Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mutat Res. 2002 Aug 29;505(1-2):27-41.

Mutational spectral analysis at the HPRT locus in healthy children.

Author information

  • 1Department of Pediatrics, University of Vermont, Burlington 05405, USA. finette@salus.med.uvm.edu

Abstract

There is growing evidence linking somatic mutational events during fetal development and childhood to an increasing number of multifactorial human diseases. Despite this, little is known about the relationship between endogenous and environmentally induced exogenous mutations during human development. Here we describe a comparative spectral analysis of somatic mutations at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene locus in healthy children. We observed an age-specific decrease in the proportion of large alterations and a corresponding increase in the proportion of small alterations with increasing age following birth (P<0.001). The age specific decrease in the proportion of large alterations (67-30%) was mainly due to a decrease in the proportion of aberrant variable (V), diversity (D) and joining (J) (V(D)J) recombinase mediated HPRT deletions (P<0.001). The increase in the proportion of small alterations with age (28-64%) was associated with an increase in transversions from 8% in children at the late stages of fetal development to 31% in children 12-16 years old (P=0.003). Transitions decreased with age, especially at CpG dinucleotides (P=0.010), as transversions increased (P=0.009). These patterns of mutations provide insight into important spontaneous, genotoxic, and site-specific recombinational somatic mutational events associated with the age-specific development of human disease in children as well as adults.

PMID:
12175903
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk