GEN 3022 1st Edition Lecture 35 Outline of Last Lecture I DNA sequencing II Dideoxy method a Mechanism b Dideoxynucleotides c Chain termination d Automated sequencing III Blotting methods a DNA libraries b Southern blotting c Northern blotting d Western blotting IV Biotechnology a Earlier studies b Uses of microorganisms in biotechnology V Biological control and bioremediation a Biological control i Bacterial species as biological control agents ii Microorganisms b Bioremediation VI Geneticall modified animals a Purpose of genetically modified animals i Livestock ii Reproductive cloning iii Stem cells iv Cloning of somatic cells b Gene addition i Gene addition in eukaryotes c Gene replacement i Mice and gene replacements ii Gene knockout iii Gene knockin VII Genetically modified plants These 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 plants i A tumefaciens ii Process VIII Human gene therapy a Research b Transfer methods Outline of Current Lecture I Introduction a Importance of genetic research b Genetic diseases II Study of genetic diseases a Inheritance Patterns b Pedigree Analysis c Observations III Autosomal Inheritance a Tay Sachs Disease b Autosomal Recessive Inheritance c Huntington Disease d Autosomal Dominant Inheritance e Explanations of Dominant Disorders IV X linked Inheritance a X linked Recessive Inheritance b Hemophilia c X linked Dominant Inheritance V Locus Heterogeneity a Example Hemophilia VI Detection of Disease Causing Alleles a Genetic testing and screening b Problems with testing and screening Current Lecture I Introduction a 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 II III b Genetic diseases about 12 000 genetic diseases afflict people and many of these are 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 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 idea that 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 human gene or a chromosomal alteration Autosomal Inheritance non sex linked inheritance trait occurs with the same frequency in both sexes a Tay Sachs Disease inherited in an autosomal recessive pattern i 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 IV 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 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 with the same trait The daughters of affected males will produce on average 50 affected sons V VI b Hemophilia caused by a defect in an X linked gene