The Human Genome

Some interesting facts

Biological system overview

Genes need to be expressed at the right time in the right place ~ 5k – 10k genes per tissue

Genes have variability, which causes a phenotype

Genes encode proteins which may be processed or modified -100k – 500k proteins

Proteins and RNAs interact in pathways and networks ~8 interactions pp

The human genome

Genome size: 3200 Mbp

http://www.ensembl.org

24 chromosomes + mitochondrion

Sequencing the genome

In 1953 James Watson and Francis Crick discovered the structure of DNA - the code of instructions for all life on earth

50 years later the human genome was sequenced by hierarchical shotgun sequencing

Sequencing the genome

The human genome was sequenced by:The International Human Genome

Sequencing ConsortiumCelera Genomics

Technique –hierarchical shotgun sequencing Draft sequences release in early 2001, but

~10% euchromatin missing and 150 000 gaps! After finishing -rereleased in 2004 with 341

gaps and covering 99% of euchromatic genome

Sequencing time period

International Human Genome Sequencing Consortium 2001. Nature 409, 860 – 921.

First human genome took ~5 years and cost ~$3 billion

Now, can sequence in a few weeks for ~$5,000

BUT: doesn’t consider cost and time for data analysis!

Size of the genome

There are 100 trillion (100,000,000,000,000) cells in your body.

There are three billion (3,000,000,000) base pairs in the DNA code within each cell.

The genome requires more than 3 gigabytes of computer storage space

Full genome done by NGS costs $100/genome per year to store

http://www.pbs.org/wgbh/nova/genome/facts.html

Interesting facts If all the DNA in your body was put end to end, it

would reach to the sun and back over 600 times (100 trillion times six feet/92 million miles).\

If unwound and tied together, the strands of DNA in one cell would stretch almost six feet but would be only 50 trillionths of an inch wide.

It would take a person typing 60 words per minute, eight hours a day, around 50 years to type the human genome.

If all three billion letters in the human genome were stacked one millimeter apart, they would reach a height 7,000 times the height of the Empire State Building.

http://www.pbs.org/wgbh/nova/genome/facts.html

Some statistics

Only 1.5% of genome is coding Other non-protein coding sequence is for other

kinds of “genes” or “lost genes” A proportion of our genome is not our own!

50% repeat regions, most of viral origin!single most common protein is the "recipe" for

making Reverse Transcriptase 99.9% of our sequences are identical

Number of human genes First estimates of between 20 000 and 150 000

genes Seems to be between 20 000 and 30 000 genes Expansion of the number of different protein

molecules due to: (a) alternative splicing (30 to 50% increase); (b) post-translational modifications (5 to 10 fold

increase) There could be about 1 million different

protein molecules in the human body

Gene numbers

2000-5000 genes

24000 genes

6000 genes

19000 genes

14000 genes

22000

21000

Latest genome build

Known protein-coding genes: 20,442 Novel protein-coding genes: 434 Pseudogenes: 15,007 RNA genes: 12,523 Gene exons: 649,964 Gene transcripts: 181,744

Protein coding genes

Many of the genes are alternatively spliced Human genes have short exons (50

codons) and long introns (10k) Average gene length is 3000bp, max is 2.4

mill We know the function of less than half of

all the genes

Comparative genomics

Comparing the human genome to others:

Organism Genome size (Mbp)

No. of genes

Human 3000 21,000

Mouse 2800 22,000

Fruit fly 180 14,000

Worm 97 19,000

Yeast 12 6000

Evolution of humans

Genes in common with other organisms

About 75% of human genes have non-human homologues, ~70% match mouse proteins

International Human Genome Sequencing Consortium 2001. Nature 409, 860 – 921.

Functional composition

International Human Genome Sequencing Consortium 2001. Nature 409, 860 – 921.

Humans have more

multifunctional genes, and genes involved in cell-cell

communication and signalling

Human genome resources

Ensembl UCSC Genome Browse OMIM –human genes and inherited

disorders dbSNP -single nucleotide polymorphisms Genetic Map at NCBI Etc.

http://www.ncbi.nlm.nih.gov