genomics and system biology
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This document discusses various topics related to genomics and systems biology, including DNA sequencing methods, finding and identifying genes, genetic mapping, genome sequencing, the human genome, single nucleotide polymorphisms (SNPs), bioinformatics, systems biology, and applications of genomics such as functional genomics, comparative genomics, metagenomics, toxicogenomics, and epigenetics. DNA sequencing methods determine the order of nucleotides, genes can be located using sequence tagged sites and expressed sequence tagged sites, and genetic mapping aims to locate genes on chromosomes.
genomics and system biology
- 1. Genomics and Systems Biology Dr. Nawfal Hussein Email: [email protected] 1
- 2. DNA Sequencing 2 DNA sequencing, process by which the precise order of nucleotides in a piece of DNA can be determined Sequencing Methods The chain termination method (Sanger dideoxy (enzymatic) sequencing) in which the sequence of a single-stranded DNA molecule is determined by enzymatic synthesis of complementary polynucleotide chains, these chains terminating at specific nucleotide positions The chemical degradation method (Maxam-Gilbert method), in which the sequence of a double-stranded DNA molecule is determined by treatment with chemicals that cut the molecule at specific nucleotide positions. Cleaves DNA template at different nucleotide positions, G, A+G, T+C and C and labels these cleaved fragments.Read A and T by interpreting double bands also including G (with A) and C (with T) .Not used very much historically
- 3. Finding and Identifying Genes 3 Sequence tagged sites (STSs) and expressed sequence tagged sites (ESTs) are unique regions of DNA sequence that are used in mapping the human genome, and other large genomes. STSs and ESTs are mapped relative to each other using linkage analysis on yeast artificial chromosomes (YAC) clones or in radiation hybrid cells. STSs are 100–500 bp unique sequences located in non- repetitive regions of the genome. These sequences can be amplified by PCR. An EST is a type of STS, but is located within genome regions that are expressed into RNA. ESTs are shorter and many may be located in the same expressed region. ESTs can be assayed by generating cDNA using an oligo(dT) primer that binds to the 3´ poly(A) tail, and elongation by reverse transcriptase.
- 4. Genetic mapping ♠ Genetic mapping aims to locate genes to a specific locus or position on a chromosome. Mapping genomes requires more than RFLPs and VNTRs as these are not specific enough. Instead, for mapping something large like the human genome, sequence tagged sites (STSs) and expressed sequence tagged sites (ESTs) are used due to their relative uniqueness. 4
- 5. Genome sequencing 5 The shotgun approach, in which the genome is randomly broken into short fragments. The resulting sequences are examined for overlaps and these are used to build up the contiguous genome sequence. The clone contig approach, which involves a pre-sequencing phase during which a series of overlapping clones is identified. This contiguous series is called a contig. Each piece of cloned DNA is then sequenced, and this sequence placed at its appropriate position on the contig map in order to gradually build up the overlapping genome sequence. A complementary, approach to sequencing the genome is to identify mRNAs. Expressed mRNAs are much less complex than genomic DNA
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- 7. Human genome 7 Human genome contains 3.2 * 109 base pairs. A majority of the base pairs are from euchromatin areas, which contain more relaxed DNA, and thus are easier to access. The remaining sequence is in heterochromatin regions that are condensed. 1.5% of the total genome is estimated to code for protein The actual number of human genes is predicted to fall between 20,000 and 25,000, some of which produce non-coding RNA such as rRNA, tRNA, snRNA, and snoRNA. snoRNAs: Small nucleolar RNAs modify ribosomal RNAs snRNAs: Small nuclear RNAs are part of the spliceosome, that helps to produce mRNA by removing introns of genes and piecing together the exons to be translated into proteins. About half of human genome is non-coding repetitive sequences such as tandem repeats, SINEs, LINEs, and defunct retroviruses and transposons.
- 8. Human genome 8 Between the genome of one individual to the next are variations or polymorphisms such as different bases, insertions, and/or deletions. A single nucleotide polymorphism (SNP) is a single base change. A simple sequence length polymorphism (SSLP) is any insertion and/or deletion different between two individuals. Copy number variations (CNVs) are variations in the number of tandem repeats. SNP analysis is used to screen for hereditary defects and test individuals for phenotypic variations in response to pharmaceuticals. The non-coding parts of the human genome were originally called “junk,” but further analysis has indicated that these are a major source of human genomic variation that perhaps can cause some diseases.
- 9. SNP analysis 9 SNP analysis is useful to identify different alleles for a specific gene, particularly the cytochrome P450 gene, which is used to degrade different pharmaceutical drugs. Individuals do not always react the same to certain clinical drugs, most likely due to natural variations in DNA sequences. Pharmacogenomics is a new field that focuses on an individual’s predisposition (based upon the genomic data) to respond to certain pharmaceuticals. An analysis of SNP is useful to find patterns associated with specific reactions to the drugs.
- 10. Bioinformatics and Systems Biology 10 Bioinformatics uses computers to analyze the large amounts of genetic sequence data. Data mining filters or sifts the data, whereas genome mining specifically applies to identifying the genomic sequence data of interest, cleaning the data of unnecessary information, reformatting the data into convenient forms for analysis, and then interpreting the genomic data for different patterns or relationships.
- 11. Systems biology 11 Systems biology studies how a particular organism adapts its entire genetic expression patterns in response to a different condition. Systems biology compiles information from many different sources to provide an overview of how an organism functions, as a whole. Looking at the big picture provides a valuable assessment of exactly what is occurring because the sum of the parts (meaning the research into individual genes) does not necessarily equal the whole. Often, one condition or environmental difference completely alters the expression profile of genes.
- 12. Applications of Genomics 12 Functional genomic attempt to relate the genome to functional changes in an organism. defining the genes present in the genome. What genes they code for, what regulates their expression, and how this expression varies among tissues, environments/ disease, or individuals. Comparative genomics, the use of other genomes from diverse species, to understanding genomes. Evolutionary comparisons among genomes are used to better annotate genes (providing information on function), define genomic architecture and roles of genes, and develop insights into the creation of novel structures. fish genomic sequences were used to identify many human genes, and these were used as one of the primary pieces of evidence that the vertebrate genome had 30,000 – 40,000 genes and not 70,000 – 140,000
- 13. Applications of Genomics 13 Metagenomics is the study of genomes from multiple organisms that inhabit a particular environment. Toxicogenomics is the study of the complex interaction between an organism ’ s genome and chemicals in the environment, and disease. Epigenetics refers to modifications in DNA that do not involve changes in sequence. These types of changes include methylation patterns, histone modification patterns, and inactivation of certain genes or chromosomes by converting the area into heterochromatin.
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