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Unformatted text preview: Chapter 11Gene Isolation and Manipulation (10-24-05) Recombinant DNA Technology Problems 12, 13, 21, 25, 26, 31a, b, c Recombinant DNA technology allows us to isolate specific genes from any genome so that we can study their function. Recombinant DNA molecules can be made from any organism by inserting DNA fragments into a cloning vector. (Figure 11-3) Vector Plasmid or Virus Contains an origin of replication for gene amplification. Contains an antibiotic resistance gene or some other gene for selection. Restriction Enzymes Make sequence specific cuts in DNA by cleaving phosphodiester bonds of each strand of the DNA duplex "digestion". (e.g.) EcoRIcohesive "sticky" ends 5'...GAATTC...3' 3'...CTTAAG...5' (e.g.) SmaIblunt ends 5'...CCCGGG...3' 3'...GGGCCC...5' Characteristics of Restriction Sites A. B. 180 axis of symmetry. Usually a 4 (1/256) or 6 nt sequence (1/4096). ...CCC ...GGG + + GGG... CCC... ...G ...CTTAA + AATTC... G... Gene Cloning (Figure 11-5) 1. 2. Digest chromosomal and vector DNA with an enzyme. Mix together. Sticky ends anneal (hybridize, base-pair) due to complementarity. Can also use blunt ends. 3. 4. 5. THEN 1. 2. 3. Determine the DNA sequence and identify the Open Reading Frame (ORF). Engineer mutations to study gene function and gene regulation. Overexpress gene and purify the protein to study function. Seal the phosphodiester bonds "nicks" with DNA Ligase. Transform E. coli and select for drug resistance or by complementation (compensation) of a mutant defect. (Figure 11-6) Amplify and purify recombinant DNA. Animation Vectors A. Plasmids (Figure 11-7) Small, circular, origin of replication, antibiotic resistance gene. Can clone several kb. B. Expression Vectors Specialized plasmids that contain transcription and translation signals to allow overproduction of the protein encoded by the gene. Express eukaryotic genes in bacteria (e.g., human insulin). C. Shuttle Vectors Contain origins of replication for two organisms. (e.g.) E. coli and SV40 (Monkey virus). Clone in E. coli, purify DNA, transfect mammalian cell line. D. Bacterial Artificial Chromosomes (BACs) Based on the F plasmid. ~150 kb can be cloned. E. Yeast Artificial Chromosomes (YACs) Contain an origin of replication, telomeres, and a centromere. ~1000 kb can be cloned. cDNA (complementary DNA) DNA generated from mRNA and reverse transcriptase, thus no introns. DNA Library Random chromosomal or cDNA fragments cloned into one of the above vectors. A random population of clones should contain every gene. Isolate a specific gene by selection (cloning by complementation) or screening. Cloning by complementation 1. 2. Isolate a mutant strain giving the desired phenotype. Transform the mutant strain with a DNA library and directly select for the positive clone by its ability to complement the mutant defect. DNA Probe A radioactive DNA fragment that is complementary to the gene you want to clone. Can be the homologous gene from a related organism. (e.g., clone a human gene using the cloned mouse gene as a probe) Electrophoresis Used to fractionate DNA, RNA or proteins based on their size. (e.g., Digest DNA and run on a gel) (Figure 11-13) Southern Blot Probing for a DNA fragment using a DNA probe. (Figure 11-14) Northern Blot Probing for an RNA fragment using a DNA probe. Western Blot Probe for a protein using antibodies. Restriction Mapping Restriction sites in a DNA fragment can be used to subclone fragments within the fragment. 1. 2. 3. 4. 5. Digest DNA with one of several enzymes. Run digested DNA on an agarose gel to separate fragments. Stain DNA with ethidium bromide (EtBr) which intercalates between bases. View under UV light (EtBr fluoresces). Single, double or partial digests. (Figure 11-16) Sample Problem A linear 13 kb fragment of DNA is digested with various restriction enzymes. The results of single and double digests are shown below. Enzyme(s) BamHI EcoRI HindIII BamHI and EcoRI BamHI and HindIII Fragment Sizes (kb) 3 and 10 6 and 7 1 and 12 3, 4 and 6 1, 3 and 9 What fragment sizes are expected if the 13 kb fragment is digested with EcoRI and HindIII? Chapter 11Gene Isolation and Manipulation (10-28-05) DNA Sequencing Used to determine the nt sequence of any gene. Can resolve DNA fragments differing by 1 nt. (Gilbert and Sanger shared the Nobel Prize) A. Dideoxy Sequencing Dideoxy nts lacking a 3' OH group can't be extended by DNA pol once incorporated. Random incorporation because of a mixture of dNTPs and one ddNTP. (ddATP, ddCTP, ddGTP, ddTTP) (Figures 11-17 and 11-18) B. Automated Sequencing Uses fluorescent dyes (Figure 11-19) Polymerase Chain Reaction (PCR) (Mullis Nobel Prize) Used to amplify specific regions of DNA. Uses a thermostable DNA polymerase. (e.g., Taq) Can amplify DNA from a single cell. (Figure 11-21) Animation Site-Directed Mutagenesis Directing point mutations, insertions or deletions into cloned DNA fragments by PCR. Gene Inactivation 1. 