* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Lecture#10 - Classification of mutations and gene function Readings
Gene therapy wikipedia , lookup
Koinophilia wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Genetic drift wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
Frameshift mutation wikipedia , lookup
Population genetics wikipedia , lookup
Genetic engineering wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
History of genetic engineering wikipedia , lookup
Oncogenomics wikipedia , lookup
Genome editing wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Designer baby wikipedia , lookup
Point mutation wikipedia , lookup
Lecture 10; 2007 Biology 207; Section B2; Good Lecture#10 - Classification of mutations and gene function Readings: Griffiths et al (2000) 8th Edition: Ch. 6 pp192-199 , Ch 16 pp 535-537. 7th Edition: Ch. 15 pp 467-484 Problems: Concepts: How do DNA mutations affect the organism? 1. DNA sequence can be altered and a mutant or variant can result. 2. Multi-cellular organism can have somatic and germline mutations. 3. From the wide variety of mutational possibilities for most genes (alleles), we can usually distinguish only functional and non-functional alleles. 4. The functional allele is usually dominant to the non-functional allele in individuals with both alleles (called a heterozygote). 5. Mendel's results demonstrate the process of segregation. Mutation - change in the DNA sequence can give rise to a phenotype if it modifies a gene: This definition can be a bit vague, in the sense that the phenotype needs to be defined. (eg. A mutation may affect a sequence change that can be detected as an RFLP or single base pair change (SNP = Single Nucleotide Polymorphism), but not affect the protein product). Mutant - an organism bearing a mutant gene that expresses itself in the phenotype of the organism Genes and Alleles Each modified form of a gene is referred to as an allelic form; an allele. Allelic forms: "normal" or wild type sequence or allele - functional - What is wild-type? variant allele - the DNA sequence is different from wild-type - produce a product that is active and functional (yet have bp changes in the gene) -> mutant allele - the DNA sequence is different from wildtype - a change in base pairs leading to a change in gene structure - substitution, deletion or duplication - makes the gene 1) less functional 2) non-functional -> Muller's morphs 3) mis-functional General classification of germline mutants Text -> The mutation's effect on the organism. 1 Lecture 10; 2007 Biology 207; Section B2; Good 1) Morphological mutations - change in the form of the organism - size, shape, color, number, etc. eg. bithorax 2) Lethal mutations - mutation that leads to or causes death of an organism - most commonly recessive lethal - homozygotes die - heterozygotes are viable 3) Conditional mutations - relies on the concept of: Genotype + Environment + Interaction (of G & E) = phenotype - organism expresses mutant phenotype only under specific environmental conditions Under restrictive conditions they express the mutant phenotypic (e.g., high temp.),; while under permissive conditions they show a wild type phenotype 4) Biochemical mutations - produce auxotrophic mutants from prototrophic parents This is really a specific type of the conditional mutation class. e.g. - your lab exercises Different types of mutations that have been used in developing genetic maps. 1) Morphological mutations (eg. eye colour, Drosophila, kernel colour, maize) 2) Electrophoretic enzyme variants (first used in the mid-60’s to look for genetic variation (R. Lewontin) 3) RFLP variants (Molecular markers used for the first time). Detect changes in a restriction enzyme site. 4) Other DNA markers which can detect either Indel’s (Insertion or Deletions), SSR’s (Simple Sequence Repeats; used in human forensics), or SNP’s. Mutations in haploid and diploid organisms Haploids - usually one copy per gene - single cells - expression of gene affects the cell's phenotype directly - e.g. bacteria, haploid yeast Diploids - two copies of each gene - interactions of alleles - often multicellular - different tissues - expression is NOT direct - e.g. diploid yeast, Drosophila and other animals and plants 2 Lecture 10; 2007 Biology 207; Section B2; Good Multi-cellular organisms Somatic vs Germline Cells In multi-cellular organisms the cells are divided into two primary types: Somatic cells - form the tissues of the organism and not used in reproduction - not passed on to the next