Genetics Lecture: Issues with Assignments, Achondroplasia, and Mutation Jargon - Prof. Car, Study notes of Genetics

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:
1. double mutant does not mean homozygous for the
mutant allele:
Homozyous for mutant allele: bb
Double mutant: organism shows two different
mutant phenotypes
2. Prediction of 1:2:1 genotype or 1:2 or 2:1 genotype
frequencies with no indication of the order of
genotype listing:
Assuming no complications to the segregation of a
single gene trait with 2 alleles, the genotype
distribution should be 1:2:1 homozygous wild-
type: heterozyous: homozyous for the mutant allele
Assuming no complications to the segregation of a
single gene trait with 2 alleles, the genotype
distribution should be 1:2:1 +/+: +/-: -/- where +
= wild-type allele and - = recessive allele
3. Needed to indicate that the gametophyte was the
haploid pollen or ovule stage – 1:1 ration results from
inviability of the pollen or the ovule carrying the
mutant allele
4. Carelessness in analyzing the meaning of p value
and how to use it
pf3
pf4
pf5
pf8
pf9
pfa
pfd
pfe
pff
pf12

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Biol 322 11/17/09 lecture See announcement on 322 web site Issues with aha3 assignment:

  1. double mutant does not mean homozygous for the mutant allele :
    • Homozyous for mutant allele: bb
    • Double mutant: organism shows two different mutant phenotypes 2. Prediction of 1:2:1 genotype or 1:2 or 2:1 genotype frequencies with no indication of the order of genotype listing:
    • Assuming no complications to the segregation of a single gene trait with 2 alleles, the genotype distribution should be 1:2:1 homozygous wild- type: heterozyous: homozyous for the mutant allele
    • Assuming no complications to the segregation of a single gene trait with 2 alleles, the genotype distribution should be 1:2:1 +/+: +/-: - /- where + = wild-type allele and - = recessive allele
  2. Needed to indicate that the gametophyte was the haploid pollen or ovule stage – 1:1 ration results from inviability of the pollen or the ovule carrying the mutant allele
  3. Carelessness in analyzing the meaning of p value and how to use it

The types of experiments

that a geneticist can do

are dictated to a great

extent by the model

organism that s/he is

working with

The power of bacterial

genetics is the potential

for studying rare events

  • An estimate of the mutation rate is based upon the accumulated data of newborn studies in four cities.
  • In a total of 242,257 births, seven infants had achondroplasia From these numbers, the rate of mutation of the normal to the achondroplasia allele is calculated to be **_1.4 X 10
  • 5 mutations in the achondroplasia gene per gamete = 1 mutation per 69,216 copies of the gene_** In Spain, Martinez-Frias et al. (1991) found a frequency of achondroplasia of 2.53 per 100,000 live births. _2.53/200,000 gene copies = 1.5 X 10
  • 5_

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

  • 5 per generation). There are mutations at other sites in this gene, but the phenotypes are different.” The achondroplasia mutations are all at a CpG nucleotide pair, known to be a mutation hot-spot. What do you know about CpG islands?

What fundamental difference in the way

human male and female gametes are

produced could explain the fact that

fathers are the primary source of many of

new gene mutations?

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?

The power of bacterial

genetics is the

potential for studying

rare events The Mutagenesis lab is a great illustration of this principle We will be looking at rare spontaneous and induced mutations: Selection for

rif

srif r

(rif = the antibiotic rifamycin)

Screen for Forward mutation lac+lac - (lac = lactose) Selection for Reverse mutation lac-lac +

MUTATION JARGON

GENE MUTATION (change occurs within a gene and is localized to a specific region)at the DNA level:single base pair substitutions: transitions & transversionsindelsCNVs = copy number variationsother: (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-functionCHROMOSOME MUTATIONCNVs = copy number variationsinvolves 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?