Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley http://www.allvoices.com/contributed-news/5471722-cancer-zapped-with-nanoparticles-in-humans Chapter 11 Control of Gene Expression and Genome Architecture pg. 205 (RNA interference) through pg. 209 Proteins Outnumber Genes 1.5% of human genome encodes protein 25,000 genes specify up to 200,000 proteins How is this possible? 1. Alternative Splicing within a Gene F 2. Introns as coding sequences DPP and DSP Figure 11.13b 3. ?Cut? 2 proteins from 1 mRNA encoding a precursor Dentin proteins important in tooth formation Dentinogenesis imperfecta Caused by deficiency in proteins DPP and DSP Both are cut from same larger protein Figure 11.13a Majority of Human Genome Does not Encode Protein Rest of genome encodes for Viral DNA Noncoding RNAs Introns Promoters Repeats ? transposons, telomeres, centromeres, pseudogenes, others Table 11.4 Figure 11.10 RNA Interference (RNAi) si RNA (small interfering RNA) Transcribed from opposite strand of specific genes (8%) Complement of the mRNAs, targeting them for removal Acts in the cytoplasm (RISC) Biotechnology ? gene ?knock-down? Chapter 12 Gene Mutation Mutation A change in the nucleotide sequence of a gene (< 1%) Different from a SNP (>1%) Mutations are important to evolution Somatic Mutations Occur in cells of the body, excluding the germline Affects subsequent somatic cell descendants Not transmitted to offspring Germline Mutations Mutations that occur in the germline cells Possibility of transmission to offspring Effect of Mutations Vary Mutations Can Alter Proteins Protective: mutation in CCR5 prevents HIV from binding to immune cell Cause disease: Beta globin gene: sickle cell anemia, Beta thalassemia Sickle Cell Anemia Mutation encodes valine in place of glutamic acid Phenotype associated with homozygotes Altered surface of hemoglobin allows molecules to link in low oxygen conditions Creates sickle shape of RBC Sickling causes anemia, joint pain, and organ damage when RBC become lodged in small blood vessels Sickle Cell Disease Results from a Base Change in Beta Globin Gene Figure 12.2 Thalessemia Caused by another beta hemoglobin mutation Too few beta hemoglobin molecules Excess of alpha hemoglobin leads to iron release, which destroys RBC, damages heart, liver, and endocrine glands. Thalassemia minor (heterozygous) Thalassemia major (homozygous for mutation and more severe) Mutations Cause Disease The same symptoms may be caused by different mutations (multiple alleles) Understanding the molecular cause of a disease may assist in treatment Mutations Change in the DNA May occur spontaneously or by exposure to a radiation or chemicals An agent that causes a mutation is a mutagen Spontaneous Mutation De novo or new mutations Not caused by exposure to known mutagen Errors in DNA replication DNA bases have slight chemical instability Exist in alternating forms called tautomers As replication fork encounters unstable tautomers, mispairing can occur Spontaneous Mutation Figure 12.6 Spontaneous Mutation Rate Rate differs for different genes Vary by size Sequence dependence Hot spots On average, each gene has a 1/100,000 chance of mutating Spontaneous Mutation Rate Only observe phenotypes of dominant mutations Each individual has multiple new mutations Mutational Hot Spots Short repetitive sequences Pairing of repeats may interfere with replication or repair enzymes Palindromes Often associated with insertions or deletions Duplications of larger regions Mispairing during meiosis DNA Symmetry May Increase Mutation Rate Gene Duplication May Increase Mispairing Figure 12.8 Alpha thalassemia Induced Mutations Caused by mutagens, many are also carcinogens and cause cancer Examples: Alkylating agents: remove a base Acridine dyes: add or remove base Xrays: break chromosomes delete a few nucleotides UV radiation: creates thymidine dimers Site-directed mutagenesis: tool for researchers Ames Test An in vitro test of the mutagenicity of a substance One version uses Salmonella bacteria with mutation in gene for histidine Bacteria are exposed to test substance Growth on media without histidine is recorded Bacteria only grow if mutations have occurred Substance can be mixed with mammalian liver tissue prior to testing to mimic toxin processing in humans Exposure to Mutagens Workplace Industrial accidents Chernobyl Medical treatments Weapons Natural sources Sources of Radiation Exposure Table 12.5
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