Journal of Human Genetics最新文献_第7页

FBXO11 variants are associated with intellectual disability and variable clinical manifestation in Chinese affected individuals FBXO11变体与中国患者的智力残疾和不同临床表现有关。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-05-13 DOI: 10.1038/s10038-024-01255-4

Xin Pan, Li Liu, Xu Zhang, Xianglan Tang, Guanhua Qian, Hao Qiu, Shuhong Lin, Hong Yao, Xiaojing Dong, Bo Tan

{"title":"FBXO11 variants are associated with intellectual disability and variable clinical manifestation in Chinese affected individuals","authors":"Xin Pan, Li Liu, Xu Zhang, Xianglan Tang, Guanhua Qian, Hao Qiu, Shuhong Lin, Hong Yao, Xiaojing Dong, Bo Tan","doi":"10.1038/s10038-024-01255-4","DOIUrl":"10.1038/s10038-024-01255-4","url":null,"abstract":"F-box protein 11 (FBXO11) is a member of F-Box protein family, which has recently been proved to be associated with intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA, OMIM: 618089). In this study, 12 intellectual disability individuals from 5 Chinese ID families were collected, and whole exome sequencing (WES), sanger sequencing, and RNA sequencing (RNA-seq) were conducted. Almost all the affected individuals presented with mild to severe intellectual disability (12/12), global developmental delay (10/12), speech and language development delay (8/12) associated with a range of alternate features including increased body weight (7/12), short stature (6/12), seizures (3/12), reduced visual acuity (4/12), hypotonia (1/12), and auditory hallucinations and hallucinations (1/12). Distinguishingly, malformation was not observed in all the affected individuals. WES analysis showed 5 novel FBXO11 variants, which include an inframe deletion variant, a missense variant, two frameshift variants, and a partial deletion of FBXO11 (exon 22–23). RNA-seq indicated that exon 22–23 deletion of FBXO11 results in a new mRNA structure. Conservation and protein structure prediction demonstrated deleterious effect of these variants. The DEGs analysis revealed 148 differentially expressed genes shared among 6 affected individuals, which were mainly associated with genes of muscle and immune system. Our research is the first report of FBXO11-associated IDDFBA in Chinese individuals, which expands the genetic and clinical spectrum of this newly identified NDD/ID syndrome.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 8","pages":"391-400"},"PeriodicalIF":2.6,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916565","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

A novel pathogenic mitochondrial DNA variant m.4344T>C in tRNAGln causes developmental delay tRNAGln 中的一种新型致病线粒体 DNA 变异 m.4344T>C 会导致发育迟缓。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-05-10 DOI: 10.1038/s10038-024-01254-5

Xiaojie Yin, Qiyu Dong, Shuanglong Fan, Lina Yang, Hao Li, Yijun Jin, Mahlatsi Refiloe Laurentinah, Xiandan Chen, Aliaksei Sysa, Hezhi Fang, Jianxin Lyu, Yongguo Yu, Ya Wang

{"title":"A novel pathogenic mitochondrial DNA variant m.4344T>C in tRNAGln causes developmental delay","authors":"Xiaojie Yin, Qiyu Dong, Shuanglong Fan, Lina Yang, Hao Li, Yijun Jin, Mahlatsi Refiloe Laurentinah, Xiandan Chen, Aliaksei Sysa, Hezhi Fang, Jianxin Lyu, Yongguo Yu, Ya Wang","doi":"10.1038/s10038-024-01254-5","DOIUrl":"10.1038/s10038-024-01254-5","url":null,"abstract":"Mitochondrial diseases are a group of genetic diseases caused by mutations in mitochondrial DNA and nuclear DNA. However, the genetic spectrum of this disease is not yet complete. In this study, we identified a novel variant m.4344T>C in mitochondrial tRNAGln from a patient with developmental delay. The mutant loads of m.4344T>C were 95% and 89% in the patient’s blood and oral epithelial cells, respectively. Multialignment analysis showed high evolutionary conservation of this nucleotide. TrRosettaRNA predicted that m.4344T>C variant would introduce an additional hydrogen bond and alter the conformation of the T-loop. The transmitochondrial cybrid-based study demonstrated that m.4344T>C variant impaired the steady-state level of mitochondrial tRNAGln and decreased the contents of mitochondrial OXPHOS complexes I, III, and IV, resulting in defective mitochondrial respiration, elevated mitochondrial ROS production, reduced mitochondrial membrane potential and decreased mitochondrial ATP levels. Altogether, this is the first report in patient carrying the m.4344T>C variant. Our data uncover the pathogenesis of the m.4344T>C variant and expand the genetic mutation spectrum of mitochondrial diseases, thus contributing to the clinical diagnosis of mitochondrial tRNAGln gene variants-associated mitochondrial diseases.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 8","pages":"381-389"},"PeriodicalIF":2.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904512","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

