Glossary
TERMS
Allele frequency, Serotype frequency
HLA types are usually described as alleles or serotypes. Alleles
are represented in genomic levels and serotypes are represented
in protein levels (HLA types as determined by serological
studies).
HLA types are polymorphic and the known number of Alleles
increase yearly because of discoveries of new ones, developments
in experimental methods and strengthening in the recognition of
HLA typing tests.※1
Allele or Serotype frequencies indicate the ratio at which
alleles and serotypes exist in a population.
Expression frequency
When a genotype is a homozygote or there is loss of
heterozygosity (eg. A*24:02,－), only one kind of protein is
represented. In other words, the number of genotypes may differ
from the number of proteins that are represented.
Expression frequency indicates the ratio of each allele or
serotype that is represented in a population.
Haplotype
Haplotype is an abbreviation of “haploid genotype” (haploid
possibly derives from ‘half’). When there is mention of a whole
genome, it refers to a set of “uni-parental genotypes”.
In HLA, a haplotype means a set of loci (E.g. the set of HLA-A,
B, DRB1). Haplotypes are extremely important for transplant
immunology and anthropology.
Linkage Disequilibrium
Genetic linkage exists in HLA haplotypes. In other words, and in contrast to Mendel’s Laws, haplotypes are inherited in sets. There is disequilibrium with these linkages, and from the view of population genetics, it is apparent that certain haplotypes have significantly high frequency.
LD value, RD value
LD values and RD values quantify the ratio of linkage
disequilibrium. How to consider these values and the method to
equate their values are based on a method by Imanishi et al※2.
LD value (linkage disequilibrium value) is the difference
between the observed value and the expected value of haplotype
frequencies and is obtained by the following equation.
LD = HF（AiBjCk…）- aibjck…
・HF（AiBjCk…）haplotype frequencies
・ai,bj,ck…the frequency of each genetic locus
As shown in Table1 however, there are instances when each
haplotype frequency can have significant differences.
The above-mentioned formula implies that there is a scattering
in the index of only LD value.
Table1 HLA-A, B, DRB1 haplotype frequency
| A-B-DRB1 | Haplotype frequency | LD value | RD value | Rank |
|---|---|---|---|---|
| *24:02-*52:01-*15:02 | 8.468% | 8.033 | 0.786 | 1 |
| *33:03-*44:03-*13:02 | 4.081% | 4.057 | 0.737 | 2 |
| *24:02-*07:02-*01:01 | 3.746% | 3.627 | 0.654 | 3 |
| *24:02-*54:01-*04:05 | 2.609% | 2.238 | 0.312 | 4 |
| *02:07-*46:01-*08:03 | 2.003% | 1.988 | 0.573 | 5 |
| *11:01-*15:01-*04:06 | 1.281% | 1.259 | 0.397 | 6 |
| *24:02-*59:01-*04:05 | 1.062% | 0.968 | 0.535 | 7 |
| *11:01-*54:01-*04:05 | 0.958% | 0.866 | 0.116 | 8 |
| *24:02-*40:06-*09:01 | 0.866% | 0.630 | 0.146 | 9 |
| *26:01-*40:02-*09:01 | 0.843% | 0.754 | 0.100 | 10 |
RD value (relative linkage disequilibrium value) corrects this
phenomenon.
In other words, RD value (relative linkage disequilibrium value)
observes LD value in relativity.
RD value is determined by dividing the LD value by the maximum
absolute LD value can take.
RD = LD/｜LDmax｜
・（LD≧0） LDmax = Min{aibjck…}
- aibjck…
・（LD<0） LDmax =
Min{0,（aibjck…）-（the numbers
of loci-1）} - aibjck…
Min{} and Max{} are minimum values and the maximum values of the variable in {}.
When an LD value is positive, the maximum value of LD value
becomes the minimum value in each allele frequency because the
allele population parameter is equal to the haplotype population
parameter.
It is thought that the larger the value and closer the haplotype
frequency and the closer the RD value is to 1, the larger the
linkage disequilibrium.
Moreover, a negative linkage disequilibrium exists when an LD
value is negative.
※1 IMGT home page
※2 Imanishi, T., Tokunaga, K., Akaza,
T., et al (1991). Allele frequency and Haplotype frequency in
HLA genes in the Japanese population (the 10th Japanese HLA
workshop cooperation report),
Kyou no Ishoku (Today’s Transplants). 4Sippl.(2), 147-185.