Lecture Notes on Polymorphism - Bioinformatics | GEN 440, Study notes of Genetics

Download Lecture Notes on Polymorphism - Bioinformatics | GEN 440 and more Study notes Genetics in PDF only on Docsity! GEN440/640 Bioinformatics 123 Long Hall 1 2/9/2006 Lecture 9: Polymorphism I. Introduction 1. Polymorphism: The occurrence in a population (or among populations) of several phenotypic forms associated with alleles of one gene or homologs of one chromosome 2. Genetic Polymorphism: The occurrence together in the same population of more than one allele or genetic marker at the same locus with the least frequent allele or marker occurring more frequently than can be accounted for by mutation alone. 3. Allele: Alternative form of a gene. One of the different forms of a gene that can exist at a single locus; One of the different forms of a gene or DNA sequence that can exist at a single locus. Alternatively, one of several alternate forms of a gene occupying a particular location on a chromosome. 4. Cause of polymorphism: mutation 5. Allele frequency: Often called gene frequency. A measure of how common an allele is in a population; the proportion of all alleles at one gene locus that are of one specific type in a population. 6. Operational definition: allele frequency > 1%; otherwise called mutations or rare alleles 7. Further distinction: common polymorphism (alleles), vs. private polymorphism less useful for this distinction 8. Why are we interested? Why do we care?Identifying the genes conferring susceptibility or resistance to common human diseases should become increasingly feasible with improved methods for finding DNA sequence variants on a genome-wide scale (Collins et al. 1997) 9. Types of polymorphisms: SNP 1/1000, STR (short tandem repeats); sequencing project = SSLP (simple/single sequence length polymorphism)- human mouse & rat genotyping, SSR simple sequence repeat-plant genome; microsatellite DNA-evolution 10. Satellite DNA: This term was used originally to describe a discrete fraction of DNA visible in a CsCl2 density gradient as a "satellite" to the main DNA band. The term now refers to all simple sequence DNA having a centromeric location, whether distinguishable on density gradients or not. 11. Microsatellites: A very short unit sequence of DNA (2 to 4 bp) that is repeated multiple times in tandem. Microsatellites are highly polymorphic and make ideal markers for linkage analysis. A polymorphism at a microsatellite locus is also referred to as a Simple Sequence Length Polymorphism (SSLP). Alleles are designated by providing the repeat motif and the copy number for each allele. 12 Example of an SSLP marker: GEN440/640 Bioinformatics 123 Long Hall 2 12. Example of an SSLP polymorphism 13. SNP number: >27 million SNPs, > 10 million SNPs validated 14. Example of a TraceArchive. (Figure 7.1) 15. How do you define SNPs ‘human reference genome’ vs. DNAs, 24 initial DNAs for SNPs 16. Coalescent theory to study linkage disequilibrium 17. Ascertainment bias (Fig 7.2) 18. What is a DIP (deletion-insertion polymorphism)? An observed insertion of one or more nucleotides in one individual relative to another individual. Since the molecular event that gave rise to this observation cannot be determined from the observation alone (i.e. was it an insertion or a deletion), both events are incorporated into the name of this polymorphism type. Again who is the wild type! 19. What is a MNP (multiple sequence polymorphism); Variations that are multi-base variations of a single, common length (all alleles same length where length>1); Sample allele: ACG/TTC 20. The structure of submitted SNP components: variant alleles and the flanking nucleotide sequence that specifies a unique position in the genome (Figure 7.6 text, p.179): (10 complete survey; (2) partial; (3) capture from publication, survey (position) unknown