Blood Group Inheritance and Paternity Testing

Resources: Protocols; Presentations; Wikipedia

1) In the inheritance of the AB0 blood groups three alleles, i, IA, and IB, situated on chromosome 9 determine the blood group of the individual. The i allele is recessive, while the other two are codominant.

These alleles encode enzymes (transferases) catalysing the attachment of antigens (presented in table) to the surface of red blood cells. Note: Recessive homozygotes (ii) do not bind any of the antigens.

2) H substance is a molecule present in the membrane of all erythrocytes. It is involved in the AB0 blood groups’ manifestation in the phenotype. H substance serves as the anchor to which A antigen(N-acetyl-D-galactosamine) and/or B antigen(D-galactose) are attached.

The dominant, H, allele encodes for a functional H substance, whereas the recessive, h, allele codes for a non-functional anchor. This allele is situated on the 19th chromosome.
Recessive homozygotes, hh, cannot bind either A or B to their surface. The blood group of such an individual appears as 0 (Bombay Type), although it is not.

3) The Rh blood group system is determined by three genes on chromosome 1. It involves many antigenes on the erythrocyte surface among which 5 antigens (D,C,c,E,e) are the most important. The commonly used terms Rh-positive or Rh-negative refer to the presence of the D antigen.

The dominant allele, D, is responsible for the presence of a functional D antigen on the surface of the erythrocytes (Rh-positive). Recessive homozygotes, dd, are therefore Rh-negative.

4) The MN blood group system is controlled by one gene on chromosome 4 with two codominant alleles M and N. Therefore 3 blood groups can be distinguished: MM, MN, and NN.

Blood group antigens of different systems each show monogenic autosomal inheritance, and therefore they can be used for analysis of family relationships (such as excluding a man from paternity). The compatibility of the AB0 system antigens and the Rh factor are also very important for blood transfusion (similar to the HLA antigens of the major histocompatibility complex bound to the surface of all cells, which are crucial in organ transplants).

Paternity testing:

  • Genotypes of the mother, father and child are compared
  • A test based on matching blood types is easier and cheaper to perform, but it is less reliable. Therefore
  • A more reliable test can be used, such as matching HLA (human leukocyte antigen).
  • DNA testing (Genetic fingerprinting) is however the most reliable paternity test. The most often method of genetic fingerprinting is matching the VNTRs (Variable number of tandem repeats) and the length of those fragments after restriction digest (RFLP – restriction fragment length polymorphism)

Note: The source of genetic material is usually DNA isolated from peripherial blood leukocytes, or possibly buccal mucosa epithelial cells.

Extra: Cancer Genetics

  • Only 5 to 10% of the cancers are hereditary
  • More than 20 hereditary cancer syndromes have been identified so far
  • A germinal mutation of a certain critical gene is often responsible
    • Tumour-suppressor genes such as
      • BRCA1; BRCA2; PTEN – in breast cancer
      • Rb1 – retinoblastoma
      • WT1 – Wilms’ tumour (infant kidney tumour)
      • APC; MSH2; MSH6; MHL1 – tumours of large and small intestine, colorectal carcinoma
  • but it could also be a hereditary predisposition.