Tag Archives: human genome

Breaking the Human Genome Code

On one hand side we are able to sequence anyone’s genome cheaply and quickly due to latest technologies. On the other hand side we are at the beginning to discover the true meaning of individual genomes. This is the reason why the lecture has the subline “Opening Pandora’s Box”.

Professor Winston Hide talks about newly arising questions such as:

  • If you have your genome sequenced, who should see it?
  • How can we safely share a genome without ending up opening a whole new form of cybersnooping?
  • How could the new technologies be used to predict a person’s predisposition for Alzheimer’s, Parkinson’s or motor neurone disease?

Whole genome sequencing a complete island



Two days ago a groundbreaking study was published in Nature Genetics: Whole genome sequencing of 2,636 Icelanders and Genotyping of 104,220 Icelanders.

The advantage of using a small population like the Icelanders for this kind of study is that there are fewer rare variants, but sometimes also a higher occurance of some of these variants.

For the study, geenomic DNA was isolated from white blood cells and subsequent sequencing was performed on GAIIx and HiSeq instruments. The resulting reads were aligned to the human reference genome (NCBI Build 36 (hg18).

Gudbjartsson et al. then examined the data from different angles. For example, they looked for geographical dependencies for specific variants or how the data can be used to learn more about phenotypes and their underlying genomic pattern. But they also report an example “how rare variants […] can be used to analyze clinical problems”. (Gudbjartsson et. al)

Since every human being has a unique genomic pattern I think studies like this are of high importance to learn more about disease related genotypes. This will help to gain confidence in the results that we get from molecular diagnostic assays for disease treatment now and in the future.

Read the complete publication here.

Prepare NGS for clinical use

Molecular diagnostics (MDx) is to my opinion the most sensitive application for all kinds of molecular biology techniques like PCR, Sanger Sequencing or Next Generation Sequencing. Today, NGS is still a niche application and needs further improvement to be a common tool for MDx. One thing that is lacking is the standardisation of NGS for clinical use.

The NGS Working Group, established by the Friends of Cancer Research worked out a master plan (The ASCO Post), with critical points that need to be addressed to use NGS more commonly:

1. Define a regulatory pathway for cancer panels (a selection of multimarker gene assays) intended to identify actionable oncogenic alterations (those with supporting data to create risk-benefit assessment of treatment choice) that allow flexibility in the appropriate FDA medical device pathway—for instance, one based on risk classification of different panel components depending on the specific marker.

2. Approaches to validation studies should be based on the types of alterations measured by the assay rather than on every alteration individually.

3. Determine the contents of a cancer panel by classifying potential markers based on current utility in clinical care and clinical trials and peer-reviewed publications, as well as recognized clinical guidelines. Draw upon various sources to determine the recommended marker set for an actionable cancer panel.

4. Promote standardization of cancer panels through development and use of a common set of samples to ensure reproducibility on each platform.

5. Establish a framework for determining an appropriate reference method rather than relying on any single method for all studies.

Get more information to each proposal here.

Think Big: The UK 100,000 Genome Project

In late 2012 the 100,000 genome project was launched. UK Prime Minister David Cameron announced a new initiative led by the National Health Service to sequence the genomes of up to 100,000 people and to use their genomic information in treatment and studies of cancer and other diseases. The government set aside 100 million GBP for this project.

hiseq-x-tenGenomics England which is heading the project now named 10 firms that have been selected to for the assessment of the next phase of the project. The companies are Congenica; Diploid; NantOmics; Genomics Ltd.; Illumina; Qiagen; Lockheed Martin; NextCode Health; Omicia; and Personalis.

As part of the recently completed stage, Genomics England in February sent out a questionnaire to 28 participants in relation to 10 cancer/normal samples and 15 rare disease trio samples.

Illumina is partnering as well and will contribute with the ultra-high throughput sequencing platform HiSeq XTM Ten.

What will be the next step? Sequencing everyone?

Do you want to share your biggest secret?

people_09Should we all get our genome sequenced? And share the information? Just today I read two articles in GenomeWeb regarding human genome sequencing. With, to my opinion, opposite views regarding sharing information from human genomes.

The first article is about the 23andMe project: Here two different groups of people said, that with the functionality “check for close relatives” box they ended up in real crisis in their family. In one case the parents divorced since the close relative box showed that the husband had already a child with another women (prior this marriage). And in the other case a girl found out that she has a brother, whom her mother has giving up for adoption.

So for me this is a clear indicator that simply sharing the genome information might really cause more problems than it can solve.

Exactly the opposite is asked for by George Church. From his point of view for eradicating diseases, creating unlimited energy sources and so on a public access to as many genomes (human and non-human) as possible is a prerequisite.

And I think I could agree to that partially, if we talk about bacteria or plant genomes. But I think we are not ready for a wide sharing of human genome information.

What also became clear to me is that we are not a lot further, than 2 years ago (Genomics – A Curse Or A Blessing?).

Unexpected Heroes

Image courtesy of FreeDigitalPhotos.netThere are several mutations known which are linked to childhood diseases. This knowledge is already being used e.g. to analyze genomes of sick newborns for any known diseases, or for prenatal diagnostics. However: A person carrying such a mutation must not necessarily get ill.

