Esta página ha sido traducida por una máquina. Otras páginas pueden seguir apareciendo en inglés. View in English

Mapeo fino endógeno y priorización de los elementos reguladores funcionales en los loci genéticos complejos

Ke Zhao ¹, Yao Zhou ², Xueqi Wang ³

¹Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Center for Public Health Laboratory Testing, School of Public Health, Shandong Second Medical University, Weifang, Shandong, China.
²Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
³State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
⁴Oujiang Laboratory, Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
⁵Department of Gynecology, Women and Children's Hospital of Ningbo University, Zhejiang, China.
⁶Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
⁷Centre for PanorOmic Sciences-Genomics and Bioinformatics Cores, The University of Hong Kong, Hong Kong, China.
⁸Department of Epidemiology and Biostatistics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
⁹Zhejiang Engineering Research Center for Intelligent Manufacturing of Clinical Diagnostic Equipment, Hangzhou, China.
¹⁰Program in Bioinformatics, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
¹¹Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
¹²Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, Center for Cardiovascular Diseases, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

⁰Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Center for Public Health Laboratory Testing, School of Public Health, Shandong Second Medical University, Weifang, Shandong, China.

Cell Genomics +

|

29 de agosto de 2025

Ver abstracta en PubMed

Resumen

La mayoría de las causas genéticas de los rasgos complejos están ocultas en el ADN no codificante. Este estudio revela múltiples elementos reguladores en el desequilibrio de enlace perfecto (pLD) que afectan la expresión génica, descubriendo mecanismos genéticos previamente ocultos.

Área De La Ciencia

La genómica
Biología molecular
La epigenética

Sus Antecedentes

Los loci genéticos para los rasgos poligénicos a menudo residen en regiones no codificantes.
La regulación compleja y el desequilibrio de enlace (LD) dificultan la identificación de la variante causal y el gen.

Objetivo Del Estudio

Investigar las relaciones entre el elemento cis-regulador (CRE) y la expresión génica dentro de la DL estrecha.
Descubrir efectos genéticos de grano fino en la expresión génica difíciles de descifrar con métodos tradicionales.

Principales Métodos

Interferencia CRISPR de una sola célula multiplexada y perturbaciones de activación.
Análisis del contexto endógeno de la cromatina y datos epigenéticos y de secuencia de células multiomas.

Principales Resultados

Prevalencia demostrada de la causalidad múltiple en el LD perfecto (pLD) para los loci de rasgos cuantitativos de expresión independiente (eQTL).
Efectos genéticos de grano fino identificados en la expresión génica dentro de la pLD.
Se encontró que más de un tercio de las ERC causales carecen de marcadores epigenéticos clásicos antes de la perturbación.
Funcionalmente validado un mecanismo de regulación oculto.

Conclusiones

Destacando la plasticidad reguladora del genoma humano.
Exploración orientadora de los mecanismos causales en la regulación de los rasgos moleculares y el desarrollo de la enfermedad.

Palabras clave:

CRISPR y sus derivados Perturb-seq es el nombre que se le da a la eQTL (en inglés) desequilibrio de enlace Elemento normativo

Videos de Conceptos Relacionados

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...