2. 3. 4. 5. (Suicide vector) Clone selectable marker in the middle of a gene. Linearize with restriction enzyme. Transform organism. Double X-over results in replacement of WT gene with disrupted gene. Study the effect of the mutation. Studying Gene Regulation 1. Clone the regulatory region (e.g., promoter) adjacent to a reporter gene (a gene whose protein is easy to assay). Expression of reporter gene depends on cloned regulatory elements. 2. 3. Study regulation. Repeat with deletions or point mutations in regulatory region. Human Genetic Disorders Recessive disorders cause over 500 genetic diseases. Would like to determine if individual carries mutant gene(s). Restriction Fragment Length Polymorphism (RFLP) Sickle cell anemia affects 0.25% of U.S. African-Americans. GAG (HbA)GTG (HbS) mutation eliminates an MstII restriction site. Change detected by Southern blotting. Change in banding pattern diagnostic for sickle allele. GluVal change alters Hb structure (Figure 11-24) DNA FingerprintingUsed in forensic medicine. Variable Number Tandem Repeats (VNTRs) Humans1-5 kb sequences consisting of repeats 15-100 nt long. 1. 2. 3. 4. Digest DNA with restriction enzyme that does not cut within VNTRs. Run DNA on gel. Southern blot with VNTR probe. Pattern on autoradiograph is highly individualistic. DNA samples can be amplified by PCR using trace amounts of blood, semen, hair. Eukaryotic Transgenic Technology E. coli4.6 million bp Human3 billion bp PlantsSome even larger Specialized techniques were developed to handle large genomes (e.g., YACs). Transgenic Technology Methods used to transfect eukaryotic cells. Transgenic Organism Organism that develops from the transfected cell. Transgenic Plants Ti (Tumor Inducing) Plasmidfrom Agrobacterium tumefaciens Causes crown gall (plant tumors). (Figure 11-28) Bacteria infects plant and transfers part of plasmid called T DNA (T=transfer) into plant genome. Clone gene in middle of T DNA so that the gene is inserted into plants with T DNA. (e.g.) Firefly luciferase geneglow in the dark plants. Transgenic Animals Applying similar techniques to study the function of animal genes. Can be used for gene therapy in humans. Human Gene Therapy Correct genetic defects by transferring WT genes into the germ line (gametes) or other actively dividing tissue (e.g., stem cells). SCID (Severe Combined Immunodeficiency Disease) "Boy in the Bubble Disease". No functional immune system. Has been cured in 9 of 11 individuals in a clinical trial with gene therapy (France). One individual developed leukemia due to the point of insertion in the genome. Chapter 12Genomics (10-31-05) Genomics The study of entire genomes. > 250 completed bacterial genomes. Problems (none) Theoretically possible to complete a bacterial genome in a single day using automated technology. (Figure 12-3) Human, Drosophia, yeast, C. elegans, etc also sequenced. 1. Sequence the entire genome A. Shotgun sequencing. (Figure 12-2) Sequence random clones and then assemble the sequence into a complete chromosome by looking for overlaps within the sequenced clones. Requires more sequencing (10 genome equivalents) but no need to order clones. B. Sequence ordered clones. Less sequencing and no need to assemble the genome but it takes time to order the clones. 2. Bioinformatics Annotate the genome (Figure 12-22) A. Identify all of the Open Reading Frames (ORFs) encoded in the genome. 1. Computationally remove introns in higher eukaryotes. 2. Compare to full-length cDNA sequences. 