National Genomic Data-Sharing Framework for Inherited Hematological Disorders in Pakistan  

Background

Genomic testing for inherited hematological disorders is increasingly performed in Pakistan, including testing for hemoglobinopathies, inherited bone marrow failure syndromes, hereditary anemias, and other rare disorders. However, genomic data generated across hospitals, diagnostic laboratories, and research institutions remain largely fragmented, with no established national mechanism for interoperable discovery and sharing.

This limits collaborative variant interpretation, reduces the availability of population-specific genomic evidence, and creates missed opportunities for multicenter research and improved diagnosis. The challenge is compounded by limited access to bioinformatics expertise and the absence of established technical and governance frameworks for responsible genomic data sharing.

This project will use inherited hematological disorders as a practical use case to develop and demonstrate a National Genomic Data-Sharing Framework for Pakistan. The project will begin with a proof of concept using synthetic data between the Armed Forces Bone Marrow Transplant Centre and Children’s Hospital Lahore, allowing technical and governance workflows to be tested safely. It will then progress to appropriately governed real-world genomic data before scaling to additional institutions.

The framework will explore implementation of relevant GA4GH standards and provide a scalable model that can subsequently be extended to other disease areas and connected with international genomic data-sharing initiatives.

Ongoing Work

Our participating institutions have generated genomic data from more than 1,000 patients with hematological disorders through targeted gene panels and whole-exome sequencing. Some cases are resolved through the identification of established pathogenic or likely pathogenic variants. However, a substantial proportion remains unresolved, with variants classified as variants of uncertain significance (VUS).

Many of these variants are rare or potentially novel and are not represented in international genomic databases. In the absence of a mechanism for sharing and comparing genomic data within the local population, we currently cannot determine whether the same variant has been observed in other Pakistani patients, whether it occurs repeatedly within particular disease phenotypes, or whether it may represent a population-specific disease-associated variant.

References

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This limitation makes it difficult to prioritise VUS for further investigation, including functional studies, and may delay diagnosis for patients and families. A national data-sharing framework would allow participating institutions to identify recurrent variants, correlate variants with clinical phenotypes, and collectively build evidence for variant interpretation.

Our existing dataset and ongoing diagnostic activities therefore provide a strong foundation for the proposed pilot. The project will build upon these resources to develop a structured and interoperable approach for responsible genomic data discovery and sharing.