Fundamentals for predicting transcriptional regulations from DNA sequence patterns 从 DNA 序列模式预测转录调控的基本原理。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-05-10 DOI: 10.1038/s10038-024-01256-3

Masaru Koido, Kohei Tomizuka, Chikashi Terao

{"title":"Fundamentals for predicting transcriptional regulations from DNA sequence patterns","authors":"Masaru Koido, Kohei Tomizuka, Chikashi Terao","doi":"10.1038/s10038-024-01256-3","DOIUrl":"10.1038/s10038-024-01256-3","url":null,"abstract":"Cell-type-specific regulatory elements, cataloged through extensive experiments and bioinformatics in large-scale consortiums, have enabled enrichment analyses of genetic associations that primarily utilize positional information of the regulatory elements. These analyses have identified cell types and pathways genetically associated with human complex traits. However, our understanding of detailed allelic effects on these elements’ activities and on-off states remains incomplete, hampering the interpretation of human genetic study results. This review introduces machine learning methods to learn sequence-dependent transcriptional regulation mechanisms from DNA sequences for predicting such allelic effects (not associations). We provide a concise history of machine-learning-based approaches, the requirements, and the key computational processes, focusing on primers in machine learning. Convolution and self-attention, pivotal in modern deep-learning models, are explained through geometrical interpretations using dot products. This facilitates understanding of the concept and why these have been used for machine learning for DNA sequences. These will inspire further research in this genetics and genomics field.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 10","pages":"499-504"},"PeriodicalIF":2.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s10038-024-01256-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts 在两个拉丁美洲队列中探索外来混血与注意力缺陷多动障碍遗传易感性之间的关系。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-05-07 DOI: 10.1038/s10038-024-01246-5

Nicolás Garzón Rodríguez, Ignacio Briceño-Balcázar, Humberto Nicolini, José Jaime Martínez-Magaña, Alma D. Genis-Mendoza, Julio C. Flores-Lázaro, Jorge A. Villatoro Velázquez, Marycarmen Bustos Gamiño, Maria Elena Medina-Mora, Maria Fernanda Quiroz-Padilla

{"title":"Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts","authors":"Nicolás Garzón Rodríguez, Ignacio Briceño-Balcázar, Humberto Nicolini, José Jaime Martínez-Magaña, Alma D. Genis-Mendoza, Julio C. Flores-Lázaro, Jorge A. Villatoro Velázquez, Marycarmen Bustos Gamiño, Maria Elena Medina-Mora, Maria Fernanda Quiroz-Padilla","doi":"10.1038/s10038-024-01246-5","DOIUrl":"10.1038/s10038-024-01246-5","url":null,"abstract":"Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e−5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e−8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation’s impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 8","pages":"373-380"},"PeriodicalIF":2.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study 印度-亚洲不孕妇女中 FSH-R Asn680Ser 和 Ala307Thr 受体多态性的发生率及其与抗逆转录病毒疗法结果的相关性--一项前瞻性队列研究。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-04-25 DOI: 10.1038/s10038-024-01251-8

Reeta Mahey, Monika Rajput, Rima Dada, Mani Kalaivani, Monica Gupta, Rohitha Cheluvaraju, Neena Malhotra, Monika Saini, Ashok Bhatt, Manoj Kumar, Neeta Singh, Neerja Bhatla

