Journal of Human Genetics最新文献

Two-hit mutation causes Wilms tumor in an individual with FBXW7-related neurodevelopmental syndrome. FBXW7相关神经发育综合征患者的Wilms瘤是由两个基因突变引起的。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-10-16 DOI: 10.1038/s10038-024-01299-6

Yoko Saito, Dai Keino, Yukiko Kuroda, Yumi Enomoto, Takuya Naruto, Yukichi Tanaka, Mio Tanaka, Hidehito Usui, Norihiko Kitagawa, Masakatsu Yanagimachi, Kenji Kurosawa

引用次数: 0

Biallelic missense CEP55 variants cause prenatal MARCH syndrome. 双倍错义 CEP55 变异导致产前 MARCH 综合征。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-10-16 DOI: 10.1038/s10038-024-01298-7

Li Fu, Yuka Yamamoto, Rie Seyama, Nana Matsuzawa, Mariko Nagaoka, Takashi Yao, Keisuke Hamada, Kazuhiro Ogata, Toshifumi Suzuki, Naomi Tsuchida, Yuri Uchiyama, Eriko Koshimizu, Kazuharu Misawa, Satoko Miyatake, Takeshi Mizuguchi, Atsushi Fujita, Atsuo Itakura, Naomichi Matsumoto

{"title":"Biallelic missense CEP55 variants cause prenatal MARCH syndrome.","authors":"Li Fu, Yuka Yamamoto, Rie Seyama, Nana Matsuzawa, Mariko Nagaoka, Takashi Yao, Keisuke Hamada, Kazuhiro Ogata, Toshifumi Suzuki, Naomi Tsuchida, Yuri Uchiyama, Eriko Koshimizu, Kazuharu Misawa, Satoko Miyatake, Takeshi Mizuguchi, Atsushi Fujita, Atsuo Itakura, Naomichi Matsumoto","doi":"10.1038/s10038-024-01298-7","DOIUrl":"https://doi.org/10.1038/s10038-024-01298-7","url":null,"abstract":"CEP55 encodes centrosomal protein 55 kDa, which plays a crucial role in mitosis, particularly cytokinesis. Biallelic CEP55 variants cause MARCH syndrome (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly). Here, we describe a Japanese family with two affected siblings harboring novel compound heterozygous CEP55 variants, NM_001127182: c.[1357 C > T];[1358 G > A] p.[(Arg453Cys)];[(Arg453His)]. Both presented clinically with typical lethal MARCH syndrome. Although a combination of missense and nonsense variants has been reported previously, this is the first report of biallelic missense CEP55 variants. These variants biallelically affected the same amino acid, Arg453, in the last 40 amino acids of CEP55. These residues are functionally important for CEP55 localization to the midbody during cell division, and may be associated with severe clinical outcomes. More cases of pathogenic CEP55 variants are needed to establish the genotype-phenotype correlation.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic analysis of a Yayoi individual from the Doigahama site provides insights into the origins of immigrants to the Japanese Archipelago. 通过对土居浜遗址中的弥生个体进行基因分析，可以了解日本列岛移民的起源。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-10-15 DOI: 10.1038/s10038-024-01295-w

Jonghyun Kim, Fuzuki Mizuno, Takayuki Matsushita, Masami Matsushita, Saki Aoto, Koji Ishiya, Mami Kamio, Izumi Naka, Michiko Hayashi, Kunihiko Kurosaki, Shintaroh Ueda, Jun Ohashi

{"title":"Genetic analysis of a Yayoi individual from the Doigahama site provides insights into the origins of immigrants to the Japanese Archipelago.","authors":"Jonghyun Kim, Fuzuki Mizuno, Takayuki Matsushita, Masami Matsushita, Saki Aoto, Koji Ishiya, Mami Kamio, Izumi Naka, Michiko Hayashi, Kunihiko Kurosaki, Shintaroh Ueda, Jun Ohashi","doi":"10.1038/s10038-024-01295-w","DOIUrl":"https://doi.org/10.1038/s10038-024-01295-w","url":null,"abstract":"Mainland Japanese have been recognized as having dual ancestry, originating from indigenous Jomon people and immigrants from continental East Eurasia. Although migration from the continent to the Japanese Archipelago continued from the Yayoi to the Kofun period, our understanding of these immigrants, particularly their origins, remains insufficient due to the lack of high-quality genome samples from the Yayoi period, complicating predictions about the admixture process. To address this, we sequenced the whole nuclear genome of a Yayoi individual from the Doigahama site in Yamaguchi prefecture, Japan. A comprehensive population genetic analysis of the Doigahama Yayoi individual, along with ancient and modern populations in East Asia and Northeastern Eurasia, revealed that the Doigahama Yayoi individual, similar to Kofun individuals and modern Mainland Japanese, had three distinct genetic ancestries: Jomon-related, East Asian-related, and Northeastern Siberian-related. Among non-Japanese populations, the Korean population, possessing both East Asian-related and Northeastern Siberian-related ancestries, exhibited the highest degree of genetic similarity to the Doigahama Yayoi individual. The analysis of admixture modeling for Yayoi individuals, Kofun individuals, and modern Japanese respectively supported a two-way admixture model assuming Jomon-related and Korean-related ancestries. These results suggest that between the Yayoi and Kofun periods, the majority of immigrants to the Japanese Archipelago originated primarily from the Korean Peninsula.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population. 开发日本人口中与血清素-转运体相关的多态性区域（5-HTTLPR）的多等位基因估算方法。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-25 DOI: 10.1038/s10038-024-01296-9

