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Carefully calculated haplotype frequency sets are used in conjunction with probabilistic matching algorithms. They enable the calculation of match probabilities (shown as percentages) across donor phenotypes as well as individual loci when a search is performed in WMDA’s Search & Match Service.

With the last release of our the Search & Match Service, the WMDA has maintained a similar haplotype frequency set configuration as was used for Optimatch (Search & Match v1). In most cases the ION of the donor/cord blood unit will determine which haplotype frequency set is used.

To provide a more up-to-date representation of the donor pools worldwide, the haplotype frequency set calculations have been performed using the latest data in the WMDA Donor and CBU database. Calculations were performed using the open source algorithm Haplo-o-Mat (https://github.com/DKMS/Hapl-o-Mat and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450239/and applying it to high resolution donor typing results received from listing organisations to extrapolate the possible haplotypes of the region or organisation. Thus, an organisation or geographical region must meet a minimum threshold of both quantity and quality HLA typed records  to build usable and valuable frequencies. For cord blood units, we will use the same sets that were determined for the donor populations.

The inclusion criteria aims to balance the high number of donors, the quality of the HLA types and the complexity of the haplotype frequency estimation.

5-Locus haplotype frequency estimation was performed on all organisations/populations with at least 10 000 donors typed for HLA-A, -B, -C, -DRB1 and -DQB1 where ambiguity was low enough to be useful. Organisations in the same country that recruit from within the same population are usually combined, e.g. AT-ABMDR (ION-2614, Austrian Bone Marrow Donors) and AT-GFL (ION-4961, Verein Geben für Leben) but not for US-NMDP (general US population) and US-GOL (predominantly Ashkenazi Jews). 

A global frequency set was also calculated and will  be used for all patients and donors that, for some reason, do not match a typical haplotype frequency set. For example, when a registry is new and has not yet been assigned to an appropriate existing haplotype frequency set or when the from this registry deviate substantially enough from any typical haplotype frequency set that it does not make sense to assign them to an existing one. The number of this frequency set is 999. Information about which haplotype frequency set is applied to a donor search is provided in the search results API endpoint. 

Below, you can find information on how the haplotype frequency sets are assigned to the donors and cord blood units. The search service first determines if both registry ION and ethnicity of the donor or cord blood unit provided. Registry ION is then used to look up the country/region that the donor or cord blood unit belongs to. If yes, then it will check if an ethnicity specific set for this registry is assigned. If the donor, for example, is coming from USA and has ethnicity HISA, then we do not have a specific set available. However, there is a more broad Hispanic haplotype frequency set available (USA-HI) and will be used in this scenario.

If there is no ethnicity available for the donor or no ethnicity specific haplotype frequency set exists for that country, the system will check if a country specific haplotype frequency set is available or if the country is part of one of the regional haplotype frequency sets.

If no country specific haplotype frequency set is available, the Search & Match Service will use the global consensus haplotype frequency set.



Flowchart assigning a haplotype frequency (HF) set

In the table below, you can find the haplotype frequency set numbers and which countries/organisations were included as well as the total sample size. In the last part from the table we included regional sets, some country/ethnicity specific sets and the global consensus set.

The regional sets are defined as follows:

East Asia (eas): CN (CN+CN1), HK, TW, JP (Set number: 32)

Eastern Europe (eeu):AT (A+A2), CZ (CS+CS2), CY (CY+CY2), GR2, PL (PL3+PL5+PL6), TR (TRAN+TRIS+TRKK), BG, HU, HR, LT, MK, RU (R2+R4), RO, RS, SK, SI (Set number: 33)

South America (sam): AR, BR, UY (Set number: 34)





Input Data

Applied to:

HF set number

(pop_id)

Determination date

Sample size

ISO country code

ION

Search & Match Service_Registry_codes

IONs
12022-05226507AR5117

AR-INCUCAI

Same
22022-05149750AT

2614

4961

AT-ABMDR

AT-Verein

Same +

8162 - AT-Vita34 (CBB)

