Looking Within Human Genome King abdulaziz university Dr. Nisreen R Tashkandy GENOMICS ; THE PIG PICTURE

GENOMICS Is concerned with sequencing genomes of all different types of organisms

Shotgun sequences A type of rapid DNA sequencing Make it possible to sequence the entire genomes in a reasonable amount of time

How ? Genomic DNA is cut into large fragments about 150,000,000 base pairs (150MB) long. Insert large fragments into a vector called a bacterial artificial chromosome Clone it into bacteria to replicate Mapping for large fragments to determine their relative order to each other Each large fragment is broken up into smaller fragments then sequence Computer lines up the overlapping sequencies

Human genome The average gene size is about base pairs The number of genes on each chromosome varies from 2,968 genes on chromosome 1 to just 231 genes on the Y chromosome. At least 50% of the human genome consists of small repeating sequences that do not code for sequencing. Genes are randomly clustered together on chromosomes and separated from other clusters of genes by noncoding DNA in between

The areas of DNA that contains genes contain lots of G-C base pairs, whereas the regions of noncoding DNA contain lots of A-T base pairs. Less than 2% of the genome contains the code for proteins and RNA molecules. The other 98% of the genome consists of various types of DNA and DNA whose function isnt yet known.

The known functions of noncoding DNA include: Regulatory sequences that control how DNA is used like promoters and origins of replication. Sequences that are involved in the structuring of DNA within the cell such as those that determine nucleosome positioning Small repeated sequences, Junk DNA, not know function

Comparative genomics The greater the similarities between two genomes the closer the relationship between the species. Database of genomic data are searched for sequences for known genes to see whether the known sequence is found in the genome of another organism Comparison of closely related species such as Chimpanzess and human

Which sequences show the effects of natural selections? Matching up the DNA sequences of related organisms like human and mice Then comparing the rates of mutation in different areas of the genome Secientist then can identify areas of DNA that have undergone natural selection.

Remember All life on earth is very similar. Your DNA sequence shows that close relationship between you and your earthly neighbours. 99% between humans 96% identical to Chimpanzees 40% to mice

Main observations in genome size differences Certain plants have acquired multiple sets of chromosomes during their evolution Organisms that have many sets of chromosomes are Polyploid. Polyploid organisms can have very large genomes. Human have lots of repetitive sequences in their genomes which range from150 to 300 base pair called Alu Alu occurs more than 1.1 million times in human

Functional Genomics The functions of DNA sequences. Relationship between genes and interactions between gene products. (RNAs & proteins)

How much variation within a genome SNPs single nucleotide Polymorphisms we use it to compare or detriment how much variation exists within a genome of a species.

When and where does gene expression occur? By comparing cells of different species or at different developmental stages to each other in order to determine patterns of gene expression between species and during development.

How do genes and the products of different genes interact with each other? Relationships between genes are suggested when the same genes occur in a number of related species Or when genes occur together in the same part of the genome. So gene products are proposed when they are produced at the same time in the cell.

Open reading frames Genes are encoded within open reading frames Sections of DNA that begin with code for a start codon and end with the code for a stop codon. Prokaryotic genes: very easy to locate. Because the sequence of promoters are well known and no introns

Eukaryotic open reading frame Are harder to identify Less than 2% of the human genome is actually made of genes. Contain Introns That’s make it very difficult like looking or hunting for a needle in a haystack

Pharmacogenomics Combines traditional pharmacology and genomics with the goal of TAILORING drug therapies more precisely to suit particular disease or an individual genome

Which genes and proteins are associated with this disease Identify Genes and proteins that cause a particular disease Develop very specific drugs that target those genes and proteins Drugs that very specific will cause far fewer side effect than some of the medicine in use today that effect normal proteins as well as disease causing protiens

What drug is the best treatment for a person with a particular genotype? Adverse reactions to certain drugs. If adverse reactions are common in people with a particular genotype. THEN its possible to use this genotype to predict how they will react to a drug In another words: doctors can start the right treatment from the beginning based on the GENOTYPE

GENOTYOE SCREENING Some disease have a genetic basis While others diseases are more likely to affect some people than others. SO IN SHORT: Allows identification of any genetic diseases that a person inherited Prediction risk factors People can make lifestyle choices to minimize their risk for disease.

References Molecular & Cell Biology for DUMMIES Rene Fester Kratz 2009