Mapping Database and Information Retrieval - Notes | GEN 440, Study notes of Genetics

Download Mapping Database and Information Retrieval - Notes | GEN 440 and more Study notes Genetics in PDF only on Docsity! 1 1/19/2006, 123 Long Hall Lecture 3: Mapping Databases &Information retrieval Please check: http://people.clemson.edu/~cchen/GEN440_640/ I. Mapping Databases From Last lecture: 1. Two components of Genomic Mapping: a. Representational measurement- different maps b. Process of determining where the biological object gene, or disease locus, lies in the genome linking a molecular signature with a biological outcome 2. Major bioinformatics challenge: efficient mining and use of genomic data 3. Relationship between mapping and sequence: sometimes DNA sequence tracts can be thought of ultra high-resolution mapsDNA sequence can be considered as an annotation of the position Today: 4. Types of sequence: (1) Marker-based tags, (2) Gene-based tags, (3) Single gene sequences, (4) Pre-finished (draft) sequences, and (5) Completed continuous sequences tracts 5. Genomic Map Elements: a. DNA markers- genomic landmark; STS (sequence tagged sites) b. Polymorphic Markers: sequence variations; restriction based- RFLP, variable number of tandem repeat units (VNTRs); PCR based- microsatellites = short tandem repeats (STR)= SSLP (simple sequence length polymorphism)= SSRs (simple sequence repeats); PCR-based- SNPs – single sequence polymorphisms- occur in each 100 to 300 bases in human- provbably 1 in 1000 base; homework c. DNA clones; BACs, PACs, and YACs, DNA fingerprinting- restriction digestion, fragment pattern are compared between clones to identify those shared subsets; clones whose insert ends have been determined are referred to as sequence– tagged clones (STCs)—physical mapping Note: PACs are bacteriphage P1 based- have a negative selection against non-recombinants& have an IPTG inducible high copy number origin of replication for large DNA production d. Genomic Annotation- biological information 6. Complexity and pitfalls how to minimize errors a. Using several independent maps b. Using maps integrated with all available genomic information 2 c. Seeking experimental evidence 7. Nomenclature issues 8. Resolution limits for different maps 9. Types of Maps: a. Cytogenetic maps: Giemsa bands- labeld -radioactively or fluorescently interphase FISH & fiber FISH array CGH (comparative genomic hybrydization); resources FISH on Extended Chromatin Fiber Preparation - A higher resolution method for detection of signals is obtained by artificially extending chromatin fibers on a slide glass before DNA hybridization (Figure 1). Fiber FISH Procedure Cells are spread and air-dried on a slide glass. The cells on a slide glass are lysed by detergent (Triton X-100) in a closed container. Chromatin fibers attach to the slide glass when it is slowly removed from the container. The preparation is fixed with ethanol. High resolution FISH at a distance of 5-700 kilobase pairs becomes possible. The probes are hybridized following standard procedures. b. Genetic linkage (GL) maps starting point for many disease-gene mapping projects & back bone for physical mapping; rely on the naturally occurring recombination & polymorphic markers; using genotypes oobserved in multigeneration families; low recombination = linked; use statitiscal models for quatification = lod score – maximum likelihood ; logarithms of the odds;; distance in GL not proportion to physical maps c. Physical Maps: (1) STS content maps; (2) clone alignment; (3) radiation hybrid mapsintermediate resolution between Gl and physical maps; (4) sequence- based maps 10. Genome databases 11. Comparative Maps: synteny and prediction from one species to