32022-0541348AU + NZ

7748

8261

AU-ABMDR

NZ-NZBMDR

Same
42022-0536351

BE

4201

BE-MDPB

Same
52022-0581859BR8766

BR-REDOME

Same
62022-0568077CA

5103

6912

CA-One Match

CA-HemaQuec

Same +

3066 - CA-VAR (CBB)

72022-05114900CH9341

CH-SBSC

Same
82022-05564150CN + HK + TW

2197

6681

4070

3458

CN-CMDP

CN-Sunshine

HK-HKBMDR

TW-TzuChi

Same +

1212 - TW-SinoCell (CBB)

1714 - TW-Meribank (CBB)

3105 - HK-CBB (CBB)

5812 - TW-StemCyte (CBB)

6459 - TW-Bionet (CBB)

6692 - TW-Healthbanks (CBB)

9281 - HK-Mononuclear (CBB)

92022-0574633CY

4278

9751

CY-Paraskevaidio

CY-CBMDR

Same
102022-0575810CZ

4753

5440

CZ-CSCR

CZ-CNMDR

Same
112022-052627544DE

5525

6939

DE-DKMS

DE-ZKRD

Same +

DE-DUS (CBB)

All ethnicities except for ASSW
122022-0553849DK

2015

7484

DK-DSCDW

DK-DSDE

Same
132022-0581265ES7813

ES-REDMO

Same
142022-0539567FI9738FI-FSCRSame
152022-0590069FR1804FR-FGMSame
162022-05636595GB + IE

6354

1726

2731

9968

5590

GB-Anthony

GB-WBMDR

GB-BBMR

GB-DKMS

IE-IUBMR

Same
172022-05102358GR

4979

GR-HTO

Same
182022-05651085IL

5239

4987

4068

IL-Hadassah

IL-Ezer Miz.

IL-SHBB

Same
192022-05530272IN

2824

4131

4460

8196

8486

9935

IN-GeneBand

IN-MDR

IN-ArjanVir

IN-ArjanVir

IN-Datri

IN-DKMS-BMST

Same
202022-0584477IT7450

IT-IBMDR

Same
212022-05328557NL8139

NL-Matchis

Same
222022-0516499NO7214

NO-NBMDR

Same
232022-051464544PL

3918

5391

7414

PL-ALF

PL-Poltranspl

PL-DKMS

Same
242022-0511029PT7358

PT-Cedace

Same
252022-0597139SA

1810

2107

SA-KFSHRC

SA-SSCDR

Same
262022-05184283SE5285

SE-Tobias

Same
272022-0578885SG3785

SG-BMDP

Same +

4291 - SG-SCBB (CBB)

282022-05122133TH8362

TH-TSCDR

Same
292022-05491941TR

3893

5509

3503

TR-TRAN

TR-TRIS

TR-TURKOK

Same
302022-051723292US3553

US-NMDP

3553 with ethnicities: 

  • None provided
  • MX
  • OT
  • UK

and the following organisations (all ethnicities)

4857 - US-CSCC (CBB)

6579 - US-Cleveland (CBB)

6738 - ZA-DKMS 

7470 - US-Lifebank

8118 - ZA-SABMR

8379 - US-StemCyte (CBB)

8691 - US-NCBP (CBB) 

312022-0597953US-GOL1033

US-GOL

Same
322022-05564561East Asia: CN+HK+TW+JP

1212

1714

2197

3105

3458

4070

5812

6459

6681

6692

6933


4364 - JP-JMDP

8405 - KR-KONOS

All other IONs that were used as input have their own country/region specific set. 

332022-052398213

Eastern Europe: AT+CZ+CY+GR+PL+TR+BG+HU+

HR+LT+MK+RU+RO+RS+SK+SI

1005
1372
1695
2073
2614
3503
3893
3918
4278
4307
4398
4565
4650
4753
4961
4979
5019
5391
5440
5509
5712
7197
7414
8162
8256
8714
9751
9778

1005
1372
4381
4398
4565
4650
5712
7197
8256
8714
9778
342022-05413438South America:
AR+BR+UY+CL+PY

1574

2547

5117

6517

8766

CL-DKMS

PY-VKS

AR-INCUCAI

UY-SINDOME

BR-REDOME

1574 - CL-DKMS

2547 - PY-VKS

4675 - CL-Vidacel (CBB)

6517 - UY-SINDOME

Brazil and Argentina have their own country-specific sets. 

