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Issues with a genetics assignment, the power of bacterial genetics, and explores human genetics through the example of achondroplasia. Topics include mutation rates, mutation jargon, and the role of fathers as the primary source of new gene mutations.
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Biol 322 11/17/09 lecture See announcement on 322 web site Issues with aha3 assignment:
Decoding mutation jargon “The mutations just discussed are single base substitutions. The most striking is achondroplasia, in which 153 of 154 analysed cases are due to a glycine to arginine substitution at codon 1,138. The mutations are in the transmembrane domain of the fibroblast growth factor receptor 3 (FGFR3). Of the 153 mutations, 150 were guanine to adenine transitions and three were guanine to cytosine transversions of the same nucleotide. This means that all the cases of achondroplasia are due to changes in one nucleotide — a nucleotide with the highest known mutation rate (about 10
Cell divisions during oogenesis and spermatogenesis. S, stem cells; G, gonial cells; M, meiotic cells. The total number of cell divisions in the life history of an egg is 24. In males this depends on the number of stem-cell divisions, which is greater in older males.
Everytime a human cell divides it has to replicate 6 X 10 9 base pairs of DNA Every time a base pair is copied, there is a finite probability that an error will be introduced at that site What sorts of errors can be introduced during DNA replication?
rare events The Mutagenesis lab is a great illustration of this principle We will be looking at rare spontaneous and induced mutations: Selection for
s rif r
Screen for Forward mutation lac+ lac - (lac = lactose) Selection for Reverse mutation lac- lac +
GENE MUTATION (change occurs within a gene and is localized to a specific region) ↓ at the DNA level: single base pair substitutions: transitions & transversions indels CNVs = copy number variations other: (i) gene mutation by transposon insertion (ii) expansion of repeated DNA sequences at the level of at the protein gene expression: level: promoter mutations nonsense splicing mutations missense regulatory mutations neutral silent frameshift at the level of gene function: loss-of-function gain-of-function ↑ CHROMOSOME MUTATION CNVs = copy number variations involves segments of chromosomes or whole chromosomes alterations in chromosome structure and number (deletion, duplications, translocations and inversions)
As we collect and analyze data from this experiment consider what types of mutations might produce a lac- from a lac+ strain or might revert the former into the latter? Forward mutation lac+ lac - (lac = lactose) Reverse mutation lac- lac + What can you tell me about the E. coli lac operon?
Weapons of Microbial Drug Resistance Abound in Soil Flora http://fire.biol.wwu.edu/trent/trent/microbialresistance.pdf Acquisition of antibiotic resistance from another cell (+) and adaptive response to selection (A) will be explored in the 1 st and 3 rd bacterial genetics labs.
How might an AR gene or allele confer resistance to an antibiotic?