The
“switching on” or expression of specific genes in the human genome is
what makes each human tissue and each human being unique. A new study by
researchers at the Johns Hopkins Bloomberg School of Public Health, the
Lieber Institute for Brain Development, and the National Institute of
Mental Health found that many gene expression changes that occur during
fetal development are reversed immediately after birth. Reversals of
fetal expression changes are also seen again much later in life during
normal aging of the brain.
Global comparison of genetic and transcriptional differences between subjects. Each point represents a comparison of two subjects in the collection. |
Additionally,
the team observed the reversal of fetal expression changes in
Alzheimer’s disease findings reported in other studies. The research
team also found that gene expression change is fastest in human brain
tissue during fetal development, slows down through childhood and
adolescence, stabilizes in adulthood, and then speeds up again after age
50, with distinct redirection of expression changes prior to birth and
in early adulthood. Their findings are published in the October 27,
2011, edition of Nature. All of the data are available to the public as a
web-based resource at: www.libd.org/braincloud.
Using
a number of genomic analysis technologies, the research team conducted
genome-wide genetic (DNA) and gene expression (RNA) analyses of brain
tissue samples from the prefrontal cortex. Tissue represented the
various stages of the human lifespan.
“We
think that these coordinated changes in gene expression connecting
fetal development with aging and neurodegeneration are central to how
the genome constructs the human brain and how the brain ages,” said
Carlo Colantuoni, PhD, one of the lead authors of the study and a former
research associate with the Department of Biostatistics at the Johns
Hopkins Bloomberg School of Public Health. Colantuoni recently joined
the Lieber Institute for Brain Development on the Johns Hopkins Medical
Campus.
The
research also showed that brain gene expression differences between
genetically diverse individuals (of different races, for example) are no
greater than the differences between individuals sharing many more
genetic traits.
“Our
findings highlight the fact that current technologies and analysis
methods can address the effects of individual genetic traits in
isolation, but we have virtually no understanding of how our many
millions of genetic traits work in concert with one another,” added
Colantuoni.
Funding
for the research was provided by the Lieber Institute for Brain
Development, Baltimore, Maryland USA and the Intramural Research Program
in the National Institute of Mental Health, National Institutes of
Health.
Temporal Dynamics and Genetic Control of Transcription in Human Prefontal Cortex
