs
(transcriptome) in cell/ tissue/ organism
PROTEOMICS
- study of complete set of proteins in cell/ tissue/organism
“Today, we refer to genomics as a discipline that studies the structure,
function and inheritance of the genome”. Biotechnology Focus “We are living
in a Genomic World, July/August 2012, p.11
Fig.1.1 & 1.2
ENVIRONMENTAL GENOMICS (METAGENOMICS)
- study of collective genomes in an environmental community
Venter et al. Science 304:66, 2004
“…identified over one million new genes and almost 150 new types
of bacteria” from ocean water microbial populations
HUMAN MICROBIOME (METAGENOMICS)
- study of microbes in and on humans
“We have ten times as many microbial cells in our body as human
ones, and though they are tiny, that still means that a 200-pound
man is carrying two to six pounds of microbes, mostly bacteria.”
Type of
bacteria
Body location
Nature June 14, 2012
Genomic projects are usually
large-scale, collaborative efforts
Human Microbiome Project Consortium Nature 486:407, 2012
“PERSONAL GENOMICS”
- sequence analysis of the genomes of individuals
News release March 17, 2010
Glenn Close has had her genome mapped by
Illumina, one of the companies that is leading
the race in whole-genome sequencing.
Close said that she decided to take the test,
which costs $48,000 to “move science forward”.
Glenn Close
How much would you pay to have your genome sequenced?
Nature (June 24, 2010) poll of 1000 life scientists
PERSONALIZED CANCER GENOMICS
- sequence analysis of DNA from cancer cells
New York Times, July 7, 2012:
“In Treatment for Leukemia, Glimpses of the Future”
“Lukas Wartman, a leukemia doctor and
researcher, developed the disease himself.
As he faced death, his colleagues sequenced
his cancer genome. The result was a totally
unexpected treatment.”
“They fully sequenced the genes of both his cancer cells and healthy cells
for comparison, and at the same time analyzed his RNA, a close chemical
cousin to DNA, for clues to what his genes were doing.”
“And they found a culprit - a normal gene that was in overdrive, churning out huge
amounts of a protein that appeared to be spurring the cancer’s growth.”
“Even better, there was a promising new drug [kidney cancer one] that might shut
down the malfunctioning gene.”
“Dr. Wartman became the first person ever to take it for leukemia.
And now, against all odds, his cancer is in remission and has been since last fall.”
PHARMACOGENOMICS
- study of how human genetic makeup influences drug response
Designer drugs & personalized medicine
“PERSONAL GENOMICS”
- sequence analysis of the
genomes of individuals
“Careers & recruitment in Pharmacogenomics”
Nature 436:746, 2005
Pharmacogenetics & pharmacogenomics are relatively new fields
“Although frequently used interchangeably, pharmacogenetics is
often considered the study of drug response in relation to specific
genes, whereas pharmacogenomics is the study of drug response in
relation to the genome” [analyzing many genes simultaneously] .
Scott Genet. Med 13:987, 2011
EPIGENOMICS
- genome-wide study of impact of chromatin structure on
gene regulation
- heritable effects of DNA methylation, histone modification...
expression
DNA methylation
(brown circles)
no expression
• Genetically identical mice but different
DNA methylation states (eg. in regulatory
region of brown-coat-colour agouti gene)
• Diet of pregnant mother can shift
distribution of coat colour in littermates
Feinberg, Nature 447: 433, 2007
Jirtle Nature Rev Genet 8:253, 2007
METABOLOMICS
- high-throughput study of metabolites (lipids, carbohydrates,
amino acids… ) in cell or tissue
see Fig. 6.22
EVOLUTIONARY GENOMICS
- study of genome evolution and consequences
“A Deep Catalog of Human Genetic Variation”
… through genomic sequencing of different
human populations
Nature October 28, 2010
When did resistance to malaria arise in humans?
or lactose tolerance….?
Vitti et al. Trends Genet 28:137, 2012
HUMAN GENOME SEQUENCE
Watson & Crick
anniversary of discovery
of double helix (2003)
50th
Feb. 2001 - draft sequence
(some gaps & sequence ambiguities)
“Sequence and expression analysis of
gaps in human chromosome 20”
(Nucl Acids Res, in press 2012)
Oct. 2004 - “ finished” euchromatic sequence
How large is the human genome?
in base pairs (bp)
or ______ billion bp
or _________ Mbp
Mega: 106
or __________ kb
kilo: 103
2001 papers in
Nature & Science
Formally it should be kbp (since DNA is double-stranded), but often
abbreviated to kb
Whose DNA was used to obtain “the human genome” sequence?
How many genes are present in the human genome?
Trend of human gene number counts (& human genome-related milestones)
These numbers are for
protein-coding genes
“Currently, a total of 7,053 small RNAs
are annotated by GENCODE”
Nature 489:105, Sept.6, 2012
Pertea & Salzberg Genome Biol 11:206, 2010
SOME SEQUENCED GENOMES (see Tables 7.4 & 8.3)
(protein-coding)
2001 draft human genome:
Francis Collins (International
Consortium) & Craig Venter
(TIGR private company)
How many genomes have been completely sequenced?
(First year of
BPS program)
September 2000
September 2001
September 2002
September 2003
September 2004
September 2005
September 2006
September 2007
September 2008
September 2009
September 2010
September 2011
September 2012
=
=
=
=
=
=
=
=
=
=
=
=
=
43
70
100
156
218
294
422
635
843
1078
1486
2972
From GOLD - Genomes OnLine Database
www.genomesonline.org/
Eukaryotic, Bacterial & Archaebacterial
Metagenome projects also listed
Alaskan soil, New York air, human intestine...
Are genome sequence papers still receiving a lot of attention?
Nature May 31, 2012
International consortium
Nature October 27, 2011
Nature December 8, 2005
HUMAN NUCLEAR CHROMOSOMES
In somatic cells (diploid) =
46 chromosomes
2 copies of 22 autosomes
and 2 sex chromosomes
XY in males, XX in females
In gametes (egg, sperm) =
23 chromosomes
1 copy of 22 autosomes
plus 1 sex chromosome
Fig.7.5
“The nuclear genome … is divided into 24 linear chromosomes…” p.4
“The nuclear genome comprises approximately 3,200,000,000
nucleotides of DNA...” p.4
They really mean bp (base pairs) not nucleotides here...
So do not multiply this number by 2 when expressing as bp
In the genomics field, the DNA units are often “abbreviated” as:
Mb (Megabases) instead of Mbp
kb (kilobases) instead of kbp
but it’s implicitly understood that it refers to double-stranded DNA
Also, note that genome sizes are expressed as haploid state
So do not multiply the number by 2 (or 4 or 6...) when stating
“genome sizes” for diploid (or tetraploid or hexaploid...)
organisms
However, if referring to the amount of DNA in a human
somatic cell, the numerical value would be:
Where is DNA located in humans?
Mitochondrial genome
(many copies/organelle &
many mitochondria/cell)
- maternally inherited
Nuclear genome
Fig. 1.1
Fig.8.11
- mitochondrial genes are
essential for energy
production (respiration)