As a pioneer in HLA sequence based typing, we have provided millions of cost-effective HLA SBT for donor registries, pharmacogenomics, donor centers, cord blood typing, transplant centers, and HLA laboratories.
HistoGenetics is applying cutting-edge sequencing technologies to study all living species, helping lead innovation in human, plant, and animal research and precision medicine.
Our pioneering work since our founding has led to SBT becoming the standard for HLA typing, making other methods obsolete for high-resolution HLA typing in donor recruitment and patient matching for blood stem cell transplantation since 2006.
Our proprietary process provides a full suite of tissue-typing and genomic services with the highest level of quality assurance and accelerated turnaround times. By introducing SMRT sequencing for routine HLA testing for whole gene Class I and Long Range Class II, HistoGenetics set the new Gold Standard.
HistoGenetics is currently applying advances in genomic technologies such as the PacBio Sequel and BioNano Saphyr platforms for analysis of Whole Genome by Sequencing and Optical Mapping, respectively. This will enable us to determine the complex genetic regions and structural variations that could be the basis for health and diseases. This new information will lay the foundation for Precision Medicine.
Learn about our services
Dr. Soo Young Yang
Chairman and Founder
Download CVDr. Yang pioneered development of biochemical and molecular typing methods for HLA at the Biochemical and Molecular Immunogenetics Laboratory at Memorial Sloan-Kettering Cancer Center. With over 35 years of extensive research and experience in HLA genetics, Dr. Yang has created invaluable reagents and informatics for biochemical and molecular typing of HLA that have contributed significantly to the field of human immunogenetics. This internationally recognized expertise forms the foundation of HistoGenetics advanced technologies and services.
Dr. Nezih Cereb
CEO and Co-Founder
Download CVDr. Cereb has been a long time associate of Dr. Yang, with whom he has played a key role in elucidating the HLA-Class 1 intron sequences that made HLA class 1 DNA typing feasible. Dr. Cereb is an expert in introducing, integrating and implementing diverse technologies for HLA typing and has made high volume, high throughput and high resolution HLA-SBT a reality. His proven abilities stem from a diverse background in clinical medicine, particularly bone marrow transplantation and basic and applied immunogenetics research.
Using state-of-the-art reagents, software, and facilities, we provide a full suite of tissue-typing services with the highest level of quality assurance and accelerated turnaround times.
We provide high-quality, cost-effective typing for:
- HLA -A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1
- HLA -E, -G
- MICA, MICB,DRA
- KIR Gene Content Typing on Illumina platform
- KIR 3DL1, 3DS1 Gene Allele level typing on PacBio platform
- FCGR (!)
Gene Name Variant (SNP ID) FcgR2A rs1801274 FcgR3A rs396991 FcgR2C rs114945036, rs138747765, rs78603008, rs759550223, rs373013207, rs76277413, rs149754834 FcgR3B rs2290834, rs200688856, rs527909462, rs448740, rs5030738, rs147574249 - Molecular ABO Rh typing (!)
Our Molecular testing for ABO Rh serotype prediction is based on an algorithm that we developed for known Serotype of 1000 Caucasian individuals using ABO Exon 2, Exon 6 & Exon 7 and RH Exon 4, Exon 5, Exon 7 and Exon 9 sequence motifs determined by NGS. We had 100% concordance in that study. Our algorithm was further validated with several thousands of other samples.
There could be variations outside of the regions that we are sequencing that could cause changes to ABO and Rh – serotype.Occasionally we see discrepancy between the serotype and our prediction based on NGS, especially in non-Caucasian individuals.
However, the serology reagents that are developed for Caucasian individuals may also have discrepant results in non-Caucasian individuals.Therefore ABO/RhD typing by molecular methods is to be used only for the purpose of presumptively listing the predicted ABO/RhD phenotype on the Registry.
The Registry listing of ABO/Rh may only be used as a predictive value and may not be used as one of two required tests performed by an FDA or CMS approved method.
Our Laboratory policy states that ABO/RhD typing by molecular methods must not be used for clinical purposes. - CCR5 Δ 32 detection
- HPA-1a / HPA-1b Human Platelet Antigen Genotyping
- CMV IgG detection in buccal swabs
- T Cell Receptor (TCR) Repertoire analysis by NGS
- Hemoglobin Beta Gene sequencing
- Monitoring engraftment
- Whole Genome sequencing on PacBio Sequel platform
- Whole Genome optical mapping on BioNano Saphyr platform
- Our Molecular testing for ABO Rh serotype prediction is based on an algorithm that we developed for known Serotype of 1000 Caucasian individuals using ABO Exon 2, Exon 6 & Exon 7 and RH Exon 4, Exon 5, Exon 7 and Exon 9 sequence motifs determined by NGS. We had 100% concordance in that study. Our algorithm was further validated with several thousands of other samples. There could be variations outside of the regions that we are sequencing that could cause changes to ABO and Rh – serotype.
Occasionally we see discrepancy between the serotype and our prediction based on NGS, especially in non-Caucasian individuals. However, the serology reagents that are developed for Caucasian individuals may also have discrepant results in non-Caucasian individuals.
Therefore ABO/RhD typing by molecular methods is to be used only for the purpose of presumptively listing the predicted ABO/RhD phenotype on the Registry. The Registry listing of ABO/Rh may only be used as a predictive value and may not be used as one of two required tests performed by an FDA or CMS approved method. Our Laboratory policy states that ABO/RhD typing by molecular methods must not be used for clinical purposes.
