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Using HLAMatchMaker: Maternal-Fetal Incompatibility and the Risk of Disease

Using HLAMatchMaker: Maternal-Fetal Incompatibility and the Risk of Disease. Miguel Angel Gonzalez Mentor: Janet Sinsheimer, UCLA Hsinju Hsieh, UCLA. Outline. Introduction HLAMatchMaker Results Conclusions. HLA Incompatibility. Human Leukocyte Antigen

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Using HLAMatchMaker: Maternal-Fetal Incompatibility and the Risk of Disease

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  1. Using HLAMatchMaker:Maternal-Fetal Incompatibility and the Risk of Disease Miguel Angel Gonzalez Mentor: Janet Sinsheimer, UCLA Hsinju Hsieh, UCLA

  2. Outline • Introduction • HLAMatchMaker • Results • Conclusions

  3. HLA Incompatibility • Human Leukocyte Antigen • Presence of structures on cells that are sites for antibody binding • Problems • Mother and fetus closely matched • Fetus does not set up correct immunological barrier

  4. Experimental Data • Family Studies • Mother, father, and at least 1 child with schizophrenia • HLA-A, B, & DRB1 types were determined • Study focuses on mother-fetus relationship

  5. Current Studies • WHO • Current method for HLA comparison • Biological comparison using serum screening • Match = 1 • Mismatch = 0 Chris O’Callaghan – University of Oxford http://neelix.molbiol.ox.ac.uk:8080/userweb/cocallag/

  6. Hypothesis • Incompatibility between the mother and fetus with respect to HLA can be a risk factor for neurological diseases such as schizophrenia. • Also, to quantify the level of mismatching and to determine how sensible the WHO method is.

  7. HLAMatchMaker • Written by Rene J. Duquesnoy, Ph.D. • Computer algorithm for identifying acceptable HLA mismatches for patients without the need for extensive serum screening

  8. HLAMatchMaker • Purpose: to identify the best candidates for organ transplantation • Compares the amino acid sequences of HLA antigens.

  9. Internship Goal • To adapt HLAMatchMaker to the studies of the Sinsheimer lab. • Use HLAMatchMaker to identify differences in the amino acid sequences of mother and fetus HLA. • Compare to the current analysis: WHO vs HLAMatchMaker • To determine mismatch severity

  10. HLAMatchMaker Results Child Mother

  11. A*23 107G 142I 144tQr 149aAr 151aRv 166Dg A*02 107W 142T 144tKh 149aAh 151aHv 166Ew Visual Comparison

  12. HLAMatchMaker WHO Comparison • Using an excel macro (efficient), large sets of data can be analyzed. • To make comparable to WHO, Match = 1 Mismatch = 0 • Results used to construct a comparison table (Pivot Table).

  13. Pivot Table HLAMatchMaker

  14. Conclusion • Goal Achieved • Using excel macros it was possible to adapt HLAMatchMaker to the Sinsheimer lab studies. • Results showed no difference between WHO and HLAMatchMaker • HLAMatchMaker results can be used to support WHO findings

  15. Future Studies • Determine the severity of mismatching • Differences in amino acids

  16. Acknowledgements • Dr. Janet Sinsheimer, UCLA • Dr. Christina Palmer, UCLA • Hsinju Hsieh, UCLA • Funding • NIH • NIMH • SoCalBSI

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