Nature Reviews Genetics最新文献_第9页

Human embryonic genetic mosaicism and its effects on development and disease 人类胚胎基因嵌合及其对发育和疾病的影响

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-04-11 DOI: 10.1038/s41576-024-00715-z

Sarah M. Waldvogel, Jennifer E. Posey, Margaret A. Goodell

{"title":"Human embryonic genetic mosaicism and its effects on development and disease","authors":"Sarah M. Waldvogel, Jennifer E. Posey, Margaret A. Goodell","doi":"10.1038/s41576-024-00715-z","DOIUrl":"10.1038/s41576-024-00715-z","url":null,"abstract":"Nearly every mammalian cell division is accompanied by a mutational event that becomes fixed in a daughter cell. When carried forward to additional cell progeny, a clone of variant cells can emerge. As a result, mammals are complex mosaics of clones that are genetically distinct from one another. Recent high-throughput sequencing studies have revealed that mosaicism is common, clone sizes often increase with age and specific variants can affect tissue function and disease development. Variants that are acquired during early embryogenesis are shared by multiple cell types and can affect numerous tissues. Within tissues, variant clones compete, which can result in their expansion or elimination. Embryonic mosaicism has clinical implications for genetic disease severity and transmission but is likely an under-recognized phenomenon. To better understand its implications for mosaic individuals, it is essential to leverage research tools that can elucidate the mechanisms by which expanded embryonic variants influence development and disease. Genetic variants acquired early during embryogenesis can affect numerous tissues. The authors review the phenomenon of embryonic mosaicism, with a focus on small variants, and discuss mechanisms of cell competition that allow mosaic clones to expand, as well as the functional consequences of mosaicism for embryo viability and the health of the organism.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 10","pages":"698-714"},"PeriodicalIF":39.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pleiotropy, epistasis and the genetic architecture of quantitative traits 多效性、外显性和数量性状的遗传结构

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-04-02 DOI: 10.1038/s41576-024-00711-3

Trudy F. C. Mackay, Robert R. H. Anholt

{"title":"Pleiotropy, epistasis and the genetic architecture of quantitative traits","authors":"Trudy F. C. Mackay, Robert R. H. Anholt","doi":"10.1038/s41576-024-00711-3","DOIUrl":"10.1038/s41576-024-00711-3","url":null,"abstract":"Pleiotropy (whereby one genetic polymorphism affects multiple traits) and epistasis (whereby non-linear interactions between genetic polymorphisms affect the same trait) are fundamental aspects of the genetic architecture of quantitative traits. Recent advances in the ability to characterize the effects of polymorphic variants on molecular and organismal phenotypes in human and model organism populations have revealed the prevalence of pleiotropy and unexpected shared molecular genetic bases among quantitative traits, including diseases. By contrast, epistasis is common between polymorphic loci associated with quantitative traits in model organisms, such that alleles at one locus have different effects in different genetic backgrounds, but is rarely observed for human quantitative traits and common diseases. Here, we review the concepts and recent inferences about pleiotropy and epistasis, and discuss factors that contribute to similarities and differences between the genetic architecture of quantitative traits in model organisms and humans. In this Review, Mackay and Anholt discuss how epistasis and pleiotropy contribute to the genetic architecture of quantitative traits and outline factors that might explain observed differences in their prevalence between model organisms and humans.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 9","pages":"639-657"},"PeriodicalIF":39.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 variation across and within individuals 个体间和个体内的遗传变异

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-28 DOI: 10.1038/s41576-024-00709-x

Zhi Yu, Tim H. H. Coorens, Md Mesbah Uddin, Kristin G. Ardlie, Niall Lennon, Pradeep Natarajan

{"title":"Genetic variation across and within individuals","authors":"Zhi Yu, Tim H. H. Coorens, Md Mesbah Uddin, Kristin G. Ardlie, Niall Lennon, Pradeep Natarajan","doi":"10.1038/s41576-024-00709-x","DOIUrl":"10.1038/s41576-024-00709-x","url":null,"abstract":"Germline variation and somatic mutation are intricately connected and together shape human traits and disease risks. Germline variants are present from conception, but they vary between individuals and accumulate over generations. By contrast, somatic mutations accumulate throughout life in a mosaic manner within an individual due to intrinsic and extrinsic sources of mutations and selection pressures acting on cells. Recent advancements, such as improved detection methods and increased resources for association studies, have drastically expanded our ability to investigate germline and somatic genetic variation and compare underlying mutational processes. A better understanding of the similarities and differences in the types, rates and patterns of germline and somatic variants, as well as their interplay, will help elucidate the mechanisms underlying their distinct yet interlinked roles in human health and biology. In this Review, the authors compare the characteristics and detection methods of germline and somatic variants. Furthermore, they outline how the interplay between the two types of genetic variation can affect human health.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"548-562"},"PeriodicalIF":39.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140310800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Building a catalogue of short tandem repeats in diverse populations 建立不同人群的短串联重复序列目录。

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-27 DOI: 10.1038/s41576-024-00726-w

Ning Xie

引用次数: 0

AIRE targets poised promoters enriched for Z-DNA AIRE 以富含 Z-DNA 的定向启动子为目标。

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-27 DOI: 10.1038/s41576-024-00728-8

Kirsty Minton

引用次数: 0

Global genomic diversity for All of Us 我们所有人的全球基因组多样性

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-20 DOI: 10.1038/s41576-024-00727-9

Linda Koch

引用次数: 0

The evolution of modifier genes 修饰基因的演变

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-19 DOI: 10.1038/s41576-024-00724-y

Yoav Ram

引用次数: 0

Dynamics of ER stress-induced gene regulation in plants 植物中ER胁迫诱导的基因调控动态。

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-18 DOI: 10.1038/s41576-024-00710-4

Dae Kwan Ko, Federica Brandizzi

{"title":"Dynamics of ER stress-induced gene regulation in plants","authors":"Dae Kwan Ko, Federica Brandizzi","doi":"10.1038/s41576-024-00710-4","DOIUrl":"10.1038/s41576-024-00710-4","url":null,"abstract":"Endoplasmic reticulum (ER) stress is a potentially lethal condition that is induced by the abnormal accumulation of unfolded or misfolded secretory proteins in the ER. In eukaryotes, ER stress is managed by the unfolded protein response (UPR) through a tightly regulated, yet highly dynamic, reprogramming of gene transcription. Although the core principles of the UPR are similar across eukaryotes, unique features of the plant UPR reflect the adaptability of plants to their ever-changing environments and the need to balance the demands of growth and development with the response to environmental stressors. The past decades have seen notable progress in understanding the mechanisms underlying ER stress sensing and signalling transduction pathways, implicating the UPR in the effects of physiological and induced ER stress on plant growth and crop yield. Facilitated by sequencing technologies and advances in genetic and genomic resources, recent efforts have driven the discovery of transcriptional regulators and elucidated the mechanisms that mediate the dynamic and precise gene regulation in response to ER stress at the systems level. Plants have uniquely adapted to manage endoplasmic reticulum stress triggered by protein misfolding. The authors review the dynamics of gene expression regulation underlying the unfolded protein response in plants, highlighting recent insights provided by systems-level approaches and omics data.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"513-525"},"PeriodicalIF":42.7,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Competition between sites of meiotic recombination in snakes 蛇类减数分裂重组位点之间的竞争。

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-12 DOI: 10.1038/s41576-024-00722-0

Kirsty Minton

引用次数: 0

The regulatory landscape of chromatin accessibility 染色质可及性的调控格局

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-03-11 DOI: 10.1038/s41576-024-00719-9

Henry Ertl

引用次数: 0