Linkage Disequilibrium in Genetics: Definition & Difference

[dpsguy]

What is linkage disequilibrium in genetics? How is it different from linkage?

 

[Monique]

Linkage disequilibrium mapping is something you do in populations: you look at the non-random association of markers, which forms haplotypes (stretches of DNA that have the same markers between individuals). That means that a piece of DNA is co-inherited with a phenotype of interest.

It is linkage disequilibrium (LD), because you can predict the state of one marker if you know the state of the marker next to it (the markers that are used are SNPs). If something is in equilibrium, the distribution would be random.

Linkage is something you do in families (there has not been enough time for chromosomes to be shuffled around to look for LD). Here you look at the co-inheritance of a marker to a phenotype, the closer the two are together, the tighter the linkage between the two will be. If the two are far apart, recombination can reshuffle the physical position of the and linkage is lost.

The resolution of linkage is much lower than LD, so linkage is usually used for rough mapping and LD is used for fine-mapping or candidate-gene studies.

 

[dpsguy]

I'm sorry, but I'm a little confused here. Do you mean that when we are studying LD we are actually studying linkage in a population(instead of a family) and across several generations?

It is linkage disequilibrium (LD), because you can predict the state of one marker if you know the state of the marker next to it (the markers that are used are SNPs). If something is in equilibrium, the distribution would be random.

What do you mean by "state" of the marker?

 

[contrio]

u been using wikipedia too much

dpsguy, if u know normal linkage, then u are almost there. state/loci, same meaning. The phenomenom can only analyzed in populations so u have more data to compare with each other, that's all.

 

[Monique]

LD is not the same as linkage. State and loci also don't mean the same thing. The state of a marker is whether the polymorphism is A or B. A locus is a location on the genome.

For linkage you test markers that are highly polymorphic, so that there is a lot of variation in one family and you can test wether a certain marker co-segregates with you phenotype of interest. Essentially you are looking at the segregation of a whole chromosome, where you use recombination events to narrow down the locus (piece of chromosome) where the marker and the phenotype co-segregate.

For LD you use markers that are very stable, so that you can look at a population level at their distributions. Here you are looking at tiny fragments of chromosomes, you can imagine that huge numbers of recombination events have happened in a population that reshuffled the chromosomes. A random distribution would mean there is an equilibrium. If there is an ancestral piece of DNA that is cosegregated with your phenotype of interest, you have LD. In this analysis you look at haplotypes, a whole series of markers with the same state that are co-segregated.

As I said, both methods have different resolutions.

 

[contrio]

alright i was a bit off, sorry about that

 

[dpsguy]

alright i was a bit off, sorry about that

a bit off!

 

[dpsguy]

Thanks Monique! I think I get it now,more or less. I guess it would be correct to say that studying linkage can help us find the locus related to a given phenotype while LD helps us establish the gene or even a gene variant, in case of a mutation(?)

 

[Monique]

Thanks Monique! I think I get it now,more or less. I guess it would be correct to say that studying linkage can help us find the locus related to a given phenotype while LD helps us establish the gene or even a gene variant, in case of a mutation(?)

Yes, that is correct.