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.

Education: Six Weeks to Genomic Awareness

Around 6 hours of streaming lectures entitled, "Six Weeks to Genomics Awareness" are available here.  This lecture series was created by the University of Michigan Center for Genomics and Public Health and other collaborators.

Here are the lecture topics:
Module 1, Introduction to Genomics, Part 1: The Human Genome
Module 1, Introduction to Genomics, Part 2: Genes in Their Cellular Context
Module 1, Introduction to Genomics, Part 3: Genetic Mutation
Module 1, Introduction to Genomics, Part 4: Pedigree Analysis
Module 2, Genes in Populations, Part 1: Population Genetic Perspectives
Module 2, Genes in Populations, Part 2: Genotype-Phenotype Relationships
Module 3, Genetic Testing, Part 1: What is Genetic Testing?
Module 3, Genetic Testing, Part 2: The Challenges
Module 4, Gene-Environment Interactions, Part 1: Definitions and Examples
Module 4, Gene-Environment Interactions, Part 2: Pharmacogenetics
Module 5: Ethical, Legal and Social Issues
Module 6: An Overview ofState and National Resources

Myriad DTC Genetics Marketing

Between September 2002 and February 2003 a genetic test was marketed direct-to-consumer (DTC) by Myriad Genetics, perhaps the first legitimate medical genetic test to go DTC.  The ad campaign by Myriad was for BRCAnalysis, a genetic test measuring risk for breast and ovarian cancer based on the presence/absence of mutations in specific genes.  The campaign aired in only two cities, Denver and Atlanta.

A recent Business Week article describes Myriad’s campaign as well as a follow-up study conducted by the CDC assessing it’s impact on consumer behavior in the test markets.  The CDC report provides the following summary of these results:

"consumer and provider awareness of BRCA1/2 testing increased in the pilot cities and… providers in these cities perceived an impact on their practice (e.g., more questions asked about testing, more BRCA1/2 tests requested, and more tests ordered)."

So far so good.  Then the authors of the CDC study continue:

"However, in all four cities, providers often lacked knowledge to advise patients about inherited BOC and testing. These findings underscore the need for evidence-based recommendations on appropriate use of genetic tests and education of providers and the public to achieve maximum individual and public health benefit from genetic testing."

Indeed, there are only about 400 genetic counselors in the U.S. that specialize in cancer genetic counseling.  A napkin sketch of the numbers…approx. 290 million U.S. population, 150 million female population, say 1% of the female population are candidates for genetic testing for breast cancer, then roughly 1.5 million women are potentially in need of genetic counseling at some point for this test.

How about virtual genetic counseling?  Probably not for everyone, but likely to get much much better (and much much more popular?).  A recent EurekaAlert public release describes a recent study of virtual genetic counseling for breast cancer:

An interactive computer program developed at Penn State College of Medicine is as effective as one-on-one genetic counseling for increasing knowledge of breast cancer and genetic testing among women at low risk for breast cancer…Counselors were, however, more effective than the computer program at reducing women’s anxiety and helping them to more clearly understand their risk.

"’These results suggest that the computer program has the potential to stand alone as an educational intervention for low-risk women, but should be used in combination with one-on-one genetic counseling for women at high risk,’ said Michael J. Green, M.D., M.S., associate professor of humanities and medicine, Penn State College of Medicine. ‘The computer program is an alternative means of communicating information about genetic testing and may help women without access to genetic counselors to decide whether or not to have genetic testing for susceptibility to breast cancer.’"

How will personal genomics change the nature of genetic testing?  Currently, a person may go to their doctor or genetic counselor to discuss the availability, accuracy, and helpfulness of genetic tests for a specific disease that is prevalent in their family.  This person may decide to go ahead with the test; a buccal swab is taken and sent to a lab; several weeks pass and the patient and doctor meet again to discuss the results.  In the future, a person might need only to jump online, access their genome (which is attached to their electronic medical record), and click-through a virtual test since the genome sequence is already known.  Educational materials and virtual counseling are available throughout this online experience.  For those who desire face-to-face counseling (including the possibility of video webchat), an appointment can be made online at any time.

Amy Tsao. Genetic Testing Meet Mad Ave. Business Week.  July 28, 2004.

Jacobellis, J. et al. Genetic Testing for Breast and Ovarian Cancer Susceptibility: Evaluating Direct-to-Consumer Marketing — Atlanta, Denver, Raleigh-Durham, and Seattle, 2003.  MMWR weekly. 53(27):603-606 July 16, 2004.

The press release announcing the DTC campaing for BRCAnalysis by Myriad Genetics.

Press Release. Virtual counselor supplements traditional genetic counseling. EurekaAlert. July 27 2004.

Green MJ et al. Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial. JAMA 292(4):496-8.

Other Resources:
National Cancer Institute on Breast Cancer

National Cancer Institute on Ovarian Cancer

Myriad Genetics on Ovarian and Breast Cancer