Talk:Linkage disequilibrium

message: I would like to make a small suggestion to improve the article.  In the last paragraph of the introduction it says:-
: For example, some organisms (such as bacteria) may show linkage disequilibrium because they reproduce asexually and there is no recombination to break down the linkage disequilibrium.
There is recombination in bacteria, as occurs during Natural Competence for example.  I do not question that bacteria do show LD and that this has something to do with the fact that they reproduce asexually (I am not an expert on LD, so I take it on trust that this is the case).  Could this explanation be expanded upon, or reworded in such a way so that does not imply that recombination does not occur in bacteria. The Red Lexicon (talk) 14:34, 17 September 2010 (UTC)
thread_title: Linkage Disequilibrium in bacteria

message: I am an statistician and probably my remarq is not of great interest but, in a statistical point of view, it should be better to avoid
NON-RANDOM association (because the association of alleles is a random process) and to replace the above expression by NON-INDEPENDENT association  —Preceding unsigned comment added by 147.99.111.194 (talk) 08:52, 5 October 2010 (UTC)
thread_title: Linkage disequilibria

message: I removed the statement "and their genetic distance", since it is not relevant to LD. Lower linkage disequilibrium is expected in data sets for loci the farther they are apart. However, LD reflects covariance between alleles thereby comparing joint occurence with a product distribution - irrespective of distance. -sboehringer
Could somebody put up a linkage disequilibium plot with a desciption of what this plot shows.  Thanks.  —Preceding unsigned comment added by Sarhas (talk • contribs) 19:47, 24 June 2008 (UTC)
thread_title: LD

message: The statement that
:When extending these formula for diploid cells rather than investigating the gametes/haplotypes directly, the laid out principle prevails, the recombination rate between the two loci A and B must be taken into account, though, which is commonly denoted by the letter c.
seems wrong to me.  Aside from whether "the laid out principle" is good English, the estimate of D can be made without knowing anything about the recombination fraction between A and B (for example, by the EM method of Hill,  1974). Felsenst 01:34, 1 January 2007 (UTC)
replies: text: Agreed, 'the laid out principle' needs to go. Also, recomination rate is usually denotated by r (in my expierance), the article I think should use that since r makes symbolic sense more easily. As for D, perhaps D' was ment (as in the value of D for the next generation) D'=(1-r)D  ??? But you are correct, D can be calculated without r. D is the devation from 1 of the sumation of all possible haplotype frequencies. r decays D, which is why I think the above article statement should be changed to apply to D'. [haplotypes A1B1=a,A1B2=b,A2B1=c,A2B2=d] ... D=(ad-bc) right? Could you toss the EM method into this thread? --Mike Spenard 07:03, 1 January 2007 (UTC)
replies: text:  I think you must have meant something else when you said "the [sum] of all possible haplotype frequencies", since the frequencies of everything always adds to 1.   D is the frequency of a particular (two-locus) haplotype (say A1B1), minus the expected frequency of that haplotype if the alleles at the two loci are distributed randomly, which is p(A1)p(B1). Felsenst 23:43, 4 September 2007 (UTC)
thread_title:  Diploids 

message: I think there is a problem with the section on δ.  As stated, the formula for it is backwards -- it ought to be  h12 - p1 p2, not the other way around.  Furthermore there is the puzzling issue of why we have the two measures D and δ when they will be exactly the same number. Can someone enlighten me about this? (I have written a number of papers on linkage disequilibrium starting in 1965 so I believe that I know what I am talking about, but maybe I've missed something). Felsenst 05:38, 29 August 2007 (UTC)
replies: text: Let me answer my own question.  p1 p2 - h12  is not correct.  But I had failed to notice that it was h12.  However it is more conventional to express it in terms of  h11, p1, and  p2  whereupon it would be  h11 - p1 p2.   To express it in terms of  h12  the correct formula would be  p1(1-p2) - h12. But all this notation is not clear becase  h11  is the frequency of haplotype  A1B1, but  p2 is described as the marginal frequency at the B locus so that it is unclear whether it is for the B1 or the B2 allele.  Felsenst 22:35, 26 September 2007 (UTC)
thread_title:  What's with δ ? 

