Abstract

There are now many molecular biological techniques available to define HLA class I and class II alleles. Some of these are also applicable to other human polymorphic genes, in particular to those non-HLA genes encoded within the Mhc. The range of techniques available allows laboratories to choose those most suited to their purpose. The routine laboratory supporting solid organ transplants will need to type large numbers of potential recipients over a period of time, probably using PCR-SSOP while donors will be typed singly and rapidly using PCR-SSP with HLA allele compatibility determined by heteroduplex analysis. Laboratories supporting bone marrow transplantation, where time is less pressing, can choose from the whole range of techniques to determine accurately donor recipient Mhc compatibility. For disease studies, techniques defining precise HLA allele sequence polymorphisms are needed and high sample numbers have to be accommodated. When an association is established allele sequencing has to be used. In the near future, the precise role of HLA alleles in transplantation and disease susceptibility is likely to be established unambiguously.

Highlights

  • The human major histocompatibility complex (Mhc) codes for the HLA genes which are the most polymorphic known in man

  • Our understanding of this genetic region has grown exponentially over a relatively short period of time. This is largely due to the world-wide collaborative efforts of immunogeneticists and transplantation biologists in organising International Histocompatibility Workshops (IHWs)

  • The molecular techniques employed in HLA allele typing began with the detection of linked restriction fragment length polymorphisms (RFLPs) to identify HLA-DR specificities at the gene sequence level

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Summary

SUMMARY

There are many molecular biological techniques available to define HLA class I and class II alleles. Some of these are applicable to other human polymorphic genes, in particular to those non-HLA genes encoded within the Mhc. The range of techniques available allows laboratories to choose those most suited to their purpose. The routine laboratory supporting solid organ transplants will need to type large numbers of potential recipients over a period of time, probably using PCR-SSOP while donors will be typed singly and rapidly using PCR-SSP with HLA allele compatibility determined by heteroduplex analysis. Techniques defining precise HLA allele sequence polymorphisms are needed and high sample numbers have to be accommodated. The precise role of HLA alleles in transplantation and disease susceptibility is likely to be established unambiguously

INTRODUCTION
OVERVIEW OF TECHNIQUES
METHOD RESOLUTION
DNA sequencing based typing
Carboxylated wells primary am ine
IMPACT OF HLA ALLELE TYPING ON DISEASE STUDIES
APPLICAnONS TO ORGAN TRANSPLANTAnON
Findings
ACKNOW LEDGEMENTS
Full Text
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