Some individuals carry a mutation that should have caused a severe disease in their childhood. However, some yet unknown factors have protected them from getting ill. Even though they may be very rare, studying such persons may help to understand more about the diseases, or even find new treatments.

Researchers of the “Resilience Project” are now looking for such individuals who they call “unexpected heroes”: Adults who are “resilient to a certain rare disease despite carrying genetic mutations that would indicate onset of the disease in childhood.” In order to find those rare individuals, they are asking for volunteers to donate DNA samples for the project. Since they expect only 1 of 20,000 individuals to be such an “unexpected hero”, they need to analyze the genomes of more than 100,000 individuals. Participants can register online and will receive a test kit by mail. In return, the volunteers get a report indicating whether any of the analyzed mutations have been found in his or her genome.

The researchers hope to identify genes that can “buffer” the effects of the mutations, as well as environmental factors which help people carrying the mutations to stay healthy. The goal is to find new treatments, or even prevent people from getting ill at all.

100,000, 40,000, 25,000, 19,000 – the shrinking human genome…

DNAFor sure many of you remember old textbooks, in which the total number of genes in the human genome was estimated around 40,000 to 100,000. After the human genome was sequenced this number shrunk to 26,000 – 40,000 genes. The 19th GENCODE release further reduced this number to 20,318 protein-coding genes. But not enough a recent study suggested that the actual number of protein-coding genes in humans lies around 19,000.

This astonishing result could be obtained by analyzing the data derived from seven large MS-based proteomics studies from more than 50 human tissues.

But the shrinking number of genes is not the only remarkable results – find below the most important results from this study as described in a recent ScienceDaily blog post:

  • Close to 12 000 human genes could be unambiguously identified
  • Despite high coverage from seven analyses, 40% of the peptides from the human gene set could not be detected; Possible reasons:
    • Thousands of genes annotated in the human genome did not appear in the proteomics analysis.
    • Apparently 1,700 genes that were previously thought to produce proteins most certainly don’t
  • Another hypothesis is that more than 90% of human genes produce proteins originating in metazoans or multicellular organisms living hundreds of millions of years ago
  • The difference between humans and primates at the gene and protein level is very small
  • “The number of new genes that separate humans from mice may even be fewer than 10”
  • Physiological and developmental differences between primates are more likely caused by gene regulation than by differences in the basic functions of proteins in question

Alfonso Valencia, the main researcher behind this project states that “the human genome is best annotated, but we still believe that 1,700 genes may have to be re-annotated”.

According to Alfonso Valencia these results may redefine the entire mapping of the human genome.

Genomics – A Curse Or A Blessing?

Is sequencing your personal genome a curse or a blessing? A recent radio broadcast from NPR news summarises two scientist’s opinions and their practical experiences with genome sequencing  (listen to the radio broadcast below).

World renowned scientist James Watson, from the famous Watson & Crick team that discovered the DNA structure, recently sequenced his own genome. His discovery didn’t earn him the next Nobel prize for science, but he found out that he belongs to the elite few people whose body is more sensitive to ß-blockers. Now James Watson finally realized why it was so difficult for him to balance his blood pressure. It definitely paid off for Watson to sequence his own genome since he could significantly reduce his weekly ß -blocker intake. But despite this “health-changing” experience, he forbid his colleagues to reveal any information about his likelihood to develop Alzheimer. He said, “since you cannot cure it why would you like to know about it?”

The second candidate to share his experience after he personally sequenced his genome is Stanford geneticist Michale Snyder. His genome sequencing revealed that he was at high risk to develop Type 2 diabetes. A few months after his discovery, Synder got the disease that his genome anticipated. Was this a coincidence or fate? For Snyder, knowledge about his genome gave him a head start against the disease.  By completely transforming his diet and participating in various sport activities,  he overcame his Type 2 diabetes.

From my perspective, both examples show that knowledge about our genetic information can be useful in preventing and treating diseases. It boils down to how much experience exist to reliably interpret the data.

The first human genome exhibit at The Smithsonian Institution

Last week The Smithsonian Institution’s National Museum of Natural History at Washington DC announced a new exhibit to celebrate the 10th anniversary of the completion of the human genome. The project is a collaboration between the museum and the National Human Genome Research Institute, with major funding coming from the Life Technologies Foundation. It will open in 2013 to the 7 million annual visitors of the museum.


“The goal of the exhibition is not just to celebrate but to look ahead and acknowledge that we are in the early stages of a very exciting genomic era, that we have learned a remarkable amount about how the genome works and how it contributes to health and disease, and that the pace of research is only accelerating and becoming increasingly relevant to people,” said NHGRI Director Eric Green.
Also announced last week was a new grant program by the NHGRI to study newborn genome sequencing. It will provide $25 million to study how whole genome or whole exome sequencing will benefit newborn care as well as its social implications.
“Genome”, “genomics” etc used to be terms understood by few outside of biology and bioinformatics. This is changing rapidly. It is exciting time ahead of us to witness the genomics revolution.