Our High Resolution Typing levels and classes:
- 1x High Resolution Typing
- Class I: Antigen Recognition Site (ARS) Typing for exon 2 and 3 in phase
- Class II: ARS Typing for exon 2
- 2x High Resolution Typing
- Class I: Exon 2, 3 and 4 typing
- Class II: Exon 2 and 3 typing
- 3x High Resolution Typing
- Class I: Exon 2, 3 and 4 typing, and ruling out CWD null alleles
- Class II: Exon 2 and 3 typing
- 4x High Resolution Typing
- Class I: Exons 1-8 typing
- Class II: Exons 2-6 typing
- 8x High Resolution Typing
- Class I: All exons and introns typing
- Class II: Exons 2-6 and introns 2-5 typing
Levels of HLA High Resolution Typing Under NGS Microscope
-
Class I
— Antigen Recognition Site (ARS) Typing for Exon 2 and 3 in phase: — Exon 2, 3 and 4 typing: — Exon 2, 3 and 4 typing, and ruling out CWD null alleles: — Exons 1-8 typing: — All exons and introns typing:
- Exon 1
- Exon 2
- Exon 3
- Exon 4
- Exon 5
- Exon 6
- Exon 7
- Exon 8
- Exon 1
- Exon 2
- Exon 3
- Exon 4
- Exon 5
- Exon 6
- Exon 7
- Exon 8
- ↑ Introns
- ↑ CWD Null
- ↑ ARS Typing
- ↑ ARS Typing
- ↑ CWD Null
- ↑ CWD Null
- ↑ CWD Null
-
Class II
— Antigen Recognition Site (ARS) Typing for Exon 2: — Exon 2 and 3 typing: — Exon 2 and 3 typing: — Exons 2-6 typing: — Exons 2-6 and introns 2-5 typing:
- Exon 1
- Exon 2
- Exon 3
- Exon 4
- Exon 5
- Exon 6
- Exon 1
- Exon 2
- //
- Exon 3
- //
- Exon 4
- Exon 5
- //
- Exon 6
Reporting turnaround time
- 3 days for ultra urgent clinical samples (in working days)
- 5 days for urgent clinical samples (in working days)
- 8 days for standard clinical samples (in working days)
- 21 days for registry/research typing samples (in calendar days)
- 28 days for registry / research typing samples (in calendar days)
- TAT can be tailored for client requirements. Please use the quote form below and specify your requirements.
Illumina MiSeq
Illumina NovaSeq
PacBio Revio
PacBio Sequel
Oxford Nanopore
BioNano SaphyrOur main sequencing platforms are Next Generation Sequencing (NGS) technology using Illumina MiSeq, Novaseq and 3rd generation sequencing technology with Pacific Biosciences using Sequel and Revio and Oxford NANOPORE Technologies GridION and P2 Solo platforms. We have the largest fleet of Sequel II and Sequel IIe and Sequel I.
We use SMRT sequencing for routine HLA testing for whole gene Class I and Long Range Class II. We resolve ambiguities that are not resolved using the Illumina approach and further characterize novel alleles using SMRT sequencing.
Certificate Information
Frequently Asked Questions
HLA molecules provides immunological unique identification to humans that modulates immune response with external and internal variables. Learn more about HLA here: http://en.wikipedia.org/wiki/Human_leukocyte_antigen
External variables are infectious agents (viruses, bacteria, fungi, parasites), food, foreign tissue, drugs and etc. Internal factors are tissue modification due to infections, cancer and physical trauma (heat, cold etc). Learn more here: http://en.wikipedia.org/wiki/Antigen_presentation
In the 1950s it was shown that organ and tissue transplantation could offer a cure for numerous illnesses. But the success of these procedures depends to the matching degree between the patient and their donor for HLA.
The regions of HLA proteins that interact with T-cell receptors polypeptides (proteins) are extremely variable from individual to individual (polymorphic), and they are called Antigen Recognition Sites (ARS). The polymorphism is conferred by DNA sequences that encode those polypeptides (proteins). In Class I molecules (HLA-A, -B, -C) exon 2 and 3 of Class I genes encodes for those polypeptides and they are called ARS exons. In Class II molecules (HLA-DRB1, -DQB1 and DPB1) exon 2 of class II genes encodes the ARS regions.
ARS T Cell receptor interaction is shown below:
Therefore in HLA testing we primarily sequence those exons and predict the protein sequences (1x High Resolution). DNA sequences that result in identical protein sequences for ARS regions are considered a match.
Some clinicians would like to test to see if it is possible to match for alpha-3 domain of HLA proteins. Exon 4 and Exon 3 of Class I and Class II genes encode alpha-3 polypeptides, respectively (2x high resolution). If alpha-3 regions are not matching but ARS regions match, if that donor is the best available donor otherwise, he/she could be selected for blood stem cell donation.
Some irregularities in DNA sequences may result in no expression or expression of totally non-functional protein. Those irregularities could be missing base(s) (deletions), have extra base(s) (insertions), or have base substitutions that result in premature termination of HLA protein synthesis (early stop codons). In certain cases those irregularities could happen in regions of the genes that are outside of the ARS regions. Therefore by just testing for ARS DNA sequences, one may miss those null alleles. This could result in calling a mismatch typing as a match and could affect the success of the transplant outcome.
Those null alleles that have seen at least five times in different ethnic populations are tested in donors and patients. We call this extra test as testing for CWD null alleles. (3x High resolution).
Now with advances of Next Generation Sequencing (NGS) technologies, especially of Illumina and Pacific Biosciences we can sequence all exons of class I (7 Exons HLA-B, 8 exons HLA-A and HLA-C) and Class II (4x High Resolution). When requested we can also provide the sequences of non-coding region between the exons, introns, along with the exon sequences (8x High Resolution).
HistoGenetics provides a suite of tissue-typing services with the highest level of quality assurance and accelerated turnaround times. Our prices are competitive and we can handle any volume.
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