Inheritence of MHC genes

Figure 1: Mendelian inheritance of HLA alleles. In this case the alleles are A1, A2, A3 and A4. The parents genotype is shown at the top. Following meiosis, the parents produce the gametes shown. The gametes fuse to form the four alternative offspring. The genotypes of the offspring are shown in the lower part of the figure. Most offspring will be of these four types, but rarely a cross-over event will have occured and the genotype will be different.

A gene is the basic unit of inheritence. The geno-type of an individual is their genetic make up. The pheno-type is the physical expression of the geno-type. Individuals vary due to differences in their genes. Each gene exists in many different forms, which are termed alleles.

The inheritence of these genes follows simple mendelian patterns with one allele being inherited from the father and the other from the mother. Numerous different alleles of each gene are found and these are designated as HLA-A1,2,3 .... See figure 1.

The class-I MHC genes are HLA-A, HLA-B and HLA-C. The class-II MHC genes are HLA-DR, HLA-DP and HLA-DQ. As described above there are multiple alleles of each of these loci, for instance HLA-A1 and HLA-A2. Each parent normally has two pairs of six MHC alleles. The site of the MHC genes is on 6p, the short arm of chromosome 6. The number of chromosomes in somatic cells (not gametes) is 22 pairs of autosomes and one pair of sex chromosomes. Each of the copies of chromosome 6 thus carries three class-I alleles and three class-II alleles. So there will be twelve MHC alleles in each somatic cell. One set of six alleles is inherited from the mother and the other six from the father. The six alleles from each parent are termed the haplotype.

The maternal haplotypes may be; [A1-C1-B1--DR1-DQ1-DP1] and [A2-C2-B2--DR2-DQ2-DP2]. So the maternal gametes contain either [A1-C1-B1--DR1-DQ1-DP1] or [A2-C2-B2--DR2-DQ2-DP2]. The paternal haplotypes may be; (A3-C3-B3--DR3-DQ3-DP3) and (A4-C4-B4--DR4-DQ4-DP4). So the paternal gametes contain either (A3-C3-B3--DR3-DQ3-DP3) or (A4-C4-B4--DR4-DQ4-DP4). The offspring then would be [A1-C1-B1--DR1-DQ1-DP1] : (A3-C3-B3--DR3-DQ3-DP3), [A1-C1-B1--DR1-DQ1-DP1] : (A4-C4-B4--DR4-DQ4-DP4), [A2-C2-B2--DR2-DQ2-DP2] : (A3-C3-B3--DR3-DQ3-DP3), [A2-C2-B2--DR2-DQ2-DP2] : (A4-C4-B4--DR4-DQ4-DP4).

Occasionally a cross-over event may occur in one of the parents and the entire haplotype will not be inherited as a unit. For instance in the maternal haplotypes above, [A1-C1-B1--DR1-DQ1-DP1] and [A2-C2-B2--DR2-DQ2-DP2]. Without a crossover event the gametes are [A1-C1-B1--DR1-DQ1-DP1] or [A2-C2-B2--DR2-DQ2-DP2]. But with a crossover event they may be [A1-C1-B1--DR1-DQ2-DP2] or [A2-C2-B2--DR2-DQ1-DP1], here a crossover has occurred between the DR1-DQ1 region so that DQ2 and DP2 join the first haplotype.