over the past few months, commenter chris davies has left several interesting comments here on the blog about hla haplotypes (see here and here and here and here for example) — something about which, like so very many things, i know absolutely NOTHING.
i asked chris if he’d help alleviate my ignorance by writing a post on the topic, and he has graciously obliged (thanks, chris!). so, without further ado, here’s chris’ introduction to hla!:
An Introduction to HLA (Human Leukocyte Antigens)
I would like to thank HBD Chick, who recently asked me if I wanted to write a guest post here about Human Leukocyte Antigens (HLA). I have been a reader of this blog for several months now, and I really enjoy it. This blog is among the most innovative of the HBD-related blogs out there and takes a completely different approach to the subject. So it is a pleasure to write a post here, as I don’t write a blog myself.
In the comments section on some posts here recently I have talked about ‘HLA haplotypes’. I have had an interest in HLA haplotypes for a few years, following discussions with a molecular biologist who writes (or rather wrote) in newsgroups including Usenet. But what are ‘HLA haplotypes’, and more importantly what is their usefulness or relevance to those of us with an interest in ‘HBD’?
‘HLA’ means Human Leukocyte Antigen. The HLA system is simply the name given to the human version of the Major Histocompatibility Complex (MHC). MHC genes are found in most vertebrates, and this group of genes can be found on chromosome 6.
HLA genes are important in immune function and disease defence. There are three classes: Class I (A,B,C); Class II (DP, DM, DOA, DOB, DQ, DR); and Class III. All play different roles.
In addition to conferring resistance or susceptibility to various diseases and conditions (eg autoimmune diseases, such as type I diabetes), they are also vitally important in organ and bone marrow transplants. For example, if a donor is not a close enough match in terms of HLA, an organ could be rejected. Because diversity of HLAs in human populations is a part of disease resistance, it is very uncommon to find two unrelated individuals with identical HLA molecules at all loci.
In addition, it has been claimed that HLA may play a role in human mate selection through people’s perception of the odor of other people.
HLA haplotypes are like strings of HLA genes by chromosome, with one being inherited maternally and the other paternally. A multigene haplotype is a set of inherited alleles covering several genes, or gene-alleles. Common multigene haplotypes are generally the result of identity by descent from a common ancestor. As distance from the ancestor increases, chromosomal recombination causes multigene haplotypes to fragment.
An example of an HLA haplotype is shown below:
A*01:01 ; C*07:01 ; B*08:01 ; DRB1*03:01 ; DQA1*05:01 ; DQB1*02:01
[Which by serotyping, is more simply: A1-Cw7-B8-DR3-DQ2].
This particular haplotype btw is found at high frequency among people of North-West European descent, including Irish, British, Dutch, Germans, Scandinavians, and of course a high percentage of Americans and Australians. It is associated with autoimmune disorders like coeliac disease, and allergic diseases like hayfever and asthma.
In addition to medical use, HLA haplotypes can also be used as a means of tracing migrations in the human population as they are like a fingerprint of an event that has occurred in evolution.
So alongside Y Chromosome DNA and Mitochondrial DNA (mtDNA) markers, HLA haplotypes are useful tools for molecular anthropologists in determining evolutionary links between ancient and modern human populations. They also help to determine closeness of relationships between or within populations, and commonality of geographical origin between groups. Therefore patterns of migration and settlement can be traced, giving insight into how contemporary populations have formed and progressed over time.
Because the HLA system is under selection, diversity in HLA should be looked at in conjunction with other markers like Y-DNA and mtDNA in building a bigger picture when tracing migrations of modern humans.
However, HLA has several advantages over Y-DNA and mtDNA. mtDNA is often biased towards the founders in a core population and can show a punctuated distribution, while Y-DNA is biased more towards relatively recent migrations, and with both of these markers the effects of genetic drift are more rapid. With HLA there is intense heterozygous selection which works to preserve diversity.
Also with HLA, one tends not to see a punctuated distribution of haplotypes across geographical regions between groups, but rather one sees a fluidity of migrations tracing back to their original source population. Examples of this occur when one looks at diversity of HLA in northern Africa, which appears to be the source for a number of haplotypes that migrated into Europe in the Holocene. This picture is less clear from looking at mtDNA or Y-DNA data only.
Finally, the other advantage of HLA is the sheer volume of data available. [See: www.allelefrequencies.net]. The numbers of people worldwide who have been typed for HLA are huge. There are nearly 22 million donors and blood cord units in the BMDW (Bone Marrow Donors Worldwide) database, encompassing many different ethnicities and nationalities with hundreds of thousands of HLA alleles and extended haplotypes identified. Y-DNA and mtDNA cannot offer this volume of data. Whether used for tracing ancient human migrations, or researching diseases in different populations, this data can be extremely helpful.
The association of HLA haplotypes in populations with certain diseases in Western countries is interesting to consider from an HBD perspective. For example, if resistance or susceptibility to obesity, heart disease, diabetes, breast cancer, etc. are all affected by HLA type, then there could be wildly varying outcomes between different population groups, in addition to the effects of environmental or lifestyle factors.
This in turn could have serious implications. For example, certain disease-related charities’ fund-raising campaigns are aimed at convincing the general public to donate cash on the basis that everyone is almost equally at risk from that particular disease, when different ethnic groups living in the same country with the same lifestyle may often vary in risk considerably from very high risk down to very low risk, with HLA type being an important determining factor. But the charity may not publicise this information in order not to jeopardise their fund-raising. This, I should stress, is speculation on my part however.
If want to find out more about Human Leukocyte Antigens, please refer to some of the sources listed below:
- The Allele Frequency Net Database (AFND). A database and online repository for immune gene frequencies in worldwide populations: [www.allelefrequencies.net]
- “Tracking Human Migrations by the Analysis of the Distribution of HLA Alleles, Lineages and Haplotypes in Closed and Open Populations.” [Fernandez Vina, M. et al, 2012].
- “HLA 1991: Proceedings of the Eleventh International Histocompatibility Workshop and Conference” (Volumes I & II) [Kimoshi Tsuji; Miki Aizawa; Takehiko Sasazuki] Oxford Science Publications, 1991.
- “HLA-Net: A European Network of the HLA Diversity for Histocompatibility, Clinical Transplantation, Epidemiological and Population Genetics.” [www.hla-net.eu].
- “AHPD: Analysis of HLA Population Data to Reconstruct the History of Modern Humans and Infer the Role of Natural Selection.” [geneva.unige.ch/ahpd].
- “Challenging Views on the Peopling of East Asia: the Story According to HLA Markers.” [Di D, Sanchez-Mazas A.]. Am J Phys Anthropol. 2011 May; 145(1):81-96.doi:10.1002/ajpa.21470.Epub2011Jan4. PMID:21484761 [Pubmed – indexed for MEDLINE].
- Wikipedia: “Human Leukocyte Antigen.”
- Wikipedia: “Major Histocompatibility Complex.”
(note: comments do not require an email. gene map of the human leukocyte antigen (hla) region!)