3. Predict regulatory regions "docking sites for regulators." (comparative genomics) 4. BLAST (Basic Local Alignment Search Tool) search. Search public databases for similar DNA and/or protein sequences. A hit suggests that the gene is real. (comparative genomics is a powerful approach-Figures 12-25 and 12-26) 5. Codon bias. Human Genome ~25,000 genes There are about 3 alternative splicing pathways per gene. Thus, the proteome is thought to be about 3 times the size of the genome. (i.e., ~75,000 proteins) 3. Functional Genomics Using genomic approaches to study all of the gene products simultaneously. A. Transcriptome analysis Analyze the expression patterns of all genes simultaneously under various growth conditions, times during development, when a regulatory protein is mutated, etc. Microarray studies (i.e., gene chips) (Figure 12-27) Animation B. Proteome analysis Using 2-D gels and mass spectroscopy to identify changes in protein levels under various growth conditions, times during development, when a regulatory protein is mutated, etc. Complementary to transcriptome analysis but also identified translationally controlled genes. C. Interactome analysis Identification of the complete set of physical interactions between proteins and DNA, proteins and RNA, and between proteins. Yeast 2-hybrid assay (Figure 12-29) D. Phenome analysis Identification of all phenotypes associated with the inactivation of each gene. Chapter 13Transposable Elements (11-2-05) Transposable Genetic Elements Problems 2, 3, 6, 7 "Jumping Genes" Genetic elements than can move or "transpose" from one position to another. Barbara McClintock won the Nobel Prize (1983) for her pioneering work (1940s) on Maize. Ac/Ds elements. Transposable elements are present in essentially all organisms. Bacteria 1. Insertion Sequences (IS) 2. Transposons (Tn) When IS elements insert in the middle of a gene it inactivates that gene. (e.g.) IS1, IS2, IS3, etc... tnp IR IR IR--->Inverted Repeats tnp encodes transposase, the enzyme responsible for transposition. IS elements are sites where crossing over (X-over) can occur. F (fertility factor) integration into the chromosome to generate Hfr strains occurs via X-overs between IS elements in the F plasmid and chromosomal IS elements. (Figure 13-8) Transposons Composite elements that contain tnp and additional genes (typically a drug resistance gene). A. Composite Transposon (Figure 13-9a) Composed of 2 IS elements and a drug resistance gene between them. (e.g., Tn10 contains 2 IS10 elements and a tetracycline resistance gene) Transposase comes from one of the IS elements and the IS elements also function as the IRs. B. Simple Transposon (Figure 13-9b) Composed of a transposase gene and typically a drug resistance gene. IRs similer to those for IS elements. Mechanism of Transposition Transposition involves cleavage of the DNA target followed by insertion of the transposable element. Subsequent filling in of the resulting single-stranded gaps generates target site duplications. (Characteristic of transposable elements) Transposase is responsible for target site selection and DNA cleavage. A. Replicative One copy of the transposable element remains in the original site and a second copy inserts into a new site. Requires DNA replication. B. Conservative (non-replicative) No DNA replication. The transposable element is excised and moved to a new site. Disrupted genes at the original site revert to wild-type. (Figure 13-11) Multiple Antibiotic Resistance Transposons can jump from a naturally occurring plasmid to a chromosome or from plasmid to plasmid. The plasmids can move from bacteria to bacteria via transformation and/or conjugation. Can lead to multiple antibiotic resistant strains of bacteria. (Huge problem in a clinical setting) (Figure 13-10) Eukaryotic Transposable Elements Can inactivate a gene, cause chromosome breaks, and transpose to new locations (replicative or nonreplicative). A. Class IRetro-transposons (RNA elements) Must be transcribed into RNA, then reverse transcribed to DNA, then inserted. Class I elements can't excise and restore function to an interrupted gene. (e.g., yeast Ty, Drosophila copia, human Alu elements) These elements are similar to retroviruses (both have gag and pol genes). gaginvolved in RNA maturation polreverse transcriptase The absence of the env (envelope) gene prevents packaging of the genome into a vial particle. Instead, the DNA is inserted into a new place in the genome. (Figure 13-15) RetrovirusesssRNA animal viruses. (e.g., HIV) 1. 2. Eject RNA genome. Reverse transcriptase synthesizes dsDNA from the ssRNA. A. First DNA strand synthesized using RNA as template. B. Second DNA strand synthesized using the first DNA strand as template while simultaneously degrading the RNA strand. 3. Integration into the mammalian genome. B. Class IIDNA transposons Similar to bacterial transposable elements (encode transposase). (e.g., Maize Ac and Drosophila P elements) Maize Ds elements are defective Ac elements (no functional transposase). Requires transposase from Ac to transpose. (Figure 13-19) Excision from a gene can lead to reversion to wild-type. (Figures 13-5 and 13-6) Autonomous Elements Fully functional (can transpose by themselves). (e.g., Ac elements of Maize) Non-autonomous elements Requires an autonomous element to supply transposase for transposition. (e.g., Ds elements of Maize) Humans Transposable elements can be VERY abundant in genomes. ~ 50% of the human genome is derived from transposable elements. >1 million Alu sequences alone. There is 20 times more human DNA corresponding to transposable elements than protein coding DNA. LINEs (autonomous) and SINEs (nonautonomous) are retro-transposons. Alu is a SINE. The majority of transposable elements are inserted in introns or between genes. Natural selection reduces exon insertions being fixed in the population. Chapter 14Gene Mutation (11-4-05) Gene Mutation Problems 2, 17, 21, 24 A mutation in a specific gene resulting in a new allele. Wild type (WT) compared to a mutant or variant. Mutant An individual or strain carrying a mutation. Mutagen Agents that increase the rate of mutations. Forward Mutation Any change from the WT allele. Reverse Mutation Change to the WT allele (true reversion). Second Site Suppressor A change in the same gene or a second gene resulting in a complete or partial phenotypic reversion to WT (second site reversion). Loss of Function Mutation Results in the loss of activity. Gain of Function Mutation Results in a new or altered activity. Transition Substitution of a pyrimidine for the other pyrimidine OR a purine for the other purine. Transversion Substitution of a pyrimidine for a purine and vice versa. Point Mutations (A-E) Single nucleotide changes. A. Silent (Synonymous) Substitution The mutation changes one codon for an amino acid into another codon for the same amino acid. B. Missense Mutation The codon for one amino acid is replaced by a codon for another amino acid. C. Nonsense Mutation The codon for an amino acid AA is replaced by a stop codon. D. Deletion Removal of one nucleotide. E. Insertion Addition of one nucleotide. D and E will lead cause frameshifts if in a protein coding region. (Table 14-2) I. INDUCED MUTATIONS Produced when a cell or organism is exposed to a mutagen. (e.g., chemicals or UV light) A. Base Replacement Molecules that are similar in structure to bases (base analogs) but have different pairing properties can replace the normal base in the DNA during replication. B. Base Alteration (Figure 14-9) Mutagens that alter the structure of a base lead to mispairing. (e.g. alkylating agents) C. Base Damage (Figure 14-12) Damage so severe that pairing can't take place. Will lead to a replication block (lethal if not repaired). (e.g., UV-induced cyclobutane pyrimidine dimmers OR 6-4 photoproduct) II. SPONTANEOUS LESIONS Occur in all cells without a mutagen. A. Depurination When the N-glycosidic bond between the base and the sugar is broken. (Put in part of Figure 14-14) The resulting apurinic site (AP site) can't specify a complementary base during replication. B. Deamination Loss of an amino group from the base. Deamination of dC yields dU. dU pairs with dA. (Figure 14-18) C. Errors in DNA Replication 1. Keto-Enol Shift Normally A, C, G, and T are in the keto form. (Figure 14-5) Errors occur during DNA replication when rare imino forms of A and C or rare enol forms of T and G are incorporated by DNA polymerase. These tautomers pair with the wrong base. (Figure 14-6) The DNA pol III editing function removes mismatches when the rare forms change back unless polymerization has already moved past the mismatch. (DNA Repair required) 2. Replication Slippage (DNA repair required) Results in deletions or insertions that can cause frameshifts. (Figure 14-21) Animation Triplet repeat expansion diseases in humans is thought to occur via replication slippage. (e.g., Fragile X syndrome, Huntington;s disease, myotonic dystrophy) D. Oxidative Damage Byproducts of aerobic metabolism produce compounds that cause oxidative DNA damage. (e.g., superoxide radicals and hydrogen peroxide H2O2) Chapter 14DNA Repair (11-7-05) Several enzymatic systems exist to repair various types of DNA damage. In humans several disorders are caused by defects in DNA repair systems that can lead to cancer. Classes of Repair Pathways (Systems) I. Prevention of Errors Before they Happen Some enzymes neutralize damaging compounds. (e.g., Detoxification of molecules that cause oxidative damage). Superoxide dismutase converts oxygen radicals to hydrogen peroxide. Then catalase converts hydrogen peroxide to water. II. Direct Reversal of DNA Damage A. Cyclobutane pyrimidine dimers are repaired by photolyase. Requires visible light for the enzyme to work. (Figure 14-26)) B. Removal of alkyl groups added to bases Alkyltransferases responsible for direct reversal. (e.g.,. Methyltransferase of E. coli) III. Excision-Repair Pathways A. Nucleotide Excision Repair (General Excision Repair) Removal of damaged bases, along with several neighboring bases, and then repairing the gap by DNA synthesis. (e.g., cyclobutane pyrimidine dimers, large base aducts) (Figure 14-28) E. coliAn excinuclease (excision nuclease)cuts on both sides of the damaged base removing ssDNA containing the damaged base(s). Gap filled in by DNA pol I. DNA ligase seals the nick. Animation B. AP Endonuclease Repair Pathway AP endonuclease removes AP site by breaking a phosphodiester bonds at the AP site. Then the general excision repair pathway takes over. (Figure 14-27) C. DNA Glycosylase Repair Pathway DNA glycosylases recognize certain damaged bases and cleave the N-glycosidic bond between the base and the sugar leaving an AP site. (e.g., Uracil DNA Glycosylase) The resulting AP site is cleaved by AP endonuclease. Then the general excision repair pathway takes over. (Figure 14-27) IV. Postreplication Repair A. Mismatch Repair (Figure 14-30) DNA editing by DNA pol III did not occur. 1) 2) 3) 4) Recognition of the mismatch. Determine which mismatched base is incorrect. Excise the incorrect base. General excision repair takes over. (Crucial step) Adenine methylase methylates A residues following replication in the sequence: 5' GATC 3' Since it takes a few minutes for the newly synthesized strand to be methylated, the old methylated strand is distinguished from the newly synthesized unmethylated strand. An enzyme introduces a cleavage in the backbone of the unmethylated strand near the mismatch and adjacent to the nearest GATC sequence. ssDNA gap is filled in by DNA pol I. Ligase seals the nick. Chapter 15 Changes in Chromosome Number (11-9-05) (Problems 2, 3, 9, 15, 16, 23, 32, 36a, b) Haploid Cells (n)Cells with one chromosome set (e.g., gametes). Diploid Cells (2n)Cells with two chromosome set (e.g., somatic cells). Monoploid Number (n)Number of chromosomes in the basic set of an organism. EuploidOrganisms with multiples of the monoploid number. PolyploidEuploid with more than two sets of chromosomes. Monoploid = 1n; Diploid = 2n; Triploid = 3n; etc... Monoploid organismsmale bees, wasps, ants. Males develop parthogenetically from unfertilized eggs. These organisms produce gametes via mitosis. Plant Engineering Generate a monoploid plant from a diploid. (Figure 15-11) Then generate a drug resistant diploid from the monoploid plant. Colchicine inhibits mitotic spindle formation. After mutant selection and growth, use colchicine for one cell division. AutopolyploidsMultiple chromosome sets from within one species. Allopolyploids Multiple chromosome sets from closely related species. (e.g., cotton, wheat) Triploids (3x)Problems during meiotic segregation (sterile). (4x) Tetraploid X (3x) Triploid (e.g., Seedless watermelons and bananas.) AutotetraploidsArise spontaneously from accidental doubling (2X to 4X) or use colchicine. Advantages: larger plant and fruit (Figure 15-6) (2x) Diploid Polyploidy in animals Leeches, brine shrimp, flatworms Common in amphibians and reptiles. Salmon and trout originated through polyploidy. Oysters (3n)No spawningpalatable all year. Most human triploids die in utero. If born, none survive. Aneuploidy An individual whose chromosome number differs from WT by part of a chromosome set. (Usually one chromosome) Caused by nondisjunction during meiosis (Figure 15-13). If an (n-1) gamete is involved in fertilization, the resulting zygote will be monosomic for that particular chromosome (2n-1). If an (n+1) gamete is involved in fertilization, the resulting zygote will be trisomic for that particular chromosome (2n+1). Animation Monosomics (2n-1) (Deleterious) Missing chromosome disturbs homeostasis. The individual is hemizygous for that chromosome. Deleterious because recessive alleles are expressed phenotypically. Chapter 15Chromosome Mutation (11-11-05) Human Aneuploidy ~10% of all human conceptions have a major chromosome abnormality. Most are spontaneously aborted. A. Monosomic 1. Turner Syndrome (1/5000 females) 44 autosomes with 1X chromosome. Sterile, normal intelligence. ALL MONOSOMICS FOR AUTOSOMES DIE IN UTERO. B. Trisomic 1. Klinefelter Syndrome XXY Lanky builds, retarded, sterile 2. Mean Man Syndrome? XYY Fertile. Aggressive behavior? 