352022-0538530ZA

6738

8118

ZA-DKMS

ZA-SABMR

None yet. Under investigation. 
362022-0535895IR

4993

6887

IR-INSCDN

IR-ISCDP

None yet. Under investigation. 
412022-0511012LU3099

LU-LMDP

Same
1002022-05151,204DE-ASSW

5525

6939

Subset of donors from these registries with ethnicity:

  • ASSW
Same
1012022-05656,591US-AF*3553

Subset of donors from this registry with ethnicities:

  • AF
  • AFNA
  • AFSS
Same
1022022-05796,780US-AS*3553

Subset of donors from this registry with ethnicities:

  • ASNE
  • AS
  • ASCE
  • ASOC
  • ASSE
  • ASSO
  • ASSW
Same
1032022-053,740,668US-CA*3553

Subset of donors from this registry with ethnicities:

  • CANA
  • CA
  • CAAU
  • CAER
  • CAEU
Same
1042022-051,002,893US-HI*3553

Subset of donors from this registry with ethnicities:

  • HISA
  • HI
  • HICA
Same
9992022-0511,430,561

All donorsAll donors/ CBUs not specifically matching any other set. 

In order for WMDA to perform these calculations on behalf of member organisations, it is important for organisations to submit donor ethnicity data and high resolution typing when available. This greatly improves the haplotype frequency sets and allows for individual donor match grades to be more accurate. 

NOTE: None of the Japanese and Korean donors have been typed for DQB1. This means that no Japanese or Korean donors were included in the calculations for set #32. Therefore, the haplotype frequency set applied to Japanese and Korean donors is likely to be biased against Japanese and Korean . We have kindly received a self-generated haplotype frequency set from the Japanese registry and are working on integrating it in the updated Search & Match Service. Whether to apply the provided Japanese haplotype frequency set or to apply set #32 is still under investigation. 

NOTE: in some cases, a country’s donors may be used in a national haplotype frequency set as well as a regional one. For example, Austrian donors are used in their own set (#2) as well as the Eastern Europe regional set (#33). When calculating match probabilities, the most specific set is always used. So for donors from Austrian Bone Marrow Donor Registry or Verein Geben für Leben set #2 is used, but for Slovakian donors there were not enough donors typed at high resolution to calculate their own set and so the regional set is assigned (#33). 

There are also countries or donors with a specific ethnic background in a country for which there was no specific haplotype frequency set in Optimas, but for which there are now enough donors for their own haplotype frequency set and/or their haplotype. We are currently investigating whether it would provide benefit to host these separately. These include: 

  • IN-DATRI: Since DATRI is recruiting in a specific region of India, its haplotype frequencies may be significantly different from the haplotype frequencies found throughout the greater India (set #19).
  • ZA: There are enough donors from South Africa typed at high resolution to merit its own set. Considering the unique heritage of South African donors, having frequency sets per ethnic group would be especially beneficial.
It is important to know that the haplotype frequency assigned to your organisation can be changed!

You can request that your donors be returned to the global consensus haplotype frequency set or to a regional set. Your request should include the reasons why you believe that another set is more applicable for your donors. Additionally, if your organisation has a frequency set available that you would like to see utilized for the donors of your organisation, we can implement it as well. In this case, your request should include at least a description about your population, the sample size, inclusion and exclusion criteria, calculation method, and the reasons why your haplotype frequency set would be better than the current set applied by WMDA. Both requests will be reviewed by the WMDA Bioinformatics & Innovation Working Group. Please send requests to support@wmda.info.


DateVersionDescriptionAuthor
2017-10-311.0Replacement BMDW global haplotype frequency set for more specific setsJK
2018-01-241.1Modification some sets; introduced during OptiMatch version 3.31.0JK
2019-02-151.2Replaced BMDW by WMDA / Search & Match Service; updated email addressJK
2022-08-151.3Copied original page and updated with relevant info for HAP-E algorithm. MM
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