{"title":"Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study","authors":"Reeta Mahey, Monika Rajput, Rima Dada, Mani Kalaivani, Monica Gupta, Rohitha Cheluvaraju, Neena Malhotra, Monika Saini, Ashok Bhatt, Manoj Kumar, Neeta Singh, Neerja Bhatla","doi":"10.1038/s10038-024-01251-8","DOIUrl":"10.1038/s10038-024-01251-8","url":null,"abstract":"The present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in ovarian response parameters, oocyte yield, and CLBR among the three genotype groups. Empty follicle syndrome (EFS) was highest in women with AA or AG type at both positions. On categorisation of unexpected poor responders according to POSEIDON stratification; GG genotype at both positions had the lowest risk ratio of low-oocyte yield in ART cycles, but these differences were not statistically significant. This is the largest study from Indian ethnicity showing GG (Ser/Ser) genotype is most common among fertile women. The effect of FSH-R genotypes is very marginal on IVF parameters and is not reflected in CLBR. More prospective data may be required on the correlation of these genotypes with genuine EFS, thus stratifying the next cycles with self or donor oocytes. Routine genetic testing of FSH-R polymorphism should not be done except in a research setting. As both 680 and 307 positions are in linkage disequilibrium, only 680 position analysis may be done in a research setting.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 8","pages":"365-372"},"PeriodicalIF":2.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653303","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

Mediation role of DNA methylation in association between handgrip strength and cognitive function in monozygotic twins DNA甲基化在单卵双胎手握力和认知功能之间的关联中的中介作用

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-04-23 DOI: 10.1038/s10038-024-01247-4

Jin Liu, Weijing Wang, Jia Luo, Haiping Duan, Chunsheng Xu, Xiaocao Tian, Shumin Chen, Lin Ge, Dongfeng Zhang

{"title":"Mediation role of DNA methylation in association between handgrip strength and cognitive function in monozygotic twins","authors":"Jin Liu, Weijing Wang, Jia Luo, Haiping Duan, Chunsheng Xu, Xiaocao Tian, Shumin Chen, Lin Ge, Dongfeng Zhang","doi":"10.1038/s10038-024-01247-4","DOIUrl":"10.1038/s10038-024-01247-4","url":null,"abstract":"Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediation analysis. In order to do an ontology enrichment study for CpGs, the GREAT program was used. There was a significant positive association between handgrip strength and cognitive function (β = 0.194, P < 0.001). The association between handgrip strength and DNAm of 124 CpGs was found to be statistically significant at a significance level of P < 1 × 10−4. Fifteen differentially methylated regions (DMRs) related to handgrip strength were found in genes such as SNTG2, KLB, CDH11, and PANX2. Of the 124 CpGs, 4 within KRBA1, and TRAK1 mediated the association between handgrip strength and cognitive function: each 1 kg increase in handgrip strength was associated with a potential decrease of 0.050 points in cognitive function scores, mediated by modifications in DNAm. The parallel mediating effect of these 4 CpGs was −0.081. The presence of DNAm variation associated with handgrip strength may play a mediated role in the association between handgrip strength and cognitive function.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 8","pages":"357-363"},"PeriodicalIF":2.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140665731","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

Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases 探索远端Xq28重复综合征的遗传和临床渗透性：从47个未发表的新病例中获得的启示

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-04-18 DOI: 10.1038/s10038-024-01252-7

Michal Levy, Eyal Elron, Mordechai Shohat, Shira Lifshitz, Sarit Kahana, Hagit Shani, Anat Grossman, Shirly Amar, Ginat Narkis, Lena Sagi-Dain, Lina Basel-Salmon, Idit Maya

{"title":"Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases","authors":"Michal Levy, Eyal Elron, Mordechai Shohat, Shira Lifshitz, Sarit Kahana, Hagit Shani, Anat Grossman, Shirly Amar, Ginat Narkis, Lena Sagi-Dain, Lina Basel-Salmon, Idit Maya","doi":"10.1038/s10038-024-01252-7","DOIUrl":"10.1038/s10038-024-01252-7","url":null,"abstract":"Distal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance. We identified cases of distal Xq28 duplication (chrX: 154,126,575–154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication. Our search found 47 cases across 26 families, with duplications ranging from 208 to 935 Kb. In total, 8 out of 26 index cases featured a 200–300 kb partial duplication, mainly from Armenian/Caucasian Jewish backgrounds. Most prenatal cases showed no major fetal ultrasound malformations. Of cases with known inheritance mode (15 out of 26), maternal inheritance was more common (80%). The study identified seven male carriers of the duplication from six unrelated families, indicating partial penetrance in males. Our study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 7","pages":"337-343"},"PeriodicalIF":2.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s10038-024-01252-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7 小脑发育不全7（pontocellar hypoplasia 7）中核定位基序的TOE1变体的作用

