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Evolutionary origin of germline pathogenic variants in human DNA mismatch repair genes.
Lei, Huijun; Li, Jiaheng; Zhao, Bojin; Kou, Si Hoi; Xiao, Fengxia; Chen, Tianhui; Wang, San Ming.
Afiliación
  • Lei H; Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
  • Li J; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China.
  • Zhao B; Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.
  • Kou SH; Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
  • Xiao F; Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
  • Chen T; Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
  • Wang SM; Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
Hum Genomics ; 18(1): 5, 2024 Jan 29.
Article en En | MEDLINE | ID: mdl-38287404
ABSTRACT

BACKGROUND:

Mismatch repair (MMR) system is evolutionarily conserved for genome stability maintenance. Germline pathogenic variants (PVs) in MMR genes that lead to MMR functional deficiency are associated with high cancer risk. Knowing the evolutionary origin of germline PVs in human MMR genes will facilitate understanding the biological base of MMR deficiency in cancer. However, systematic knowledge is lacking to address the issue. In this study, we performed a comprehensive analysis to know the evolutionary origin of human MMR PVs.

METHODS:

We retrieved MMR gene variants from the ClinVar database. The genomes of 100 vertebrates were collected from the UCSC genome browser and ancient human sequencing data were obtained through comprehensive data mining. Cross-species conservation analysis was performed based on the phylogenetic relationship among 100 vertebrates. Rescaled ancient sequencing data were used to perform variant calling for archeological analysis.

RESULTS:

Using the phylogenetic approach, we traced the 3369 MMR PVs identified in modern humans in 99 non-human vertebrate genomes but found no evidence for cross-species conservation as the source for human MMR PVs. Using the archeological approach, we searched the human MMR PVs in over 5000 ancient human genomes dated from 45,045 to 100 years before present and identified a group of MMR PVs shared between modern and ancient humans mostly within 10,000 years with similar quantitative patterns.

CONCLUSION:

Our study reveals that MMR PVs in modern humans were arisen within the recent human evolutionary history.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Neoplásicos Hereditarios / Neoplasias Encefálicas / Neoplasias Colorrectales / Reparación de la Incompatibilidad de ADN Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Neoplásicos Hereditarios / Neoplasias Encefálicas / Neoplasias Colorrectales / Reparación de la Incompatibilidad de ADN Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido