GEN 3022 1st Edition Lecture 35Outline of Last Lecture I. DNA sequencingII. Dideoxy method a. Mechanismb. Dideoxynucleotidesc. Chain terminationd. Automated sequencingIII. Blotting methodsa. DNA librariesb. Southern blottingc. Northern blottingd. Western blotting IV. Biotechnologya. Earlier studiesb. Uses of microorganisms in biotechnologyV. Biological control and bioremediationa. Biological controli. Bacterial species as biological control agentsii. Microorganisms b. BioremediationVI. Geneticall modified animalsa. Purpose of genetically modified animalsi. Livestock ii. Reproductive cloning iii. Stem cellsiv. Cloning of somatic cellsb. Gene additioni. Gene addition in eukaryotesc. Gene replacementi. Mice and gene replacementsii. Gene knockoutiii. Gene knockinVII. Genetically modified plantsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.a. History b. Transgenic plantsi. A. tumefaciensii. Process VIII. Human gene therapya. Researchb. Transfer methodsOutline of Current LectureI. Introductiona. Importance of genetic researchb. Genetic diseasesII. Study of genetic diseasesa. Inheritance Patternsb. Pedigree Analysisc. ObservationsIII. Autosomal Inheritancea. Tay-Sachs Diseaseb. Autosomal Recessive Inheritancec. Huntington Diseased. Autosomal Dominant Inheritancee. Explanations of Dominant DisordersIV. X-linked Inheritancea. X-linked Recessive Inheritanceb. Hemophiliac. X-linked Dominant InheritanceV. Locus Heterogeneitya. Example: HemophiliaVI. Detection of Disease Causing Allelesa. Genetic testing and screeningb. Problems with testing and screeningCurrent LectureI. Introductiona. Importance of genetic research: knowledge of genetics has a profound effect on the way many diseases are diagnosed, treated, and prevented. Research in this field has a great impact on the advancement of medicine. Currently, several hundred genetic tests are in clinical use.b. Genetic diseases: about 12,000 genetic diseases afflict people, and many of theseare the direct result of a mutation in one gene. Genes also play a role in the development of diseases that have a complex pattern of inheritance. II. Study of genetic diseases: provides insights regarding our traits and allows us to find patterns that apply to specific diseases. a. Inheritance Patterns: there are many simple and complicated patterns of inheritance for genetic diseases. Diseases that result from a mutation in a single gene often obey simple Mendelian inheritance patterns. b. Pedigree Analysis: used to determine the pattern of inheritance for a disease using a family tree devised of affected and unaffected individuals. c. Observations: many observations of genetic diseases are consistent with the ideathat a disease is caused, at least in part, by genes. Criteria for a disease to have a genetic basis:i. Criteria 1: an individual exhibits a disease. This disorder is more likely to occur in blood relatives than in the general population.ii. Criteria 2: identical twins (monozygotic twins) share the disease more than fraternal (dizygotic) twins because monozygotic twins were formed from the same egg and sperm (share same genetic information). Geneticists study the concordance of the disorder (degree to which the disease was inherited). iii. Criteria 3: the disease does not spread to individuals sharing similar environmental situations. iv. Criteria 4: different populations tend to have different frequencies of the disease. v. Criteria 5: the disease tends to develop at a specific age range (age of onset). vi. Criteria 6: the human disorder may resemble a genetic disorder that is already known to have a genetic basis in an animal. vii. Criteria 7: correlation is observed between a disease and a mutant humangene or a chromosomal alteration. III. Autosomal Inheritance: non-sex linked inheritance, trait occurs with the same frequency in both sexes. a. Tay-Sachs Disease: inherited in an autosomal recessive patterni. caused by a mutation in the gene that encodes the enzyme hexosaminidase A which is responsible for the breakdown of lipids in the GM2-ganglioside category. These lipids accumulate in the central nervous system.ii. individual appears healthy at birth, but develops neurodegenerative symptoms at 4 to 6 months. Victims die around 3 to 4 years of age. iii. Disease is about 100 times more frequent in Ashkenazi (eastern Europe) Jewish populations. b. Autosomal Recessive Inheritance: an affected offspring usually has two unaffected parents. When two unaffected heterozygotes have children, there is an average of 25% offspring who are affected. Two affected individuals have 100% affected offspring. Diseases that have defective enzymes are typically autosomal recessive, and 50% of the normal enzyme is enough to produce a normal phenotype.c. Huntington Disease: inherited by autosomal dominant pattern.i. Major symptom of the disease is the degeneration of certain types of neurons in the brain which leads to dementia, personality changes, and early death (middle age). ii. Results from a mutation in a gene that encodes a protein termed huntingtin. The mutation adds polyglutamine tract to the protein which causes an aggregation of the protein in neurons.d. Autosomal Dominant Inheritance: an affected individual usually has one or both affected parents and an infected individual with only one affected parent is expected to produce on average 50% affected offspring. Two affected heterozygous individuals will have 25% unaffected offspring. For most dominant disease-carrying alleles, the homozygote is more severely affected with the disorder.e. Explanations of Dominant Disorders:i. Haploinsufficiency: the heterozygote has 50% of the normal protein, which is not sufficient for a normal phenotype.ii. Gain-of-function mutations: mutation changes protein so it gains a new function.iii. Dominant negative mutations: the altered gene product acts antagonistically to the normal product.IV. X-linked Inheritance: where the likelihood of a male inheriting a genetic disease is not always the same as the female.a. X-linked Recessive Inheritance: males have only a single copy of most X-linked genes (hemizygous). A female heterozygous for an X-linked recessive gene will pass the trait on to half of her sons. In this way, males are more likely to exhibit the trait. The mothers of affected males often have brothers or fathers who are affected