‘Omics’ word of the day

Exposome: The collection of an individual’s environmental exposures over a lifetime.

HT: Christopher P. Wild in this article

Also see:
Wikipedia’s “omics” page
My CiteULike page (it’s RSS feed)

Viruses in the Genome

Carl Zimmer has an excellent post on viruses in the human genome.  Here is the juicy snip:

The human genome carries full-fledged retroviruses, as well as
viruses in various state of decay. Scientists have identified 98,000 of
these viruses, along with about 150,000 fragments of defunct viruses.
All told, they make up 8 percent of the human genome. In many cases,
the virus genes have disappeared altogether, leaving behind flanking
repeats, which have been duplicated to millions of copies that take up
about 40 percent of the genome. As a point of comparison, our "own"
genes–in other words, those that encode proteins that make up our
bodies and allow our bodies live–make up only about one percent of the

Some of these endogenous retroviruses are only found in some people
and not others. They must have invaded someone’s genome and then spread
to his or her descendants, but have not yet spread throug our entire
species. Others appear to be ubiquitous–meaning that they are ancient
passengers that had already spread throughout an ancestral population.

Read the whole piece.

Carl Zimmer, The Sixty-Million Year Virus. The Loom, March 13, 2006.

Norbert Bannert, and Reinhard Kurth. Retroelements and the human genome: new perspectives on an old relation. PNAS. October 5, 2004. vol. 101 (Suppl. 2) 14572-14579. [A nice open-access review article on human endogenous retroviruses (HERVS)]

Mexican HapMap Project

Mexico has launched its own genome project:

Mexico has launched a racebased genome project to determine if a genetic basis exists for its growing health crisis. The goal is to glean insights into genetic differences, believed to be unique to its population, that may play a key role in chronic diseases like asthma, diabetes and hypertension.

…The Instituto Nacional de Medicina Genomica (National Genomic Medicine Institute of Mexico, or INMEGEN) will manage the resulting ‘Mexican HapMap’…According to Gerardo Jimenez, director of INMEGEN and the new collaboration, INMEGEN will begin by sampling individuals in six remote regions of Mexico to construct a consensus genetic map that fits the entire Mexican mestizo population, a mixture of Europeans (mainly Spaniards) and Indians. The first objective is to determine if every block of nucleic acid sequence will be alike for all the Mexican groups. “My own prediction,” says Jimenez, “is that we are not going to find huge differences.”

INMEGEN will release newly mined genomic data into the public domain as fast as technology allows, but Jimenez is quick to point out that the measure of the project’s success is not the science, but rather the medicines that come out of it. He also envisions the initiative—the largest genotyping study ever launched in Latin America—having value beyond his country’s borders, informing public health research and drug discovery throughout mestizo countries. To that end, INMEGEN will seek alliances with other Latin American regions in the near future.

Stephen Herrera, Mexico launches bold genome project, Nature Biotechnology. September 2005. (sorry subscribers only) BUT see here!

INMEGEN homepage.

Resource: Brief Guide to SNPs

Applied Biosystems has published a brief guide to genetic markers.  This 10-page document provides a quick introduction to such things as restriction fragment length polymorphisms (RFLPs), short tandem repeats (STRs), single nucleotide polymorphisms (SNPs), and haplotypes.  Linkage and association studies are also briefly introduced.

Applied Biosystems. "SNPs — Powerful Tools for Association Studies" August 2003.

Modifier Genes vs. Susceptibility Genes

The identification of gene modifiers may improve our ability to understand differences in the severity of disease.  Having such information may help guide decisions about therapy, for both patients and doctors.  The outcomes of a search for gene modifiers for cystic fibrosis are described by one of the authors:

"There are likely a number of gene modifiers in CF and other diseases, and this current paper describes one of the first robust examples," [Michael] Knowles said. "Some CF patients may do worse because of ’severe inflammation’ genes, whereas others may do worse because of differences in mucus genes. Still others might because of their growth and metabolism genes, etc… Thus, therapy might need to be targeted to a particular area or areas in individual patients. This is important not only for CF, but for other lung diseases as well because gene modifiers we discover in CF will be seen in other diseases, and there are already examples of that."

