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/

GENOMICS - study of complete set of genes in organism

Fig.1.1 & 1.2

DNA

RNA

PROTEIN

FUNCTIONAL GENOMICS - study of complete set of mRNAs (transcriptome) in cell/ tissue/ organism

PROTEOMICS - study of complete set of proteins in cell/ tissue/organism

Genome

Transcriptome

Proteome

transcription

translation

When large-scale...

What kind of cell is this?

“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

ENVIRONMENTAL GENOMICS (METAGENOMICS)

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

- study of collective genomes in an environmental community

HUMAN MICROBIOME (METAGENOMICS)

Nature June 14, 2012

“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.”

Body locationType of

bacteria

Human Microbiome Project Consortium Nature 486:407, 2012

- study of microbes in and on humans

Genomic projects are usually large-scale, collaborative efforts

“PERSONAL GENOMICS”

Glenn Close has had her genome mapped by Illumina, one of the companies that is leading the race in whole-genome sequencing.

News release March 17, 2010

Glenn Close

- sequence analysis of the genomes of individuals

Close said that she decided to take the test, which costs $48,000 to “move science forward”.

Nature (June 24, 2010) poll of 1000 life scientists

How much would you pay to have your genome sequenced?

“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.”

New York Times, July 7, 2012:

“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.”

PERSONALIZED CANCER GENOMICS- sequence analysis of DNA from cancer cells

“In Treatment for Leukemia, Glimpses of the Future”

“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.”

“Careers & recruitment in Pharmacogenomics” Nature 436:746, 2005

PHARMACOGENOMICS- study of how human genetic makeup influences drug response

Designer drugs & personalized medicine

“PERSONAL GENOMICS”

- sequence analysis of the genomes of individuals

Scott Genet. Med 13:987, 2011

“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] .

Pharmacogenetics & pharmacogenomics are relatively new fields

• Genetically identical mice but different DNA methylation states (eg. in regulatory region of brown-coat-colour agouti gene)

Jirtle Nature Rev Genet 8:253, 2007

• Diet of pregnant mother can shift distribution of coat colour in littermates

EPIGENOMICS

- genome-wide study of impact of chromatin structure on gene regulation

- heritable effects of DNA methylation, histone modification...

no expression

expression

DNA methylation(brown circles)

Feinberg, Nature 447: 433, 2007

METABOLOMICS

see Fig. 6.22

- high-throughput study of metabolites (lipids, carbohydrates, amino acids… ) in cell or tissue

When did resistance to malaria arise in humans?

Vitti et al. Trends Genet 28:137, 2012or lactose tolerance….?

EVOLUTIONARY GENOMICS

Nature October 28, 2010

“A Deep Catalog of Human Genetic Variation” … through genomic sequencing of different human populations

- study of genome evolution and consequences

Watson & Crick50th anniversary of discoveryof double helix (2003)

HUMAN GENOME SEQUENCE

Feb. 2001(some gaps & sequence ambiguities)

Oct. 2004 - “ finished” euchromatic sequence

- draft sequence

“Sequence and expression analysis of gaps in human chromosome 20” (Nucl Acids Res, in press 2012)

How large is the human genome?

2001 papers inNature & Science

or _________ Mbp Mega: 106

or __________ kb kilo: 103

Whose DNA was used to obtain “the human genome” sequence?

in base pairs (bp)

Formally it should be kbp (since DNA is double-stranded), but often abbreviated to kb

How many genes are present in the human genome?

or ______ billion bp

Pertea & Salzberg Genome Biol 11:206, 2010

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

SOME SEQUENCED GENOMES (see Tables 7.4 & 8.3)

2001 draft human genome: Francis Collins (International Consortium) & Craig Venter (TIGR private company)

(protein-coding)

How many genomes have been completely sequenced?  

September 2000 = September 2001 = September 2002 =September 2003 = September 2004 =September 2005 =September 2006 =September 2007 =September 2008 =September 2009 =

September 2010 = September 2011 =

From GOLD - Genomes OnLine Database www.genomesonline.org/

4370100156218294422635843107814862972

(First year of BPS program)

September 2012 =

Eukaryotic, Bacterial & Archaebacterial

Metagenome projects also listedAlaskan soil, New York air, human intestine...

Are genome sequence papers still receiving a lot of attention?

Nature May 31, 2012 Nature October 27, 2011 Nature December 8, 2005

International consortium

Fig.7.5

HUMAN NUCLEAR CHROMOSOMES

In somatic cells (diploid) =

46 chromosomes

2 copies of 22 autosomesand 2 sex chromosomes

XY in males, XX in females

In gametes (egg, sperm) =

23 chromosomes

1 copy of 22 autosomesplus 1 sex chromosome

“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...

Also, note that genome sizes are expressed as haploid state

In the genomics field, the DNA units are often “abbreviated” as:

but it’s implicitly understood that it refers to double-stranded DNA

Mb (Megabases) instead of Mbp

kb (kilobases) instead of kbp

So do not multiply this number by 2 when expressing as bp

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?

Nuclear genome

Mitochondrial genome (many copies/organelle & many mitochondria/cell)- maternally inherited

Fig. 1.1

- mitochondrial genes are essential for energy production (respiration)

Fig.8.11