著者

Eri Kikkawa Masafumi Tanaka Tomi T. Tsuda Koichi Murata Taeko K. Naruse Akinori Kimura

出版者

Japanese Society for Histocompatibility and Immunogenetics

雑誌

日本組織適合性学会誌 (ISSN:21869995)

巻号頁・発行日

vol.26, no.3, pp.195-203, 2019 (Released:2019-12-27)

参考文献数

34

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Endangered penguins are in need of the genetic management to estimate the risk for loss of genetic diversity from populations resulting from habitat fragmentation or inbreeding. However, as for genome diversity in penguin species, there are limited reports and it is insufficient to give useful and appropriate information. In the present study, we obtained the full length sequence of the MHC class II gene, which is expected to be a useful genetic marker for biodiversity in conservation genetics. The 4.4 kb genome region containing two novel genes was determined for nucleotide sequences using genomic DNA extracted from Humboldt penguin, by using the inverse PCR method. Homology analysis of MHC class II genes with those from other birds suggested that the novel two genes were alpha and beta genes. In addition, phylogenetic analysis suggested that the beta gene of penguins was clustered with the beta genes from waterfowl. These observations provide basic information on the structure of MHC class II locus to relieve the genetic diversity of penguin species.

著者

Kayoko Hirayama-Yamada Natsuko Inagaki Takeharu Hayashi Akinori Kimura

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.62, no.2, pp.359-366, 2021-03-30 (Released:2021-03-30)

参考文献数

30

被引用文献数

6

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Dilated cardiomyopathy (DCM) is a common cause of heart failure. TTN, which encodes titin protein, is a representative causative gene of DCM, and is presented mainly as a truncation variant. However, TTN truncation variants are also found in healthy individuals, and it is therefore important to evaluate the pathogenicity of each variant. In this study, we analyzed 67 cardiomyopathy-associated genes in a male Japanese patient who was hospitalized for recurrent severe heart failure and identified a novel truncation variant, TTN Ser17456Arg fs*14. This TTN truncation variant was located in the A-band region. Moreover, the patient's mother with heart failure harbored the same variant, whereas the father and brother without heart failure did not harbor the variant. To examine the functional changes associated with the truncation variant, H9c2 cells were subjected to genome editing to generate cells with a homologous truncation variant. The cells were differentiated using all-trans-retinoic acid, and the mRNA expression of skeletal actin and cardiac actin were found to be increased and decreased, respectively, consistent with known changes in patients with DCM or heart failure. In contrast, another cell with the titin truncation variant used as a control showed no changes in heart failure-related genes. In summary, we found a novel TTN truncation variant in familial DCM patients and confirmed its functional changes using a relatively simple cell model. The novel truncation variant was identified as a pathogenic and disease-causing mutation.