Null Alleles ?

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taz's picture
Null Alleles ?


Why is it important that null alleles are detected? And why is it extra important in unrelated bone marrow transplantations?

I hope You can help me,

Fraser Moss
Fraser Moss's picture
Basic description from

Basic description from

A null allele is a mutant copy of a gene that completely lacks that gene's normal function. This can be the result of the complete absence of the gene product (protein, RNA) at the molecular level, or the expression of a non-functional gene product. At the phenotypic level, a null allele is indistinguishable from a deletion of the entire locus.

One example of a null allele is the 'O' blood type allele in the human A, B and O blood type system. The alleles for the A-antigen and B-antigen are co-dominant, thus they are both phenotypically expressed if both are present. The allele for O blood type, however, is a mutated version of the allele for the A-antigen, with a single base pair change due to genetic mutation. The protein coded for by the O allele is enzymatically inactive and therefore the O allele is expressed phenotypically in homozygous OO individuals as the lack of any blood antigen. Thus we may consider the allele for the O blood type as a null allele.

Regarding Null Alleles in Bone marrow transplants see

Tissue Antigens. 2005 Aug;66(2):93-8.

HLA class I null alleles and new alleles affect unrelated bone marrow donor searches.

Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA.

Unrecognized HLA null alleles or new alleles may affect the outcome of bone marrow transplants using unrelated donors. Some reports suggest that null alleles occur in the range of 0.003-0.07% (1, 2), which has led some transplant programs to stop performing serologic typing. We describe nine cases involving expression variants or new alleles. Three cases involved expression variants, including two null alleles and A*24020102L. One of the null alleles was a new variant of A*02. Seven cases involved new alleles. In five cases, there where discrepancies between HLA typing by serology and PCR-SSP. These included the three expression variants, one new B40 allele that typed serologically as B41 and one new B*07 allele that typed serologically as B42. Eight of these cases were found in the course of typing bone marrow transplant patients or potential unrelated donors since May of 2001 (total tested, 710 patients, 1914 donors). Thus, the incidence of null alleles was two in 2,624 (0.08%). Sequence-based typing (SBT) was performed on 676 of these samples. The decision to perform SBT was influenced by finding a serologic typing discrepancy in two cases. In one of those cases, SBT would probably have been performed at a later time, prior to final selection of a donor. Thus, the incidence of new alleles was between 4 and 6 of 676 (0.59-0.89%). We conclude that new HLA alleles and null alleles are uncommon but not extremely rare, and they continue to affect a significant number of unrelated donor searches.

PMID: 16029428