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PubMed2005

Desperately seeking donors: the 'saviour sibling' decision in Quintavalle v Human Fertilisation and Embryology Authority (UK).

The recent House of Lords decision in Quintavalle v Human Fertilisation and Embryology Authority has raised difficult and complex issues regarding the extent to which embryo selection and reproductive technology can be used as a means of rectifying genetic disorders and treating critically ill children. This comment outlines the facts of Quintavalle and explores how the House of Lords approached the legal, ethical and policy issues that arose out of the Human Fertilisation and Embryology Authority's (UK) decision to allow reproductive and embryo technology to be used to produce a 'saviour sibling' whose tissue could be used to save the life of a critically ill child. Particular attention will be given to the implications of the decision in Quintavalle for Australian family and medical law and policy. As part of this focus, the comment explores the current Australian legislative and policy framework regarding the use of genetic and reproductive technology as a mechanism through which to assist critically ill siblings. It is argued that the present Australian framework would appear to impose significant limits on the medical uses of genetic technology and, in this context, would seem to reflect many of the principles that were articulated by the House of Lords in Quintavalle.

Australia↗
PubMed1991

Effect of mismatches for major histocompatibility complex and minor antigens on corneal graft rejection.

The importance of minor histocompatibility genes in corneal graft rejection was investigated using a model that simulates the major histocompatibility complex (MHC) and minor mismatches of the human allograft more accurately than previous animal models. DA(RT1a) x LEW(RT1(1]F1 hybrid rats were backcrossed to LEW, and the backcross generation were used as corneal graft recipients. Female DA(RT1a) strain animals were used as donors throughout. As in humans, the MHC disparity (a to 1) between each donor-recipient pair could be controlled; minor mismatches were variable and unknown. The MHC haplotype of each backcross individual (either homozygous l/l) or heterozygous a/l) was determined. Depending on this haplotype, the transplanted DA cornea was either matched or mismatched with the recipient for MHC antigens. The average proportion of minor disparate loci was 50%, although this was variable and unknown from recipient to recipient. Some animals of each MHC type were sensitized with three subcutaneous DA strain skin grafts at intervals of 2 weeks. Prior sensitization caused more rapid corneal graft rejection in both MHC mismatched (P less than 0.001) and matched (P less than 0.01) animals. All animals in the two MHC-mismatched groups (sensitized, 26; unsensitized, 17) and most in the MHC-matched groups (sensitized, 25 of 27; unsensitized, all 13) rejected their grafts. The MHC matching resulted in a greater range of survival times, although the difference in survival in unsensitized animals between matched and mismatched groups was not significant (unsensitized, P greater than 0.05; sensitized, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Current approach to HLA typing for bone marrow transplantation: oligonucleotide typing by hybridization on DNA amplified by polymerase chain reaction].

The extensive polymorphism of major histocompatibility complex HLA class II antigens plays a crucial role in transplantation immunology. The molecular biology of the HLA-D region has revealed that the polymorphism at the HLA-DR, -DQ and -DP loci is much greater than was expected from serology, and thus requires accurate typing technology. We have shown that HLA class II polymorphism can be analyzed directly at the DNA level by hybridization with locus- and allele-specific oligonucleotide probes (oligotyping) derived from the variable first domain exon sequences of DR, DQ and DP genes. The same HLA typing procedure can be performed by direct hybridization on DNA previously amplified by the polymerase chain reaction (PCR). Here we show that oligotyping can complement and/or replace serological as well as cellular (Dw) typing and serves to predict a positive mixed lymphocyte culture. It is now operational (a) to replace serology when class II expression is absent or aberrant (e.g. leukemic patients, class II deficiencies) and (b) to improve, by the analysis of HLA-DR and -DQ micropolymorphism, the speed and reliability of the selection of optimally-matched unrelated donors for bone marrow transplantation.

Bone Marrow Transplantation↗