1. Royal Liverpool University Hospital & University of Liverpool
ALLELE FREQUENCIES.NET DATABASE
(AFND)
TO SUPPORT H&I
Derek Middleton
Royal Liverpool University Hospital & University of Liverpool

2. DATABASE POPULATIONS 1/5/2016
Polymorphic Region
Population Studies
Gene/Allele Data
Haplotype Data
Genotype Data
HLA
1050
1035
426 -
KIR
238
237
154
Cytokine
121
MIC 62 21
Totals
1,471
1,455
447

6. 1 2

8. 1 2

14. IMGT/HLA alleles
7,527 alleles
Release April 2012

16. RARE ALLELE SEARCH

17. INFORMATION PROVIDED BY INDIVIDUAL LAB ON RARE ALLELE

18. HISTOGRAMS OF FINDING OF HLA ALLELES

19. Rare HLA alleles detector (RHAD)

20. Study of Rare & Novel HLA Alleles by NGS HLA.
Study of Rare & Novel HLA Alleles by NGS HLA
Non-CWD based on Mack et al
to confirm and further characterize these alleles in multiple populations and when possible determine their haplotype association.
The subjects and families should be previously HLA typed at any level (serology, DNA).
Investigators may submit
Samples
NGS data
Family members

21. KIR GENE, ALLELE FREQUENCIES

23. KIR GENOTYPES

24. GENOTYPES FOUND IN ONLY ONE POPULATION (n=166)
Number of Pops
Number of Genotypes 1 12 2 11 9 7 3 6 5 4 20
150 genotypes found in only 1 individual genotype in 4 individuals
12 genotypes in 2 individuals genotype in 5 individuals
2 genotype in 3 individuals

26. KDDB query page

27. KDDB query page

28. CRITERIA FOR DEFINING GOLD,SILVER,BRONZE DATASETS
Gold standard
Silver standard
Bronze standard
Allele frequency
Allele frequencies sum to 1 (± 0.015) 
Allele frequencies sum to 1 (± 0.015)
Any that do not match to gold and silver criteria
Allele name resolution
All allele names are at least two fields long.
Allele name lengths are mixed between one field and two or more fields long.
Sample size
≥50 individuals
Any

30. Number of alleles, datasets and individuals (by 10x4) by loci in Gold standard datasets.

32. STANDARDISED Reporting of Genotyping Results
The HLA community focuses on allele names, often to the exclusion of the primary data.
No/little information is available about intron/exons interrogated, primer sequences, or informatics.
Reference database versioning is poorly documented. An HLA genotype that represented a unique diploid sequence under one database release might represent multiple diploid sequences in later releases, as new polymorphism is identified in other regions of the gene.
The result is that genotyping results are static, and cannot easily be re-evaluated in the context of reference database updates. The equivalence of genotyping results generated using different references or different platforms cannot easily be determined.
We’re left throwing out a lot of data

33. HUMAN IMMUNOLOGY/AFND
Short Population Reports: HLA; KIR; MIC; Cytokine Demographic information Typing methods/Kits; alleles able to be detected Raw/individual ambiguous genotype data Data after ambiguity resolution (and how) Analysis H-W; allele frequencies; estimation of haplotype frequencies

34. CHECKING OF DATA Data automatically checked for errors:
correct nomenclature
reported ambiguities resolved
frequencies reported complete and consistent with data
Tool will immediately highlight to the User any problems
Once validated, one click to send data to AFND

39.
Look at donor registries - practical

41. HLA−A and −B Epitope Frequencies in World Populations
Epitope Frequencies were obtained from raw genotyping data

43. Human Immunology, 2016, 77, Issue 3
Special Issue: Histocompatibility and Immunogenetics Data Resources
Allele Frequencies Net Database:
Improvements for storage of individual
genotypes and analysis of existing data
238-48
ACKNOWLEDGEMENTS
Eduardo dos Santos, Tony McCabe, Andy Jones, James Jones
Faviel F. Gonzalez-Galarza
Steve Mack, Alicia Sanchez-Mazas