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-04-11 DOI: 10.1038/s10038-024-01244-7

Yukiko Kuroda, Takuya Naruto, Yu Tsuyusaki, Ayumi Kato, Noriko Aida, Kenji Kurosawa

{"title":"Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7","authors":"Yukiko Kuroda, Takuya Naruto, Yu Tsuyusaki, Ayumi Kato, Noriko Aida, Kenji Kurosawa","doi":"10.1038/s10038-024-01244-7","DOIUrl":"10.1038/s10038-024-01244-7","url":null,"abstract":"Biallelic TOE1 variants can cause pontocerebellar hypoplasia type 7 (PCH7), a condition characterized by pontocerebellar hypoplasia with genital abnormality. TOE1 is a 3’-exonuclese for 3’-end maturation in small nuclear RNA. TOE1 pathogenic variants have been reported at the DEDD catalytic domain and zinc finger motif. Here, we describe a PCH7 patient with novel compound heterozygous TOE1 variants and a detailed clinical course. The patient was a 3-year-old female and showed developmental delay without cerebellar ataxic behavior. Head MRI revealed delayed myelination without pontocerebellar hypoplasia at 9 months of age. Progressive pontocerebellar atrophy was prominent at follow-up MRI. Cerebral abnormalities are characteristic features of PCH7 before pontocerebellar atrophy is observed. One variant, p.Arg331*, was located at the nuclear localization motif (NLM) and partially escaped from nonsense-mediated decay. This variant affected nuclear localization in mutant expressing cells, thus, the TOE1 variant at NLM leads to TOE1 dysfunction associated with nuclear mis-localization.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 7","pages":"349-355"},"PeriodicalIF":2.6,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590772","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

Long-term course of a case with a novel homozygous kyphoscoliosis peptidase variant 一个患有新型同卵脊柱后凸肽酶变异的病例的长期病理过程

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-04-08 DOI: 10.1038/s10038-024-01250-9

Yohei Misumi, Taro Yamashita, Aki Kuratomi, Yoshitaka Murakami, Atsushi Fujita, Naomichi Matsumoto, Mitsuharu Ueda

引用次数: 0

Heritability of complex traits in sub-populations experiencing bottlenecks and growth 经历瓶颈和增长的亚种群复杂性状的遗传率

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2024-04-08 DOI: 10.1038/s10038-024-01249-2

Cameron S. Taylor, Daniel J. Lawson

{"title":"Heritability of complex traits in sub-populations experiencing bottlenecks and growth","authors":"Cameron S. Taylor, Daniel J. Lawson","doi":"10.1038/s10038-024-01249-2","DOIUrl":"10.1038/s10038-024-01249-2","url":null,"abstract":"Populations that have experienced a bottleneck are regularly used in Genome Wide Association Studies (GWAS) to investigate variants associated with complex traits. It is generally understood that these isolated sub-populations may experience high frequency of otherwise rare variants with large effect size, and therefore provide a unique opportunity to study said trait. However, the demographic history of the population under investigation affects all SNPs that determine the complex trait genome-wide, changing its heritability and genetic architecture. We use a simulation based approach to identify the impact of the demographic processes of drift, expansion, and migration on the heritability of complex trait. We show that demography has considerable impact on complex traits. We then investigate the power to resolve heritability of complex traits in GWAS studies subjected to demographic effects. We find that demography is an important component for interpreting inference of complex traits and has a nuanced impact on the power of GWAS. We conclude that demographic histories need to be explicitly modelled to properly quantify the history of selection on a complex trait.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"69 7","pages":"329-335"},"PeriodicalIF":2.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s10038-024-01249-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0