Again, these serotype articles are not being written in a way that an educated, general reader can understand. As an example, this is the lead paragraph with annotations of where some clarification could go a long way:
- HLA-B53 (B53) is an HLA-B serotype.<What does this mean? Explain what an HLA-B serotype is.> The serotype identifies the more common HLA-B*53 gene products.<Confusing. What are "gene products"? How does it identify them?>
- Gene products has its own page. Serotype has its own (very poorly written) page. A serotype is an antibody that recognizes antigens on the surface of a living cell, human, bacteria. Serotypes can be divided in natural serotypes, for example you are infected with bug X and you develop antibodies that recognize bug X and when I put a slide of bug X with your antibodies under a microscope that sees the probed-antibody, bug X lights up like a christmas tree.
- When humans started transplanting tissues between each other the artifactually created these reactions, not to bacterial cells, but to human cells. So that when I take someone who rejects a kidney, and I take their Sera and purify their antibodies and separate them, I can sample your cells and some of these antibodies may react to your cells. Way back in the 1970s that meant you had some similarities with that person who donated the transplant. Later on these similarities were broken down and explained.
When PCR came along the underlying genetics was discovered.
- The B53 sequence is identical to B35 but short sequence specifies a Bw4 rather than a Bw6 motif (as found in B35), indicating B53 is a recent product of gene conversion.<What is "gene conversion"? What is B35? Another serotype? Say so! What is Bw4, and what does specifying it mean?> This suggests an origin for HLA-B53 involving a gene conversion of HLA-B35 by an allele containing this Bw4 sequence.
- PLEASE!..gene conversion has its own page.
- HLA-B35 page is not yet written. Bw4 page is not yet written, specificity is the antibody reaction, however that sentence was abbreviated from a paper and will be rewritten. Bw6 page is not yet written, HLA-B*5301 is a gene (called an allele because it is a minor variant of a major gene, HLA-B) at the HLA-B locus on chromosome 6p21.3 This gene was created by gene conversion (IOW there was an attempt to recombine a maternal and paternal chromosome 6 at this very locus-allele HLA-B35 that aborted after making a few changes, this is the way gene conversion has been explained to me by a leading authority on recombination. The source for these changes was so small that we cannot identify the whole 'Donor' gene-allele, only a motif shared by many alleles.
- I may elaborate on gene conversion for HLA-B on the Bw4 and Bw6 pages once created. However I wish to have a list of alleles in which these motifs have been contributed first.
- If you are deeply interested what is understood about gene conversion please read Science 1996, Parham and Ohta (Try a wiki search you can probably find the full reference). Gene conversion in humans was not commonly recognized until Watkins and Peter Parham pointed this out, it has not really been characterized or described mechanistically. Its just some odd recombination that happens alot at HLA.
- The other form evolution at HLA are Single nucleotide polymorphisms, long range homologous recombination, gene duplication and deletion (examples are HLA-DRB loci)
- What should be understood are two specific factors regarding HLA-B evolution
- 1. It is very rapid, this creates much confusion, more rapid evolution creates more complexity.
- 2. That we ascertained information starting from the end points of the population, Essentially NW Europe, and have been working backwards into africa were this end-point diversity originated. As we have crawled back into africa, the complexity has increased rapidly, the number of new alleles and new groups supercedes the ability to create good serotype recognition, and in fact the only reasonable way to identify these genes is with Sequence Specific Primer PCR (SSP-PCR). The process is not yet complete, 3 core groups have not been typed and I am certain based on X-linked and mtDNA that we will find HLA groups that are only found in Tanzania, Zambia and/or the Congo.
- My goal is the reduce all of this to the simplist most essential information regarding each type, and expanding that information as needed when new information comes in.
What is an HLA Serotype
(Defined clearly on the HLA page, BTW) The basic problem is that the definition given for Serotype (Serovar) on wikipedia is not correct, it is incomplete. Rome was not built in a day, and I will have to think about how best to deal with that, Serovar is not the word used in the HLA literature, and so someones pet definition of Serotype is probably at play.
