Genomics - lecture 6 Flashcards
What is the goal of the human Genome project?
Obtain the entire DNA sequence of the haploid human genome
who were the two organisations that funded the Human Genome Project?
- International Human Genome Sequence Consortium ,headed by Francis Collins
- Celera Genomics, headed by Craig Venter
Funding type and technique used by the International Human genome Sequence Consortium
- Public funding , free access to all
- Used mapping overlapping clones methods
Funding type and technique used by Celera Genomics
- private funded
- used whole genome shotgun strategy
What was the public effort strategy?
- The human genome was partitioned into large sequences and stored in yeast mini chromosomes
- Each mini chromosome sequenced
- sequences then assembles
What as the technique used by public funded strategy?
Human genome sequencing strategy
An overview of the human genome strategy
- partial digestion of DNA
- large- insert clones are analysed for markers or overlapping restriction sites
- These can then be assembles into a contig (continuous stretch of DNA)
- A subset of overlapping clones that cover the entire chromosome are selected and fractured , these pieces are then cloned.
- Each of these small- insert clones is sequenced and overlap to determine the structure
Why was the human genome sequencing strategy not useful?
Progress was very slow
The second human genome project, used Whole- genome shotgun sequencing
- Genomic DNA is cut into small overlapping fragments and cloned in bacteria
- Each fragment sequenced
- overlap is used to sequence the clones , the entire genomic sequence is assembled by powerful computer programs
What is structural Genomics?
Determines the DNA of sequences of entire genomes
What is the aim of structural genomics?
To understand the organisation and sequence of genetic information contained within a genome
What was the big discovery, in regards to gene number.
estimated that there would be 50,000 to 100,000 genes
Roughly 20-22k genes
What is the difference between nuclear and mitochondrial genomes?
nuclear genome only 1.5% protein coding vs mitochondrial genome is 93% protein coding
What are transposons?
- half our genome is made up of them , no one knows exactly what they do
What is comparative genomics?
Refers to the comparison of genomes to understand evolution of genes and species and the function of genes
What are the aims of comparative genomics?
- To annotate genes and identify conceived and functional areas
- To understand how genomes evolve
- To understand how species relate to each other
- To understand the function of genes
What are homologous genes
Genes that are evolutionarily related through speciation
What are orthologs
Homologous genes in different species that evolved from th same, gene in a common ancestor
What are paralogs
Homologous genes arsing by duplication of a single gene in the same organism
Sequence evolution and functional relevance
Genes can show accelerated rates of evolution or unusually low rates of evolution .
e.g accelerated evolution = myoglobin shows accelerated evolution to increase oxygen capture
Definition of the transcriptome
All the RNA molecules transcribed from a genome
Definition of the proteome
All the proteins encoded by the genome
Transcriptomics; the techniques to understand the gene activity
- Microarrys : nucleic acid hybridisation - using a known DNA fragment as a probe to find a complementary sequence
- Next generation sequencing : Sequencing RNA fragments which are then annoyed by aligning them to a reference genome sequence
What were the expectations from the human genome sequencing project ?
Within 10 years:
- We will understand the function of genes
- We will understand the genomic basis of many diseases including cancer
- We will be able to use this knowledge to diagnose and cure these diseases…
