Long-Read Sequencing

Comprehensive Analysis of Thalassemia Alleles (CATSA)

The World’s First IVD-Certified LRS Solution for Thalassemia

The Challenges of Thalassemia Detection

Due to the high complexity of the globin gene clusters, no single conventional test can detect the full spectrum of thalassemia and hemoglobinopathy variants. Current methods (PCR and short-read NGS) often fail to identify structural variants and rare mutations. This leads to expensive step-wise testing, missed carriers, and genetically unresolved cases.

Limitations of Conventional Test

Hematological Screening (CBC/CE)

Lacks sensitivity for carriers
Frequently misses silent carriers of α⁺-thalassemia, β⁺-thalassemia, and α-triplications

PCR-based Test

Limited to hotspot variants
While over a thousand of thalassemia variants exist, most PCR panels only cover a few dozen common mutations

Short-read NGS

Struggles with the high homology between HBA1 and HBA2, HBB and HBD
Often misses large structural variants, miscalls variants, and cannot provide phasing information

The Ultimate Thalassemia Clinical Solution

Comprehensive Analysis of Thalassemia Alleles (CATSA) resolves the limitations of routine testing. Powered by advanced PacBio SMRT Sequencing, CATSA consolidates fragmented testing into a single, efficient workflow with low failure rates.

Reliably detects >2,200 known variants for thalassemia and hemoglobinopathies
Accurately identifies rare variants and SVs
Delivers accurate results for diverse populations, making it the new standard for carrier screening

Expert consensus officially endorsed as a diagnostic and screening tool by the Medical Genetics Branch of the Chinese Medical Doctor Association (2025)¹

Comparison: CATSA vs. PCR and NGS

Variants

PCR Methods

NGS

CATSA

Common Deletions

✔

Other Deletions

✔

(Struggle if inside homology)

✔

Homologous Recombination

(e.g. α-triplicate)

(Some may be misinterpreted as deletions)

✔

Common SNVs/InDels

✔

(Susceptible to homology)

✔

Other SNVs/InDels

✔

Phasing

✔

Performance backed by published data

Backed by over 50 peer-reviewed publications, CATSA consistently demonstrates superior accuracy and clinical utility in real-world scenarios.

20+ novel variants identified
100% accuracy²

A total of 1,759 blood samples with abnormal hemoglobin parameters were collected across 10 centers to compare CATSA with a standard PCR panel²

Compare with NGS

CATSA has 100% accuracy compared to NGS miscalls in both HBA1/2 and HBB genes, driving a 2.28% improvement in overall detection yield

NGS (full-length HBA1/2 and HBB) and CATSA were simultaneously performed for 1,122 individuals in Hainan Province³

Versus a 13.7% NGS error rate (missed triplications and HKαα miscalls as deletions), CATSA delivered 100% accuracy across all α-thalassemia carriers

A total of 2,926 participants were retrospectively enrolled in Shanghai for carrier screening of 5 diseases using both commercial NGS carrier screening panel and LRS panels, with CATSA applied for thalassemia⁴

Prenatal Case Study - compare with PCR

In a multi-center retrospective study of 278 at-risk amniotic fluid samples, CATSA:

Outperformed PCR panel by corrected the results in 15 samples (5.4%)
Reclassified the predicted phenotype severity in 8 fetuses (2 cases from Trait to Intermedia, and 1 from Intermedia to Trait).

These insights directly influenced pregnancy management and counseling.⁵

Comprehensive coverage

Covers the most types of thalassemia and hemoglobinopathy variants

The new gold standard

Improves detection rate compared with routine test with >99.9% accuracy

Proven at scale

With 350,000+ cases and 50+ publications

When considering our send-out sequencing services:

Consultation: Contact our team for the most current test specifications.
Sample Preparation: Check sample types and shipment requirements to ensure high-quality results. Please check your local export regulations and logistics partners.
Submission: Contact Xcelom when placing an order. Include the completed Test Request and Consent Form, along with any required documents.

Sample Requirements

Peripheral Blood: 2 mL in EDTA tube

Dried Blood Spot (DBS): 3 spots, ≥ 8mm diameter each

Long-fragment gDNA

'**For prenatal cases, please include maternal sample for STR to exclude maternal contamination.

Transport Conditions

2-8℃, arrive within 72 hours

Testing Scope

637 Panel

Covers 637 variants associated with α-/β-thalassemia, and hemoglobinopathies (including sickle cell anemia), including:

HBA1/2 : 30 deletions, 4 homologous recombination, and 219 SNVs/InDels
HBB: 28 deletions, and 356 SNVs/InDels

Expanded Panel

Covers 2025 variants associated with α-/β-thalassemia, hemoglobinopathies, and hemoglobin variants, including:

HBA1/2 : 30 deletions, 4 homologous recombination, and 929 SNVs/InDels
HBB: 28 deletions, and 1034 SNVs/InDels

Comprehensive Panel

Covers variants associated with α-/β-thalassemia, hemoglobinopathies, and hemoglobin variants in HBA1/2, HBB, and HBD, including low-frequency mutations and uncertain significance associated with thalassemia and hemoglobinopathy

Turnaround Time (TAT)

15 working days

Xcelom Limited and Berry Genomics provide an end-to-end turnkey solution for labs wishing to conduct this test in-house.

Laboratory Setup: Full consultation
Workflow Integration: SOPs, IVD/RUO reagents, and staff training
Bioinformatics: Complete IVD/RUO software suite for sample management and automated report generation

Platform

PacBio Sequel IIe, Vega and Revio system

Sample Type

gDNA from dried blood spot, blood, buccal swab, and amniotic fluid

Test per Batch

Max. 384 Tests per SMRT Cell (Mixed Batching Supported)

Operation Time

~ 77 hours (Hand on time: ~10.5 hours)

Automation

Supported

Coverage

Targets full-length of HBA1/2, HBB-HBD, and HS-40 regions

Covers > 2,200 clinically relevant variants

The provided time is based on the PacBio Sequel IIe system and may vary across different labs and systems.

Resources

CATSA Brochure

CATSA Scientific Poster

References:

1. Consortium For The Application Of Single-Molecule Real-Time Sequencing For The Precision Medicine And Control Of Thalassemia, Group Of Clinical Genetics Medical Genetics Branch Of Chinese Medical Doctor Association, Wu L. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025;42(4):385-396.

2. Liang Q, Gu W, Chen P, et al. A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA). J Mol Diagn. 2021;23(9):1195-1204.

3. Huang R, Liu Y, Xu J, et al. Back-to-Back Comparison of Third-Generation Sequencing and Next-Generation Sequencing in Carrier Screening of Thalassemia. Arch Pathol Lab Med. 2024;148(7):797-804.

4. Li S, Hua R, Han X, et al. Targeted long-read sequencing facilitates effective carrier screening for complex monogenic diseases including spinal muscular atrophy, α-/β-thalassemia, 21-hydroxylase deficiency, and fragile-X syndrome. J Transl Med. 2025;23(1):307.

5. Liang Q, He J, Li Q, et al. Evaluating the Clinical Utility of a Long-Read Sequencing-Based Approach in Prenatal Diagnosis of Thalassemia. Clin Chem. 2023;69(3):239-250.