3. XXX Phenotypically normal female. Fertile. 4. Patau Syndrome Trisomy 13 Severe physical and mental abnormalities (~ 3 month survival). 5. Edward Syndrome Trisomy 18 Severe physical and mental abnormalities (survive a few weeks). (1/1000 males) (1/1000 males) 6. Down Syndrome Trisomy 21 (1.5/1000 births) Most common human aneuploid. This more common than the translocation form. No family history. Older mothers at greater risk. (Figure 15-18) Mental retardation. Males infertile. Females may be fertile producing normal and trisomic children. Acute Myeloid Leukemia 47/58 patients were aneuploid for either chromosome 8, 9, or 21. Chromosomal Rearrangements A. DeletionsLoss of a chromosomal region. Usually fatal if homozygous. Often fatal if heterozygous. Some small deletions are viable as a heterozygote. Deletions can never revert to WT. Visualized as a deletion loop during meiosis. (Figure 15-28) Pseudodominance Deletion will "uncover" recessive alleles, thus the recessive phenotype is expressed. Small deletions can be mapped due to pseudodominance. Humans Usually caused by a new germinal mutation in one parent. (e.g., cri du chat syndrome. Tip of chromosome 5 deleted). (Figure 15-30) B. DuplicationsGain of a chromosomal region. Can be adjacent to each other or the second copy may be in a novel location in the genome. 3 copies/cell in a diploid. Usually difficult to detect phenotypically. A loop structure may be detected during meiosis. Homologous Chromosomes Tandem Duplication Reverse Duplication A A B B C C B C C B D D Human homozygous duplications have never been detected (probably lethal). Chapter 15Chromosome Mutation (11-14-05) C. InversionsChromosomal region rotated 180. ~ 2% of humans carry inversions. No net change of genetic material. Viable without phenotypic abnormalities unless breakage occurs in an essential gene. Then they are lethal if homozygous. Paired homologs form an inversion loop during meiosis if heterozygous (Figure 15-21b). Paracentric InversionCentromere outside of the inversion. (e.g.) A BC D E F--->A BC E D F X-overs between a paracentric inversion and a WT chromosome result in a dicentric and an acentric chromosome. (Figure 15-22) Acentric fragment is lost. Dicentric breaks randomly in bridge. Animation Pericentric InversionInversion spans the centromere. (e.g.) ABCDE--->ACBDE X-overs between a pericentric inversion and a WT chromosome result in products with a deletion and a duplication of different parts of the chromosome. Animation Inviable deletion products and inhibition of pairing in the inverted region reduces the number of X-over recombinants among the progeny of inversion heterozygotes. Diagnostic features of inversions 1. 2. 3. Decreased recombinant frequency. Inversion loops. Inverted arrangements of chromosomal landmarks. (e.g.) Centromere position (Figure 15-23) Normal 4:1 ratio Inversion 1:1 ratio D. TranslocationsExchange of parts of non-homologous chromosomes. Viable unless the breakpoint is in an essential gene. Reciprocal Translocation A region from one chromosome is exchanged with a region from another nonhomologous chromosome so that two translocation products are generated simultaneously (most common). (Figure 17-23) Animation Diagnostic features of translocations 1. Establishes new linkage groups. (i.e.) gene is now on a different chromosome 2. May alter the size of chromosomes and centromere position. Human Translocations Always in heterozygous state. Cri du chat syndromeMissing the tip of chromosome 5 due to translocation. Down syndromeTwo normal chromosomes 21s, and an additional region of 21 due to translocation. Results in high occurrence in family tree. Philadelphia ChromosomePart of chromosome 22 is translocated to chromosome 9. Often found in individuals with chronic myeloid leukemia. Position Effect Variegation When a gene is translocated to a region near heterochromatin of another chromosome. In some cells the heterochromatin will engulf the gene shutting off expression leading to mutant phenotype. (Figure 15-27) ...
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This note was uploaded on 07/23/2008 for the course BIOL 222 taught by Professor Babitzke,paullee during the Fall '07 term at Pennsylvania State University, University Park.

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