A recently published study found a link between key haplotypes, or DNA markers, and type I CD36 deficiency, which could contribute to the development of fetal and neonatal alloimmune thrombocytopenia (FNAIT) and/or platelet transfusion refractoriness (PTR).
The study, published in Scientific Reports, utilized single-molecule long-read sequencing to conduct a thorough haplotype analysis linked to type I CD36 deficiency and FNAIT.
CD36 is expressed on various types of cells, including monocytes, erythrocytes, mammary epithelial cells, microvascular endothelial cells, and megakaryocytes. The expression of CD36 on red blood cells, however, is lower.
To date, two subgroups of CD36 deficiency have been reported: type I, in which there is a total lack of expression, and type II, which is absent on platelets but found on monocytes. Although persons with type I deficiency are usually healthy, they may develop anti-CD36 antibodies during a pregnancy or following a blood transfusion.
Read more about FNAIT prognosis
The CD36 gene spans around 50,000 base pairs. Research in general has been focused on identification of CD36 mutations via next-generation sequencing (NGS) and Sanger sequencing, with very limited assessment of haplotypes reported.
Study methods and findings
Realizing that research has aimed to identify mutations via Sanger sequencing and NGS, but that associations among CD36 gene variants—haplotypes, in particular—remain to be elucidated, the researchers sought to obtain blood samples from donors with type I and type II CD36 deficiencies, as well as from healthy controls. They used single-molecule long-read sequencing, which is also known as third-generation sequencing, of genomic DNA to explore the genetic basis of CD36.
A total of 180 variants were identified within the CD36 gene among 37 donors and patients. In 12 of these variants, the amino acid sequence was shown to be altered.
Among these 12 variants, four were classified as premature termination mutations that lead to protein truncation. A truncated protein is one that is shorter in length than the full-length version of that particular protein. Seven of the other variants were considered to be nonsynonymous.
Fisher’s exact test was utilized to evaluate the relationships between genetic variants and the observed phenotypes. There were consistent patterns of haplotype blocks observed in those groups with significant associations. Of note, a stronger association was observed between the variants in the 5’ block and type I deficiency.
In comparison, the significance of associations with type II classifications were diverse, which was indicative of the fact that these variants are associated more specifically with type I deficiency than with type I and type II deficiencies
The “technology [analyzed] facilitated a detailed haplotype analysis associated with type I CD36 deficiency and FNAIT,” the authors explained. “Moreover, molecular genetic analysis indicated that mutations in the 5’-UTR might play a significant role in the pathogenesis of CD36 deficiency,” they concluded.