An editorial accompanying the article in the New England Journal of Medicine describes how modifier genes are different from susceptibility genes:

"Susceptibility genes and modifier genes are two biologic phenomena that few clinicians should ignore in the genome era. Susceptibility genes, which are genes with functional variants that affect the causes of disease, are routinely being identified for simple mendelian diseases and, more recently, for common genetic disorders. Modifier genes are distinct from susceptibility genes, in that they are genetic variants that affect the clinical manifestation of disease (as opposed to liability)…The identification of gene modifiers and their interactions in cystic fibrosis and other diseases has only just begun."

Christina K. Haston and Thomas J. Hudson. "Finding Genetic Modifiers of Cystic Fibrosis" NEJM 353(14)1509-1511. October 6, 2005. (sorry subscribers only)

Drumm et al. "Genetic Modifiers of Lung Disease in Cystic Fibrosis" NEJM 353(14)1443-1453. October 6, 2005. (sorry subscribers only)

Genomiography: Large-Scale Copy Variations

Groups of scientists working independently have shown very large differences exist in the genomiography (i.e. genomic geography) of healthy individuals. These differences are much more dramatic than the well-known single nucleotide kind of variation, SNPs. Dr. Stephen Scherer, co-principal investigator, senior scientist at Sick Kids, and associate professor at University of Toronto describes the discovery:

“Using new genome scanning technologies, we serendipitously found stretches of DNA sometimes hundreds of thousands of chemical bases (nucleotides) long that were present or absent in the genomes of healthy individuals. These large-scale copy variations, or LCVs, frequently overlap with genes and could explain why people are different…At first we were astonished and didn’t believe our results because for years we had been taught that most variation in DNA was limited to very small changes. Then we heard the Harvard group was making similar observations and ultimately we combined our data and came to the same conclusion.”

Dr. Charles Lee
, the other co-principal investigator and assistant prof at Harvard Medical School gives his take on the discovery:

“Because these newly discovered variants exist in the genomes of healthy individuals, their presence could lead to subtle differences affecting physical or behavioural traits by influencing the expression of specific genes, but they could also predispose to future disease…For example, the most common LCV involves amylase genes. Our study shows that some people may have 10 copies of this gene while others may have as much as 24 copies of this same gene. It would be really exciting if we found that an increased copy number of these genes was associated with increased susceptibility to pancreatic diseases or cancer. This would allow us to use these LCVs as disease markers.”

The press release at EurekaAlert! puts the discovery into perspective:

Early information from the Human Genome Project indicated that the DNA in the genome of any two individuals is 99.9 per cent identical with the 0.1 per cent variation arising primarily from some three million single nucleotide changes scattered amongst the chromosomes. The new data from the Sick Kids and Harvard groups revealed 255 regions (comprising more than 0.1 per cent) of the genome where large chunks of DNA are present in different copy numbers between individuals. Over 50 per cent of these alterations lead to changes in gene numbers and at least 14 regions overlapped with known sites associated with human disease.

These groups have put their data in publicly available database entitled the Database of Genomic Variants: A curated catalogue of large-scale variation in the human genome.

Primary Sources:

Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525-528 (July 23, 2004).

Iafrate, A.J. et al. Detection of large-scale variation in the human genome. Published online in Nature Genetics August 1, 2004.

Kate Ruder, Large-Scale Differences Discovered in DNA of Healthy People. Genome News Network, August 6, 2004.

DNA variations surprise researchers
. EurakaAlert! August 1, 2004.

UPDATE: Genomiography promises to be a googlewhackblatt if only for a very short time. I suspect phylogenomiography will be a googlewhackblatt for much longer.