Homologous chromosomes fail to separate. Meiosis I: Nondisjunction

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1 Chromosomal Mutations of Number Nondisjunction ( not coming apart ) is when chromosomes do not separate properly during meiosis 1 or 2. The result of nondisjunction during Meiosis 1 is that 2 gametes will receive an extra chromosome, and 2 will be missing a chromosome. The wrong number of chromosomes is known as aneuploidy. If nondisjunction happens during Meiosis 2, only 2 gametes will be effected, 1 will have an extra chromosome and 1 will be missing a chromosome. The result of nondisjunction for individuals created from affected gametes is most often fatal (miscarriage). Those that survive will be aneuploid. Monosomy is missing one homologous chromosome. Trisomy is having one extra homologous chromosome. Many disorders result from nondisjunction depending on which chromosome is affected. Review: There are also chromosomal mutations of structure (missing or additional pieces). These conditions can be diagnosed by karyotyping. Homologous chromosomes fail to separate. Meiosis I: Nondisjunction Result in trisomic zygote Meiosis II Result in monosomic zygote

2 The figure at right is a... Autosomal Mutations of Number...Karyotype This is a female because there are 2 X chromosomes. This individual has Down Syndrome due to nondisjunction of chromosome 21 resulting in trisomy. This disorder is called Down Syndrome because it was first described by John Langdon Down. Female Each person with Down syndrome is an individual intellectual and developmental problems may be mild, moderate or severe. Some people are healthy while others have significant health problems such as serious heart defects.

3 Sex Chromosome Mutations of Number Female Male This is a female because she does not have a Y chromosome. This individual has Turner s Syndrome, caused by nondisjunction and monosomy of the sex chromosomes. This was first described by Dr. Henry Turner. Primary symptoms include being short with puffy hands and feet, organs are affected, along with being sterile (infertile). This is a male due to having a Y chrom. This individual has Klinefelter Syndrome, caused by nondisjunction and trisomy of the sex chromosomes. This was first described by Dr. Harry Klinefelter. Primary symptoms are general feminization and sterility (infertile). There are other such disorders? (CLICK)

4 DNA samples can be obtained from any body tissue or cells through DNA extraction. For example, from cells on a cigarette butt found at a crime scene. Human DNA Analysis Review: Genes are sequences of DNA that code for a polypeptide or protein. Suspect 1 DNA Short Tandem Repeats (STRs) are short sequences of DNA, 2-5 base pairs, that are repeated numerous times (Ex. gatagatagatagata is 4 repeats of "gata". The number of repeats is polymorphic (varies between individuals) and is the basis for DNA fingerprinting. In the DNA samples shown, the genes are the same length but the number of STRs vary. DNA fingerprinting identifies the difference in the number of STRs between individuals. These differences can also be used as markers in genetic testing. Suspect 2 DNA

5 Restriction Enzyme Human DNA Analysis Restriction Site (Where EcoR1 cuts) EcoR1 EcoR1 EcoR1 EcoR1 Suspect 1 DNA EcoR1 EcoR1 EcoR1 EcoR1 Suspect 2 DNA EcoR1 is a restriction enzyme that cuts DNA only where it finds a specific recognition sequence at a restriction site. (Eco for E. coli and R1 for the first restriction enzyme discovered!) In the samples above, the genes fragments are the same length, but the restriction fragments are polymorphic (different lengths). The acronym RFLP stand for Restriction Fragment Length Polymorphism and refers to the difference in length of restriction fragments between individuals. These differences must be analyzed by gel electrophoresis...

6 Gel electrophoresis is a process that separates proteins or DNA fragments according to size and charge. Human DNA Analysis Cathode Sample Well S1 S2 Gel Electrophoresis Agarose gel is a purified form of agar, a porous semisolid derived from algae. Restriction enzyme digested DNA samples are placed in the wells. Because DNA has a negative charge, it migrates toward the anode. Smaller restriction fragments migrate at a faster rate and separate from larger fragments. The gel is then either stained, or radioactive probes are used to visualize the DNA bands. (This is similar to paper chromatography, which separates solutes according to size.) The pattern of bands in each lane is a DNA fingerprint. Larger Fragments Smaller Fragments Anode Suspect 2 committed the crime because the pattern of bands matches the evidence! Evidence Actual Results!

7 Gene Therapy Gene therapy is the replacement of a missing or Cut with restriction enzymes mutated, disease causing gene with a good gene. This corrects the missing or non-functioning protein the gene codes for. The gene therapy in this diagram treats sickle cell anemia. Generally, a vector is anything that carries, transports or delivers something. The vector in this example is a virus that has been genetically engineered to be harmless and deliver the corrective gene. Viruses are thought to be the perfect vector for gene therapy because they only infect specific cells and insert genes into those cells. This diagram shows a virus, genetically engineered to carry the corrective beta- hemoglobin gene, used to infect the patient s bone marrow cells, which are then returned to Viral Vector the patient s where they are expressed, making the proper beta-hemoglobin protein. Bone Marrow Stem Cell Viral Infection & Gene Insertion Return to patient Genetic Engineering

8 Gene Therapy The CRISPR/Cas9 system normally functions as a prokaryotic immune system. It is capable of cutting DNA at very specific sequences that can be programmed. In vivo means inside an organism. Ex vivo means outside an organism. The ex vivo approach is probably safer because unintended cells are less likely to be effected.

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