Yutaro Yanagida, Izumi Naka, Yutaka Nakachi, Tempei Ikegame, Kiyoto Kasai, Naoto Kajitani, Minoru Takebayashi, Miki Bundo, Jun Ohashi, Kazuya Iwamoto

{"title":"Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population.","authors":"Yutaro Yanagida, Izumi Naka, Yutaka Nakachi, Tempei Ikegame, Kiyoto Kasai, Naoto Kajitani, Minoru Takebayashi, Miki Bundo, Jun Ohashi, Kazuya Iwamoto","doi":"10.1038/s10038-024-01296-9","DOIUrl":"https://doi.org/10.1038/s10038-024-01296-9","url":null,"abstract":"Serotonin-transporter-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the promoter region of serotonin transporter gene, is classified into short (S) and long (L) alleles. Initial case-control association studies claiming the risks of the S allele in depression and anxiety were not completely supported by recent studies. However, most studies, especially those on East Asian populations, have overlooked the complexity of 5-HTTLPR, which involves multiple different alleles with distinct functional properties. To address this issue, distinguishing multiple 5-HTTLPR alleles is essential. Here, using the 5-HTTLPR genotypes previously determined by exhaustive Sanger sequencing of approximately 1,500 Japanese subjects and their comprehensive SNP data, we constructed a method for 5-HTTLPR genotype imputation. We identified 28 tag SNPs for the imputation of four major 5-HTTLPR alleles, which collectively account for 97.6% of 5-HTTLPR alleles in the Japanese population. Our imputation method, achieved an accuracy of 0.872 in cross-validation, will contribute to association analysis of 5-HTTLPR in the Japanese subjects.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome. 更正：基于综合序列分析的GBA1变异与MSA的关联研究--取决于人类参考基因组的短读序列分析的陷阱。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-20 DOI: 10.1038/s10038-024-01293-y

Kenta Orimo, Jun Mitsui, Takashi Matsukawa, Masaki Tanaka, Junko Nomoto, Hiroyuki Ishiura, Yosuke Omae, Yosuke Kawai, Katsushi Tokunaga, Tatsushi Toda, Shoji Tsuji

引用次数: 0

Biallelic TXNDC15 variants associated with Joubert syndrome-related molar tooth sign and forebrain malformation. 与朱伯特综合征相关的臼齿征和前脑畸形有关的双叶TXNDC15变体。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-09-20 DOI: 10.1038/s10038-024-01290-1

Yukiko Kuroda, Tamaki Ikegawa, Ayumi Kato, Noriko Aida, Takuya Naruto, Kenji Kurosawa

{"title":"Biallelic TXNDC15 variants associated with Joubert syndrome-related molar tooth sign and forebrain malformation.","authors":"Yukiko Kuroda, Tamaki Ikegawa, Ayumi Kato, Noriko Aida, Takuya Naruto, Kenji Kurosawa","doi":"10.1038/s10038-024-01290-1","DOIUrl":"https://doi.org/10.1038/s10038-024-01290-1","url":null,"abstract":"TXNDC15 encodes thioredoxin domain-containing protein 15, a protein disulfide isomerase that plays a role in ciliogenesis. Biallelic TXNDC15 variants have been reported in six individuals of Meckel syndrome (MKS) with perinatal lethal phenotypes, but have not been reported in patients with Joubert syndrome (JS). Here, we describe a 1-year-old female patient with compound heterozygous TXNDC15 variants demonstrating cerebellar vermis hypoplasia with the molar tooth sign, mild holoprosencephaly, and cortical abnormalities. She had severe developmental delay and epilepsy. Her clinical features were similar to those of JS, but distinctive forebrain abnormalities were also noted including mild holoprosencephaly and cortical abnormalities, which have been reported in a severe form of ciliopathy. Biallelic TXNDC15 variants manifest as overlapping phenotypes of JS and MKS, including the molar tooth sign, cortical dysgenesis, and mild holoprosencephaly. This report supports the hypothesis that JS and MKS are spectrum ciliopathy disorders with overlapping causative genes and hypomorphic TXNDC15 variants might contribute to JS.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy 全国癌症基因组剖析二次发现调查：包括液体活检在内的调查

IF 3.5 3区生物学

Journal of Human Genetics Pub Date : 2024-09-17 DOI: 10.1038/s10038-024-01294-x

Saki Shimada, Takahiro Yamada, Akari Minamoto, Manami Matsukawa, Ichiro Yabe, Hiroshi Tada, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi

{"title":"Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy","authors":"Saki Shimada, Takahiro Yamada, Akari Minamoto, Manami Matsukawa, Ichiro Yabe, Hiroshi Tada, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi","doi":"10.1038/s10038-024-01294-x","DOIUrl":"https://doi.org/10.1038/s10038-024-01294-x","url":null,"abstract":"We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating common mutations in ATP7B gene and the prevalence of Wilson's disease in the Thai population using population-based genome-wide datasets. 利用基于人群的全基因组数据集调查泰国人群中 ATP7B 基因的常见突变和威尔逊氏病的患病率。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-28 DOI: 10.1038/s10038-024-01292-z

Paravee Own-Eium, Donniphat Dejsuphong, Prin Vathesatogkit, Piyamitr Sritara, Thanyachai Sura, Wichai Aekplakorn, Bhoom Suktitipat, Jakris Eu-Ahsunthornwattana

{"title":"Investigating common mutations in ATP7B gene and the prevalence of Wilson's disease in the Thai population using population-based genome-wide datasets.","authors":"Paravee Own-Eium, Donniphat Dejsuphong, Prin Vathesatogkit, Piyamitr Sritara, Thanyachai Sura, Wichai Aekplakorn, Bhoom Suktitipat, Jakris Eu-Ahsunthornwattana","doi":"10.1038/s10038-024-01292-z","DOIUrl":"https://doi.org/10.1038/s10038-024-01292-z","url":null,"abstract":"Wilson's disease (WD) is a rare metabolic disorder caused by variations in the ATP7B gene. It usually manifests hepatic, neurologic, and psychiatric symptoms due to excessive copper accumulation. The prevalence of WD and its common variants differ across populations. This study aimed to examine these aspects of WD within the Thai population, where information has been limited. We reviewed ClinVar and the Wilson Disease Mutation Database, organizing variants classified as pathogenic or likely pathogenic in one or both databases as \"relaxed\" and \"strict\" lists. Allele frequencies were estimated from genotyping array data (Asian Screening Array: ASA; Illumina Corp, CA) of 6291 Thai subjects, which also underwent genotype imputation. The prevalence of WD in the Thai population was estimated assuming Hardy-Weinberg Equilibrium. The strict list yielded a prevalence of 1/24,128 (carrier frequency=1/78), while the relaxed list yielded a prevalence of 1/9971 (carrier frequency=1/50). The most common WD variants in Thai subjects were c.2333 G > T, c.3443 T > C, and c.813 C > A from the strict list, and c.3316 G > A and c.2605 G > A from the relaxed list. The ASA chip covered approximately 59 and 24% of WD variants from the strict and relaxed lists, respectively. Based on the estimated prevalence, a carrier screening program for WD is not currently required in Thailand. However, as genotyping services become more affordable and accessible, such a program would facilitate early identification, treatment, and prevention of WD.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Artificial intelligence in medical genomics 医学基因组学中的人工智能。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-27 DOI: 10.1038/s10038-024-01282-1

Yoichiro Kamatani, Tadashi Kaname

引用次数: 0

Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study. 健康生活方式与多基因高风险人群肥胖患病率下降相关：TMM社区队列研究。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-08-22 DOI: 10.1038/s10038-024-01280-3

Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Makoto Sasaki, Atsushi Shimizu

{"title":"Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study.","authors":"Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Makoto Sasaki, Atsushi Shimizu","doi":"10.1038/s10038-024-01280-3","DOIUrl":"https://doi.org/10.1038/s10038-024-01280-3","url":null,"abstract":"Obesity and overweight, fundamental components of the metabolic syndrome, predispose individuals to lifestyle-related diseases. The extent to which adopting healthy lifestyles can reduce obesity risk, even in those with a high genetic risk, remains uncertain. Our aim was to assess the extent to which lifestyle modifications can improve outcomes in individuals with a high polygenic score (PGS) for obesity. We quantified the genetic risk of obesity using PGSs. Four datasets from the Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) were employed in the study. One dataset (n = 9958) was used to select the best model for calculating PGS. The remaining datasets (total n = 69,341) were used in a meta-analysis to validate the model and to evaluate associated risks. The odds ratio (OR) for obesity risk in the intermediate (11th-90th percentiles in the dataset) and high PGS categories (91st-100th) was 2.27 [95% confidence intervals: 2.12-2.44] and 4.83 [4.45-5.25], respectively, compared to that in the low PGS category (1st-10th). Trend analysis showed that an increase in leisure-time physical activity was significantly associated with reduced obesity risk across all genetic risk categories, representing an OR of 0.9 [0.87-0.94] even among individuals in the high PGS category. Similarly, sodium intake displayed a positive association with obesity across all genetic risk categories, yielding an OR of 1.24 [1.17-1.31] in the high PGS category. The risk of obesity was linked to the adoption of healthy lifestyles, even in individuals with high PGS. Our results may provide perspectives for integrating PGSs into preventive medicine.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0