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 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,ckthe 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

<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.