generation Germline cells - form the germ cells used in reproduction - are passed on to the next generation Particularly important in animals less so in plants where somatic cells become germ tissue. The change, or mutation, occurs in the DNA of a single cell. Somatic vs Germline Mutations Somatic Mutations - occur in cells that populate the body - a mutant cell, and its descendants, will form a clone of cells - population of mutant cells among wild type cells - In humans -> mutation ->cell that is cancerous -> clone of cells -> cancer - only produce an effect (phenotype) in the individual in which they occur -> mosaic - will NOT be passed on to the next generation of organisms Mosaic - an individual composed of two (or more) types (lines) of cells that differ in their genetic composition eg. Transposable elements in corn Germline (germinal) Mutations - occur in the sex cells or cells that lead to sex cells (eggs or sperm) - can be passed on to the next generation of organisms - Animals -> segregate these cells from somatic cells - Plants -> somatic cells can become germ cells; therefore somatic mutations can become germline mutations Diploids have two alleles for each gene locus In a diploid the two alleles for each gene locus sometimes makes it difficult for an observer to ascertain the genotype directly from the phenotype 3 Lecture 10; 2007 Biology 207; Section B2; Good Geneticists use the phenotype to infer genotype or possible genotypes for an individual. Genotype -the genetic constitution of an organism -in a diploid this means the two alleles Phenotype -the observed properties of an organism -produced by the genotype in conjunction with the environment How does one infer genotype from phenotype? Haploids - direct genotype -> phenotype Diploids - directly inferring is not always correct since there are two alleles to be determined Note: The concepts of alleles, dominance, recessiveness, pairs of genes, homozygotes, heterozygotes all come to us from the work of Gregor Mendel and his peas. Example: Gregor Mendel's peas Gregor Mendel did his experiments in the 1860's with the pea plant (Pisum sativum) The pea plant is useful because it can be either: 1) Self-pollinated - pollen fertilizes the ovum in the same individual plant (flower) and one can get gametes of both sorts (pollen and ovum) from the same genotype (individuals) 2) Cross-pollinated -pollen fertilizes the ovum of a different individual plant and one can get gametes of either sort (pollen and ovum) from different genotypes (different) True-breeding strains - a population of individuals that shows no variation for a particular character. Example: Mendel's Round and wrinkled character of the pea Start with two different forms of a gene: two alleles "R" (e.g. wild type) - produces a functional product "r" (e.g. mutant) - no functional product Parents: true breeding Round (RR) cross (x) to wrinkled (rr) P1 Gametes: R r Progeny: Round (Rr) F1 Heterozygotes vs homozygotes Diploid individuals have 3 possible combinations of alleles: RR ---> homozygote - both alleles are R rr ---> homozygote - both alleles are r Rr ---> heterozygote - one of each allele Dominant vs recessive Diploid individuals have 3 possible combinations of alleles: RR ---> homozygote - large R phenotype rr ---> homozygote - small r phenotype Rr ---> heterozygote -phenotype is ???????? 4 Lecture 10; 2007 Biology 207; Section B2; Good In the most common circumstance, Rr has a normal (wild type) phenotype, because the single normally functioning allele, R, provides sufficient function to produce a normal phenotype. Note: Because the "R" allele determines the phenotype in the diploid heterozygote it is considered dominant to the "r" allele. Because the "r" allele is masked by the "R" allele, the "r" allele is considered recessive to the "R" allele. Note: 1). The terms dominant and recessive are always used in relation to another alleles - in a diploid individual 2). Dominance and recessive are not an innate property of an allele but a relative one. Notation - Frequently capital letters are used to denote dominant alleles while the recessive alleles are given the lower case equivalent. Mendelian Genetics Parents: true breeding Round (RR; P1) cross (x) to wrinkled (rr; P2) RR rr R r Rr genotype RR Rr rr ratio 1 2 1 phenotype ratio Round 3 wrinkled gametes F1 progeny R r R RR Rr r Rr rr F2 progeny 1 The wrinkled character reappeared in subsequent generations. It was only "masked" in the F1 generation (as a heterozygote), not lost. Assigned Problems: none 5