Question

How can genetic linkage be used to map disease-associated loci? Use the identification of CFTR as the causative loci for CF via linkage analysis as an example in your answer.

GWAS and linkage analysis are both used to map disease-associated loci. Compare and contrast the two techniques.

Guys please help me with these two questions. They are linked and Im struggling to find accurate answers.

Answer 1

Linkage maps represent the genetic locations of loci on the chromosome.
They are constructed based on recombination frequency values.
Recombination frequency is directly proportional to the distance between two loci.
Greater the recombination frequency value, greater is the distance between the two loci.

Recombination frequency = (Number of recombinants/Total progeny) X 100

In the given case, the recombination frequency between Marker P and CFTR locus is determined by analyzing the progeny phenotypes and their genotypes at both CFTR locus and the marker P locus.
Let us assume that the recombination frequency between CFTR locus and P = 23%

In the same recombinant progeny, calculate the recombination frequency between Marker Q and CFTR locus.
Let us assume that the recombination frequency between CFTR locus and Q = 13%

In the same recombinant progeny, calculate the recombination frequency between Marker R and CFTR locus.
Let us assume that the recombination frequency between CFTR locus and R = 3%

We can construct a genetic map from the above information as,
P---10%---Q---10%---R--3%--CFTR

GWAS = Genome-Wide Analysis studies.
It is a whole-genome analysis study comprising of genomic analysis for several individuals of a given population.
This will reveal the association between a particular allele present in the population to the phenotype concerned.
It requires genome sequencing and bioinformatic analysis. It is relatively a new method.

Linkage analysis is a traditional method used to determine the relative location of a gene in the genome based on recombination frequency values.