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人类端粒长度具有染色体末端特异性,且在个体间保持保守。

Human telomere length is chromosome end-specific and conserved across individuals.

作者信息

Karimian Kayarash, Groot Aljona, Huso Vienna, Kahidi Ramin, Tan Kar-Tong, Sholes Samantha, Keener Rebecca, McDyer John F, Alder Jonathan K, Li Heng, Rechtsteiner Andreas, Greider Carol W

机构信息

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

Science. 2024 May 3;384(6695):533-539. doi: 10.1126/science.ado0431. Epub 2024 Apr 11.

Abstract

Short telomeres cause age-related disease, and long telomeres contribute to cancer; however, the mechanisms regulating telomere length are unclear. We developed a nanopore-based method, which we call Telomere Profiling, to determine telomere length at nearly single-nucleotide resolution. Mapping telomere reads to chromosome ends showed chromosome end-specific length distributions that could differ by more than six kilobases. Examination of telomere lengths in 147 individuals revealed that certain chromosome ends were consistently longer or shorter. The same rank order was found in newborn cord blood, suggesting that telomere length is determined at birth and that chromosome end-specific telomere length differences are maintained as telomeres shorten with age. Telomere Profiling makes precision investigation of telomere length widely accessible for laboratory, clinical, and drug discovery efforts and will allow deeper insights into telomere biology.

摘要

短端粒会引发与年龄相关的疾病,而长端粒则会促使癌症发生;然而,调节端粒长度的机制尚不清楚。我们开发了一种基于纳米孔的方法,称之为端粒分析,以近乎单核苷酸分辨率来测定端粒长度。将端粒读数映射到染色体末端显示出特定于染色体末端的长度分布,这些分布可能相差超过6千碱基。对147名个体的端粒长度进行检测发现,某些染色体末端始终较长或较短。在新生儿脐带血中也发现了相同的排序,这表明端粒长度在出生时就已确定,并且随着端粒随年龄缩短,特定于染色体末端的端粒长度差异会得以维持。端粒分析使端粒长度的精确研究能够广泛应用于实验室、临床和药物研发工作中,并将有助于更深入地了解端粒生物学。

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