Long-read sequencing links intronic TG repeats to CD36 deficiency patterns

The study, published in BMC Immunology, analyzed blood samples from donors with type I and type II CD36 deficiency as well as healthy controls, and its findings point to a regulatory role for noncoding DNA in this disorder.

CD36 is known to play a distinct role in immune regulation, lipid transport, and hemostasis. Although CD36 antigen deficiency has been documented in certain populations, the underlying genetic mechanisms have remained unclear.

In the study, the team collected 100 blood samples from donors with type I and type II CD36 deficiency and from healthy controls, then employed long-read sequencing to analyze the haplotype of the CD36 gene. The long reads allowed the researchers to resolve how variants along the gene are arranged together, something short-read approaches often cannot do reliably.

The results showed that all haplotypes harbored (TG)n repeats in intron 3, with repeat numbers ranging from 11 to 20. These repeats were tightly linked to three distinct downstream single nucleotide variant patterns, which the authors labeled Patterns A, B, and C, occurring after the c.748+757 A>G site. In other words, the length of the repeat tract reliably predicted which downstream variant pattern accompanied it on the same haplotype.

The distribution of these haplotype combinations differed strikingly between the two deficiency types. The haplotype combination (TG)n-B was predominant in type I CD36 deficiency, whereas (TG)n-C was significantly dominant in type II cases. This association is particularly notable because type II deficiency lacks known mutations in the coding region of the gene, leaving the cause of that phenotype previously unexplained.

The authors conclude that these findings suggest a regulatory role for the intronic (TG)n repeats and their associated haplotypes in manifesting CD36 deficiency, particularly for type II deficiency. The study presents new insights into the noncoding genetic architecture of CD36, an area that standard variant-focused analyses have largely overlooked.

Beyond the specific gene, the work highlights the application of long-read sequencing in resolving complex haplotypes.

As an early-access, peer-reviewed accepted article, the study is citable and carries a permanent DOI, though the version is subject to further edits before the final Version of Record.

Subject of Research: Genetic haplotype patterns of intronic (TG)n repeats in the CD36 gene associated with CD36 deficiency phenotypes

Article Title: Long-read sequencing identifies single nucleotide variant patterns of (TG)n repeats linked to CD36 deficiency phenotypes

Article References: Liu, T., Wu, F., Sun, L., Fu, W., He, R., Yao, Y., & Liang, S. (2026). Long-read sequencing identifies single nucleotide variant patterns of (TG)n repeats linked to CD36 deficiency phenotypes. BMC Immunology. https://doi.org/10.1186/s12865-026-00915-8

Image Credits: AI Generated

DOI: 10.1186/s12865-026-00915-8

Keywords: CD36 deficiency, long-read sequencing, haplotype, (TG)n repeats, intron 3, single nucleotide variants, BMC Immunology, platelets, noncoding DNA, type I deficiency, type II deficiency, genetics