message: In the discussion of the r2 measure of disequilibrium it is said that "This however is not adjusted to the loci having different allele frequencies."  The whole point of r2 is that it is adjusted for gene frequencies, so this is incorrect. It may not be the best possible way of adjusting, but it tries to do so. This is followed up by a statement that if we take the square root of r2 and give it the sign of D, we get the measure D'.  Which is fine, except that this isn't true (try doing both the r2 and D' computations in a case with gene frequencies away from 50% at one or more of the loci and you will see that they don't come out the same). Felsenst 07:08, 6 September 2007 (UTC)
thread_title:  What's with r<sup>2</sup> ? 

message: Things seem to be improving.  Some concerns:
# I am not sure why the haplotype frequencies have to be carefully described as "relative frequencies".  They don't add up to 1?  Actually they do add up to 1 (if there are two alleles at each of the two loci) so describing them as relative is not helpful.  They are absolute frequencies, not relative frequencies.
# Lewontin and Kojima's paper gives LD its name.  That was eliminated.  I am not sure whether they were the first to use the letter D, as the reference in the text now implies.
# I am told by Monty Slatkin that the historical attribution to Robbins is in fact incorrect -- LD and its mathematics was introduced slightly earlier in a paper by H. S. Jennings, who was the great pioneer of genetics of protists.
Some of the problems I noticed earlier are still around but things are improving. Felsenst (talk) 14:16, 12 December 2007 (UTC)
thread_title:  Linkage disequilibrium measure, D 

message: I have revised the explanation of why D approaches zero with random mating.  The reference to Crow and Kimura for the derivation has been removed, as most readers will not have access to the book.  I still don't understand why linkage disequilibrium is described as two quantities \delta and D, with the former defined wrongly. Felsenst (talk) 00:10, 4 September 2008 (UTC)
thread_title:  Explained why D goes to zero 

message: Sorry folks, for altering your prose but I made quite a few changes.  The misbegotten quantity \delta which was misdefined is gone, some wording improved, the discussion of the relationship
of D' and r and whether they are or are not corrected for gene frequencies is changed.  I hope you will find it in your hearts to forgive me. Felsenst (talk) 19:54, 5 September 2008 (UTC)
thread_title:  "Lost it" and made many changes 

message: We now need a section showing how in diploids having LD means that we expect an association between genotypes at two loci (I removed a mention of diploids because it got this mixed up with the effect of recombination,
something that happens in both haploids and diploids).  We also need a section of multi-locus disequilibrium measures (at least, mentioning that they exist). Felsenst (talk) 19:59, 5 September 2008 (UTC)
replies: text: I am adding a section using Burger/Nagylaki notation for multilocus linkage disequilibrium, but the notation is fairly complex (possibly inappropriate for an encyclopedia).  Can you point me to any better sources for this?  — Preceding unsigned comment added by Trashbird1240 (talk • contribs) 20:47, 13 January 2012 (UTC)
thread_title:  Needed 

message: A bot came along and changed a reference (one which I had added, so I feel paternal about it) to look like this:
:Robbins, R.B. (07/01/1918). "Some applications of mathematics to breeding problems III". Genetics 3 (4): 375–389.
Now exactly why is it important to know that this journal issue was published on 1 July 1918?  It's not a newspaper issue.  It's a scientific journal volume (and volume 3 of that journal consisted of issues published at various dates of that year).  No one but this overenthusiastic bot makes references like this. How do we stop it?
It seems to have been reacting to the reference having had a "year" tag but not a "date" tag.  So it put in the date.  What next?  Hours, minutes, and seconds? Felsenst (talk) 12:25, 14 October 2008 (UTC)
thread_title:  Ludicrous reference 

message: In my opinion, for what it's worth, the HLA examples are too long, too complex, and have too much technical jargon (such as "codominant") that the reader may not know.   On addition there are distinctions not explained, such as LD within populations and LD among (between) populations -- the example used in the second paragraph of this page is between-population LD and the examples used in the HLA section of the article is within-population LD.  That whole issue is not yet explained but the distinction is important.   In the figure that has appeared at the top of the article the LD comes from assortative mating, an issue barely touched on in the article.   The LD in that example is described as "randomly generated" without making it clear whether this is due to random genetic drift (it is mostly due to assortative mating with the differences between curves due to drift).   In general, the article is getting too long and messy and is moving away from simple, lucid explanation. Felsenst (talk) 10:54, 18 September 2010 (UTC)
replies: text: I agree.  Ideally the article would have more prose and less mathematical notation.  The amount of jargon should be decreased.  Brief explanatory phrases should be provided upon introduction of remaining jargon.  The worked examples that make up much of this article run counter to the WP:NOTTEXTBOOK policy by using "systematic problem solutions as examples". Emw (talk) 13:41, 18 September 2010 (UTC)
thread_title:  HLA stuff too complicated and too technical? 

message: I have published a number of changes that I hope will improve this page. It is not intended to be anywhere near exhaustive; there is much more to be done (to which I hope to contribute someday).
1. I have added a reference to the term "gametic phase disequilibrium". I have cited Falconer & Mackay as the source; if anyone knows of a better one, please change it.
2. I have combined the paragraph beginning "The level of linkage disequilibrium is influenced by a number of factors" and the paragraph on Finnish disease heritage.
3. I have tried to improve some of the math typography, with indifferent success.
4. I have restated the definition of Lewontin's D. The previous version was incorrect, as a negative D would become a positive D' under that definition.
5. I have changed the section heading "Prevalence" to "Example: Human Leukocyte Antigen (HLA) alleles". I found the original heading rather confusing. I have not spent any time on the question of whether that section should exist, or whether it should be replaced by a different example.
6. I have corrected a number of minor typos and grammar or spelling errors.
I hope that this will be regarded as an overall improvement, and welcome any comments.
--Glipton1 (talk) 20:29, 25 May 2011 (UTC)
replies: text: Thanks.  I'm embarassed (as a "pro") to have gotten the D' formulas wrong.   So in expiation I have corrected the formula for  r  as it only calculated r-squared and did not say what square root to take.  The Finnish HLA example still has the defects I complained about above -- leaving us confused about within versus between-population disequilibrium, for example, and just being too damn long. Felsenst (talk) 03:10, 26 May 2011 (UTC)
replies: text:  Thanks for the comments. I have ambitions to revise or replace the HLA example, but, like everyone else, my time is limited. I will do what I can. I am not a particular expert on LD or population genetics, but I feel that such a central concept as LD merits a thoughtful and careful treatment in Wikipedia.--Glipton1 (talk) 17:37, 26 May 2011 (UTC)
replies: text:  ... particularly since it is a concept that is not so easy for a lot of us to grasp. Felsenst (talk) 13:08, 27 May 2011 (UTC)
thread_title:  Incremental Revision 

message: My original wording that the copies of A and B that are put together by recombination are to be regarded as independent of each other because they were located on "different haplotypes", has recently been changed by another user to "different loci".   The phrase "different haplotypes" was probably unfortunate, I agree.  But "different loci" does not work either.   They are independent because they were on haploid genomes that were independently drawn from the population.   If they had been on the same haploid genome, and nonindependent because they were in linkage disequilibrium, they still would be at different loci, so that is not a reason for them to be independent.   But by saying "different haplotypes" I improperly implied more than just that they were on different copies of haploid genomes.
So what is  good phrase to use here?  Suggestions?  Felsenst (talk) 22:10, 8 August 2011 (UTC)
thread_title:  Independent because of what? 

message: I have some proposed changes to the introduction for clarity and accuracy. The changes are up on my sandbox User:PaulGNelson/sandbox. Please let me know what you think.   — Preceding undated comment added 20:44, 19 April 2015 (UTC)
replies: text: Oops, I didn't see this comment before I substantially revised the intro. My apologies! See what you think of my version. I don't think your proposed example is an example of linkage disequilibrium (deviation from the Hardy-Weinberg ratios), which applies to two alleles at the same locus rather than alleles at different loci. There should definitely be a basic example but maybe it would be better if we simplified (and renamed) the "Definition" section since that is the classic example (i.e. a two locus, two allele model). (BTW, to sign your comments use four tildes in succession) Jasonbertram (talk) 05:39, 20 April 2015 (UTC)
thread_title: Changes to introduction

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thread_title:  External links modified