CARD9 gene are more susceptible to severe fungal infections. However, tracking the origin of these mutations is complicated due to the fact that specific variants of the CARD9 gene are found in different populations around the world. A recent study conducted genetic analyses on Japanese, Korean, and Chinese patients, and found that they all shared a CARD9 gene variant that can be traced back to a common ancestor from less than 4,000 years ago. Fungal infections can be extremely dangerous, particularly when they affect vital organs or the central nervous system.D9 gene is more vulnerable to invasive fungal infections because the protein it produces is essential for regulating the immune system. Scientists at Tokyo Medical and Dental University (TMDU) have found that a specific variant of CARD9, which is common in northern China, Korea, and Japan, may have originated from a common ancestor.
In a study published on May 17, 2024, in the Journal of Clinical Immunology, TMDU researchers conducted genetic analyses on Japanese and Korean patients who experienced severe or recurring fungal infections.The aim was to bring attention to the genetic and clinical characteristics of people affected by CARD9 deficiency in East Asia.
The research involved five patients with CARD9 deficiency. Two of these patients, who were from Japan, were newly found to have biallelic variants of CARD9 after DNA sequencing by the researchers due to their history of fungal infections. In addition to these two patients, three others – two from Korea and one from Japan – were also found to carry a CARD9 variant known as c.820dup.ARD9 deficiency is more prevalent in certain regions such as North Africa, the Middle East, and China. The distribution of CARD9 variants is also uneven, with the c.820dup variant being particularly common in China,” explained Prof. Hirokazu Kanegane. In a study, all five patients shared the same variant, leading the researchers to consider the “founder effect” as a possible explanation. This effect occurs when a variant becomes widespread in a population that originated from a small group of ancestors. To test their theory, the researchers conducted haplotype analyses. In simple terms, they scrutinized the genetic markers surrounding the variant to confirm their hypothesis.The researchers focused on groups of genes inherited from a parent (haplotypes) to compare them among five patients and with previously sequenced haplotypes from Chinese CARD9-deficient patients. They discovered that all haplotypes containing the c.820dup variant were identical, providing strong evidence. After conducting statistical genetic analyses, the researchers estimated the age of the c.820dup variant to be between 2,000 and 4,000 years. The estimated variant’s age and distribution in Japan, Korea, and China align perfectly with the historical timeline.The history of the East Asia region suggests that modern Japanese and Koreans have a genetic background that can be traced back to northern China. It is believed that during the late Neolithic to the Bronze Age, people migrated from northern China to Korea and Japan, bringing with them rice and language. Professor Kanegane notes that the origins of the variant identified in this study align with this historical period. The conclusion is that this variant stems from a common ancestor estimated to have lived less than 4,000 years ago. Furthermore, although the observed variant was the same, the clinical presentation of patients from Japan and Korea differed.The medical records show that Chinese patients had a higher prevalence of black mold infections caused by the genus Phialophora compared to patients from Japan and Korea. The researchers attribute this difference to environmental factors, possibly related to the more rural lifestyle in northern China. This interdisciplinary study contributes to our understanding of anthropology, genetics, and medicine, and provides insight into how genetic variants can spread across different regions and generations.
