Geneimprint
5 December 2025: Francis Crick, James Watson, and Maurice Wilkins won the 1962 Nobel Prize in Physiology or Medicine for their discovery of the double-helix structure of DNA. Sadly, the last of these Nobel laureates, James D. Watson, died November 6, 2025 in East Northport, New York at the age of 97 (AACR Memoriam).
The seminal paper by Watson and Crick that subsequently enabled scientists to unravel the mechanisms of genetic inheritance and cellular protein synthesis, and ultimately the complete human genome (Venter et al., 2001) and (Lander et al., 2001) was simply entitled, Molecular structure of nucleic acids; structure for deoxyribose nucleic acid (Watson and Crick, 1953).
On the fiftieth anniversary of the publication of this seminal paper, Waterland and Jirtle (2003) provided the first evidence that the developmental origins of health and disease (DOHaD) result from alterations in the epigenome - the genetic programs that tell the cells when, where and how to work. Importantly, our ground breaking Agouti Mouse Study was also featured on the streamed companion to the PBS episode entitled, The Secret of Life because it demonstrated, for first time, why "Genes don't code for everything!"
The autographs of Watson and Jirtle on the historical photo above visually attest to the fact that the genome and epigenome function in concert to bring life into being, and that both play critical roles in the genesis of human health and disease.
The monoallelic parent-of-origin dependent expression of imprinted genes is regulated by differentially methylated imprint control regions (ICRs) - the human imprintome. The epigenetic dysregulation of the imprintome by environmental exposures during early development results in the fetal origins of behavioral disorders and common chronic diseases. Whole genome bisulfite sequencing (WGBS) is a unique method to profile these ICRs (Cevik, et. al. 2024); however, it is computationally intensive since it requires high coverage, making it expense for use in large epidemiological studies. Read more...
Using WGBS and the recently identified human imprintome (Jima et al., 2022), we provide the first evidence that DNA methylation in 120 candidate imprint control regions (ICRs) varies markedly in the brains of people with Alzheimer's disease (AD) versus that in controls (Cevik et al., 2024). Read more...
In 1953 Watson and Crick determined the structure of DNA. Fifty years later Waterland and Jirtle demonstrated with the Agouti Mouse Study that the fetal origins of adult disease susceptibility results from alterations in the epigenome - the genetic programs that tell the genes when, where and how to work. Thus, not only mutations in the genome, but also changes in the epigenome function in the genesis of human health and disease. Read more...
Genomic imprinting is a unique epigenetic form of gene regulation that evolved in marsupials and placental mammals about 150 million years ago (Imprinting Evolution in Mammals). It results in only one copy of a gene being expressed in a parent-of-origin dependent manner. Thus, imprinted genes are disease susceptibility loci since a single genetic or epigenetic event can alter their function.
Imprinted genes are heavily involved in metabolism and growth regulation. An epigenetic tug-of-war between the mothers and fathers imprinted genes during development has been postulated to explain variations in the fetal origins of metabolic disorders such as obesity and type 2 diabetes, as well as cancer, and a spectrum of mental disorders ranging from autism to schizophrenia (Badcock and Crespi, 2008). Read more...
We previously predicted and experimentally demonstrated that KCNK9 is imprinted in humans, and maternally expressed in the brain (Luedi et al, 2007). We now show that KCNK9 is also expressed only from the maternal allele in breast epithelium, and that loss of imprinting at this locus is linked to the pathogenesis of triple negative breast cancer (TNBC) (Skaar et al, 2021).
Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein. It is overexpressed in 40% of breast cancer; however, gene amplification accounts for increased expression in less than 10% of these cancers. Read more...