If you know what an HLA-B serotype is then you know what HLA-B53 serotype is. When I am done the HLA-B page will be rewritten so that each of the serotypes are ordered and so that it will be known as a variant. Note I am not the author of the HLA-B page either. Nor the HLA-B27 page. So . . .
For now, however the pages for each will be created. HLA-B set is the most massive of these.
Serotypes were defined by Graft versus Host Disease, not by infection. But the Serotype page on wikipedia makes no distinction.
HostVsGraftDisease(Antigen) -Allotypic host---> Antibodies to HVGD antigen, if the graft is then the B53 gene product, the antibodies are to B53 and therefore you have a serotype. Antibodies from the Host can be used to identify aspects of the grafts. This includes HLA-A, B, Cw, DR, DP, DQ antigens. IOW one Host can have antibodies to a number of antigens.
ONce this was determined Workshops create a systematic system all considered w
w1 ---> A1
w2 ---> A2
w3 ---> A3
w4 ---> Bw4 motif
w5 ---> B5 ------> B51, B52
w6 ---> Bw6 motif
w7 ---> B7
w8 ---> B8
w9 ---> A9 -----> A23, A24
w10 ---> A10 ----> A25, A26, A34, A66
w11 ---> A11
w12 . . . . . . .
And so on as the science evolved. As and Bs. Why Some become A and some became B.
This history is horribly confusing, not well documented, except the behind closed doors work done at conferances, that eventually resulted in a nomenclature. Why is the nomenclature so difficult.
HLA-A, B and C do the same thing, three loci. At each loci there are 100s of genes
Currently there are:
There are more allelic variants for HLA genes than there have been alleles typed for most other gene-population studies! But it would be foolish to discuss every single allele on wikipedia, therefore only alleles in which some statistics has been done, and the only statistic that I am aware of is the serotyping studies.
HLA-B for instance if you look at the http://www.anthonynolan.org.uk/HIG/lists/class1list.html you will note that HLA*B15 one of the 30 or so broad antigen groups has numbered alleles from 1501-1599, and from 9501 to 9539 some of them later abandoned for approximately 130 protein variants of HLA*B15 allelegroup that was defined by the B15 serotype, the serotype was also expanded to include B62, B63, B70, B71, B75 serotypes that distinquishes some but not all of these alleles.
So that for instance B*1501 is recognized by B15 and B62. You might ask why would anybody use such a system with SSP-PCR. In Arabia and Africa, there are serotypes recognized that cannot yet be determined by SSP-PCR indicating that many more new sequences exist. Therefore, serotyping and PCR can be used in cooperation to determined what needs to be sequenced. If you go to Ireland you can sample 1000 people and find no need to sequence 1 individual. You can go to Yemen or Southern Iran, and 1 in every third person, you might have to sequence and HLA gene. So . . . .fast evolving gene needs fast evolving science to catch up.
This early work was started in the 1970s when the genes and genetic loci were unknown. It was discovered there was a locus for HLA-A and HLA-B over time this group was further populated with new serotypes and then a third locus HLA-C was identified and although the serogroups are pretty final the convention of HLA-Cw has stuck. (Don't know why).
Not all the serotype groups in the human population have been identified. The region between South Africa/Namibia and Cameroon to Kenya has been poorly sampled, and many new alleles (probably double the current list) and a few new groups may be discovered. More than likely these will not be serotyped, as the SSP-PCR is replacing serotyping due to its obvious weaknesses. We know these areas will be hot spots because Harris and Tishkoff defined Tanzania and Zambia and genetic hotspots (mtDNA and X-linked loci) of diversity. So-called core ancestral population occupied these regions.
None the less the grouping of HLA antigens arepartitioned based on serotyping antibody recognition.
Complicated, reader doesn't really need to know this, its the same kind of information like why mtDNA haplogroup X is X and not Y. HvGD Antibody recognition is not a function of HLA-B its an artifact, but within each major serotype there is almost always one principle allele, which is convienient.
For very detailed understanding for the relationship of alleles to serotypes see the links provided in the Protein box on the side, and also see the Nomenclature of the HLA system, 2004. There is a reference within the page.
- This is great, but explanatory material belongs in the article itself, not on the talk page. — Brian (talk) 04:12, 15 October 2007 (UTC)
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