Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




Inherited Causes of Clonal Hematopoiesis in Multiplicity of Whole Genomes

By LabMedica International staff writers
Posted on 29 Oct 2020
The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating hematopoietic stem cell populations has recently been associated with both hematological cancer and coronary heart disease, and this phenomenon is termed clonal hematopoiesis of indeterminate potential (CHIP). More...


As the name CHIP suggests, this subpopulation in the blood is characterized by a shared unique mutation in the cells' DNA; it is thought that this subpopulation is "clonally" derived from a single founding cell and is therefore made of genetic "clones" of the founder. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP.

A team of scientists at the Broad Institute (Cambridge, MA, USA) and their colleagues analyzed high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. They noted that the prevalence of CHIP increased with the age at which the blood samples were taken from participants, as well as with a history of smoking.

The investigators identified associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. About three-quarters of individuals with CHIP had mutations in just three genes: DNMT3A, TET2, and ASXL1. Some CHIP characteristics, they noted, varied by driver gene mutation. For instance, JAK2 CHIP mutation carriers were generally younger than other carriers, and TET2 CHIP carriers tended to have increased interleukin-1β (IL-1β levels), while JAK2 and SF3B1 carriers had increased circulating IL-18.

Within a subset of this cohort, the team conducted a single-variant genome-wide association analysis to uncover germline variants linked to CHIP. Through their analysis and subsequent replication, they uncovered one variant in TERT that was associated with a 1.3-fold increased risk of developing CHIP, as well as a variant near both KPNA4 and TRIM59 that was associated with a 1.16-fold increased risk and a variant near TET2 that was associated with a 2.4-fold increased risk of developing CHIP.

The authors concluded that germline genetic variation shapes hematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal hematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues. The study was published on October 14, 2020 in the journal Nature.

Related Links:
Broad Institute


Gold Member
Blood Gas Analyzer
Stat Profile pHOx
Portable Electronic Pipette
Mini 96
New
Gold Member
Hematology Analyzer
Medonic M32B
Autoimmune Disease Diagnostic
Chorus ds-DNA-G
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Hematology

view channel
Image: New research points to protecting blood during radiation therapy (Photo courtesy of 123RF)

Pioneering Model Measures Radiation Exposure in Blood for Precise Cancer Treatments

Scientists have long focused on protecting organs near tumors during radiotherapy, but blood — a vital, circulating tissue — has largely been excluded from dose calculations. Each blood cell passing through... Read more

Immunology

view channel
Image: The VENTANA HER2 (4B5) test is now CE-IVDR approved (Photo courtesy of Roche)

Companion Diagnostic Test Identifies HER2-Ultralow Breast Cancer and Biliary Tract Cancer Patients

Breast cancer is the most common cancer in Europe, with more than 564,000 new cases and 145,000 deaths annually. Metastatic breast cancer is rising in younger populations and remains the leading cause... Read more

Technology

view channel
Image: Conceptual design of the CORAL capsule for microbial sampling in the small intestine (H. Mohammed et al., Device (2025). DOI: 10.1016/j.device.2025.100904)

Coral-Inspired Capsule Samples Hidden Bacteria from Small Intestine

The gut microbiome has been linked to conditions ranging from immune disorders to mental health, yet conventional stool tests often fail to capture bacterial populations in the small intestine.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.