HLA Haplotype Frequency Analysis Within India: Pre-Requisite For Bone Marrow Donor Registry and Cord Blood Bank Planning

To better plan recruitment of volunteer adult unrelated donors for a registry and umbilical cord blood donations for cord banks to supply grafts for hematopoietic cell transplantation to serve Indian transplant candidate patients, we analyzed existing HLA typing data to estimate Indian national and regional populations’ HLA haplotype frequencies.

Indian BMT centers, renal transplant centers, adult donor registries and cord blood banks collaborated to collect HLA typing and demographic data.  We have produced a catalogue of the frequency, and regional diversity, of HLA haplotypes in the Indian population. Haplotype frequency analysis was performed on the registry datasets (N=26,239) using a maximum-likelihood method capable of providing high-resolution estimates from typing data with ambiguities.  These frequencies were generated for 20 regional subgroups into cohorts defined by either geographic state or by native language; and the 14 largest groups were used to develop a computational model of match rates.  Patient family typing data was used to set phase for a group of N=485 patients that was used to run searches against the NMDP registry.

The match rates for Indian patients searching the NMDP USA database (over 11 million donors including DKMS) were 39.7% at the 8/8 allele level (A, B, C, DRB1 high-resolution) and 92.2% at the 7/8 level.  Matching models for patients (averaged across the 14 regional subgroups) showed a match rate within India at the current registry sizes of 13.7% at the 8/8 level and 38.2% at the 7/8 level.  Increasing the registry to 1,000,000 would raise this to 55.0% for 8/8 and 84.1% for 7/8.  A cord blood inventory of 50,000 units would provide a match rate of 22.2% at the 6/6 level and 78.9% at the 5/6 level.  Increasing to a cord blood inventory of 250,000 units would increase these match rates to 42.5% at the 6/6 level and 90.3% at the 5/6 level.

These data will define the needs and serve as critical planning data to define and direct donor recruitment goals to establish an effective Donor Registry and cord blood banking facilities able to serve the needs of Indian patients who could benefit from the curative potential of transplantation. Developed data will be shared with the broader scientific community to facilitate future studies of HLA in areas such as disease association, anthropology and transplantation.