10/26 Genetics Flashcards
allow us to determin the disance between two loci
crossovers
analysis used to find the locations of disease cuasing genes
linkage analysis
the nonrandom association of alleles at linked loci
linkage disequilibrium
what does it mean that tow alleles are linked?
they are on the same chromosome and close to each other on that chromosome, and therefore they are usually inherited together.
what does it mean to be unlinked but syntenic?
genes are on the same chromosome but they are far away on that chromosome and so they are not always inherited together.
what is the purpose of linkage analysis
to figure out which parent the chromosome and the disease causing allele came from.
what is saought in linkage analysis?
we seek markers that are closely linked to a disease-causing mutation
the DNA sequence found on one member of the chromosome pair
haplotype
how can we create unique haplotype from the haplotypes of the parents?
crossover can switch out sections of the haplotype of the parents to give unique combinations and a new haploytype.
how can the realative location of an allele with another affect the rate of recombination?
alleles that are close to each other on the chromsome are less likely to experience recombination.
job syndrome
severe eczema, recurrent skin and lung infections high serum IgE, absent T cell development, cuased by dominant negative STAT3 mutation.
how could you use linkage analysis to determine that a disease causing mutation is on the same chromosome as a given marker?
see the inheritence of the marker following the occurence of the disease.
how can we find how close the disease causing mutation is to a marker on the chromose?
look at the recombination rate (rate at which a child has the marker but not the disease) and then the recombination rate is equal to the centiMorgans (% of recombination) and 1cM is about 1 megabase (Mb) of DNA
How to determine the recombination rate for an autosomal dominant disease locus?
look at the occurance of the disease in two generations and associate it with a specific marker (1,2,3 etc) and then see in the subsequent generation how often that marker allele occurs without the disease or the disease occurs without the marker. each of these would rep. a recombination and these then rep. the rate of recombination out of the total number of offspring
calculated for each possible recombination frequency and tells which recombination frequency is most likely to be the true one.
Log of the odds of linkage vs. no linkage (LOD)
what is the equation for LOD
LOD = log [ p(@=x)/P(@=.5)] where @ is the recombination frequency and p is the probability of a given recombination frequency and x is between 0 and .5
how to inturpret the LOD
LOD > 3 is significant evidence of linkage (1,000 to 1 odds in favor of linkage or the numerator is 1000 times larger than the denominator in the LOD equaiton) while LOD
the probability that a crossover occurs between two loci during meiosis. or a measure of the distance between two loci.
recombination frequency.
how to interpret a LOD vs. recombination frequency graph?
the highest LOD corresponds to the most likely rate of recombination for this set of two loci
what would a recombination rate of zero be?
then most likely there is no recombination…?
how can you compare multiple families with a given disease? to get a significant location of the locci?
can combine LOD scores and recombination rates to get a total and sig. LOD
what is linkage disequilibrium
closely linked loci will show non-random association of alleles at linked loci. when you get farther from the mutation then the assortment of alleles is more random, but close by you have the same alleles almost always.
what if you have equilibrium of alleles and you want to know the prob. of a specific haplotype?
just do the “and” rule of probability for each of the individual frequencies for the alleles
how could we identify linkage disequilibrium?
see a occurence of a haplotype that is not equal to the product of the individual alleles…look for linkage disequilibrium.
what does linkage disequilibrium mean for the location of two alleles?
the two alleles are very close together on the chromosome.
what is a polygenic mode of inheritance
many genes affecting a trait
what is multifactorial inheritance?
there are multiple genetic and environmental factors that affect a trait
how many factors affect height?
180 loci that affect height
the threshold multifactorial model
many multifactorial traits and environmental factors are build up until you get above a threshold and then you will actually manefest disease.
how can the multifactorial threshold model explain the difference in occurence in males and females?
the threshold is different for male and female, for example the threshold for a female may be higher so that there must be more “liability factors” for a female to be affected
why would a female be more likely to pass on a pyloric stenosis?
they require more liability factors to get above the multifactorial threshold and so have more to pass off to offspring!
why would females be more likely to pass on autism?
4:1 ration of male to female occurrence, so if a female has it they must have more liability factors that they can pass on to offspring.
the factors for autism…number of genes.
more than a hundred different loci
what is the multi-factorial threshold model
there are a great number of liability factors that can add to give a phenotype but that phenotype will not manifest unless you get above a threshold of a number of liability factors.
