Genetic Mutations Identified in Human Blood Diseases

A dozen mutations have been identified in the human genome that are involved in significant changes in complete blood counts and that explain the onset of occasionally severe biological disorders.

The number of red and white blood cells and platelets in the blood is an important clinical marker, as it helps doctors detect many hematological and other diseases and can also be used to determine the effectiveness of therapy for certain pathologies.


Scientists at the Montreal Heart Institute (MHI; Montreal, QC, Canada) and their international collaborators analyzed the DNA of 6,796 people who had donated specimens to the MHI Biobank by looking specifically at segments of DNA directly involved in protein function in the body. They also analyzed hemoglobin concentration, hematocrit levels, white blood cell (WBC) counts and platelet counts in 31,340 individuals genotyped on an exome array.

Blood cell counts and other related phenotypes were automatically generated with the UniCel DxH 800 cellular analysis system (Beckman Coulter; Brea, CA, USA). DNA samples from the clinical coordinating center were sent for genotyping and were placed on 96-well plates for processing using the HumanExome v1.0 Single Nucleotide Polymorphism (SNP) array (Illumina; San Diego, CA, USA).

The scientists specifically identified a significant mutation in the gene that encodes erythropoietin (EPO), a hormone that controls the production of red blood cells. They also identified a mutation in the Janus kinase 2 (JAK2) gene, which is responsible for a 50% increase in platelet counts and, in certain cases, for the onset of bone marrow diseases that can lead to leukemia.

The authors concluded that their results clearly demonstrated that rare and low-frequency coding variants contribute to phenotypic variation in human populations. The new missense variants in key regulators of hematopoiesis that were discovered have potential implications for diagnostic screening and drug development in a variety of hematological and inflammatory disorders. The study was published on April 28, 2014, in the journal Nature Genetics.

Related Links:
Montreal Heart Institute
Beckman Coulter 
Illumina