The sequencing of the human genome has triggered a seismic shift in genetics research. The Human Genome Project so increased the speed with which researchers can generate data that the bottleneck no longer lies in data generation but in data analysis. One area in particular that may benefit from the advances arising from the Human Genome Project is the study of common diseases such as cancer, diabetes, and stroke. Such disorders are caused by complex interactions among genes and environmental factors; the challenge facing researchers now is to find out which genes are involved and how they influence disease. It is hoped that in the long run a better understanding of the genes and their mechanisms will lead to better diagnosis and therapeutic tools.

The Human Genome Project was still under way when Eleftheria Zeggini, Mette Nyegaard, and Anneke den Hollander--young scientists from Greece, Denmark, and the Netherlands, respectively--opted for a career in genetics. Each of them found inspiration in the Human Genome Project and the research frontiers it seemed to open. Via different routes, all were able to find research niches in the post-genome area.

Meet the researchers

Zeggini, now a statistical geneticist, left her native Greece to start her training at UMIST in Manchester, U.K., as a biochemist. She was introduced to genetics research during two paid summer placements--one on genetic variants in oestrogen receptors, the other on the role of a gene called FasL in the rejection of corneal grafts--and those experiences affirmed her interest in the discipline. When she finished her bachelor's degree, Zeggini went to the Arthritis Research Campaign Epidemiology Unit at the University of Manchester to do a Ph.D. on the sequencing of genes related to juvenile oligoarthritis, a complex autoimmune disease.

Zeggini then did a 1-year postdoc at Manchester's Centre for Integrated Genomic Medical Research, where she honed her skills in statistics and started developing computer-based strategies to analyse data from complex, multigene studies. Zeggini stayed in the same field for a second postdoc at the Wellcome Trust Centre for Human Genetics in Oxford, where she now works as a junior group leader in statistical genetics, focussing primarily on type 2 diabetes. She was awarded a Wellcome Trust Research Career Development Fellowship earlier this month to continue her work on the analysis of genetic data and start building her own group.

Mette Nyegaard

Now a postdoc in population genetics, Nyegaard studied biotechnology and chemistry for her undergraduate degree at the University of Aarhus in Denmark. A course in population genetics initially caught her interest. "I was fascinated by how genes are maintained and lost in populations," she says--so she did her final-year undergraduate research project on the genetic causes of depression in Faroe Islanders. She then spent 1 year as a research assistant in the same lab. She did her Ph.D. at the University of Southern Denmark.

Then Nyegaard, together with her husband, also a research scientist, and two children, moved to California for 2 years. She looked after her children during the first year and took a postdoc on mouse models of human fertility in a genetics group at the Stanford School of Medicine in their second year in California. Nyegaard--who also took maternity leaves before and during her Ph.D.--admits that keeping her career on track after three breaks was difficult. "Looking back now, I was worried," she says. But today she is where she wants to be.

She returned with her family to Denmark at the end of 2005, starting another postdoc at the Institute for Human Genetics back at the University of Aarhus. With this move, she also came back to her original interest in population genetics. She now studies the mutations underlying congenital conditions such as hearing loss and manic-depressive illness. Like Zeggini, she is interested in multigene effects, looking at interactions between genes and environmental factors.

Anneke den Hollander

Geneticist den Hollander began her career studying biomedical sciences at the University of Leiden in the Netherlands. Like Zeggini and Nyegaard, this is when she became interested in human genetics. She got hooked during a rotation in a human genetics lab. While she was there, the team discovered a gene that played an important role in Rubinstein-Taybi syndrome, a genetic disease that can cause skeletal abnormalities and mental retardation in patients. She realised then that she "wanted to do research with a clinical relevance."

Her next move was a Ph.D. in the Human Genetics Department at Radboud University in Nijmegen on the genetic causes of congenital blindness. She still works there, now as a postdoctoral scientist pursuing the same lines of research. She uses genome-wide approaches to look for genes that cause congenital blindness.

Academic credentials

An undergraduate degree in genetics is an obvious starting point for a career in health-related human genetics, but the variety of skills needed by researchers in genetics means that students with broader backgrounds can enter the field later. "I think there are many ways into this field," says Nyegaard--but a good grounding in genetics, bioinformatics, statistics, and biochemistry are helpful, she adds. Depending on your area of study, knowledge of anatomy can be useful, too. But genetics is not open only to biologists and medical scientists; even mathematicians can get involved in genetics on the analytical side, Zeggini says. Zeggini picked up statistics along the way; similarly, trained mathematicians--there are many in this field--can learn about genetics on the job, she says.

The right lab experience

Trying their hand at genetics research at an early stage was an important step in the careers of all three researchers. "I think lab work is the best way to get to know a field," says den Hollander, who adds that it's also important to do your homework. "Talk to people. Find out where the best departments are and what they are doing," she advises. "The group is the most important thing," Zeggini adds, advising budding health geneticists to surround themselves with top scientists whose experience they can draw upon.

And even though Zeggini no longer works at the bench, she says that the experience she gained during her lab placements and her Ph.D. was vital for her current work. Even if you are not collecting data, she says, you need to understand how experiments work and to appreciate what it means when something goes wrong.

Job experiences and rewards

Zeggini works with European and international consortia that study the genetic causes of type 2 diabetes. They collect patient data, sequence genes, and look for common mutations in patients. Zeggini's role is to analyse and interpret the data, developing statistical models to get the most out of the data. The goal is to categorise the genes underlying the condition, as well as their interactions with other genes and the environment. Zeggini believes that collaborations will become increasingly important in her field as researchers use ever-larger sample sizes and generate ever-larger volumes of genetic data.

With her current job at the University of Aarhus, Nyegaard has returned to population genetics. She studies how genetic factors correlate with disease in populations, as well as looking for links between genes and disease predisposition in families. One technique she uses is to look at the inheritance pattern of diseases in families and to correlate this pattern with markers on the genome. This way, she says, you can zone in on sections of the genome that contain one or several genes that might play a role in a disease. What Nyegaard enjoys most in her research are the variety and novelty. "I like knowing that what you do has never been done before. That is very rewarding."

Den Hollander seeks new genes associated with diseases. Currently, she is working on single-nucleotide polymorphisms (SNPs)--one-letter changes in a gene's DNA. One of the techniques she uses is SNP microarrays, which enable researchers to screen a genetic sample for many SNPs at once on specially designed DNA 'chips'. A few months ago, her group found a gene that plays an important role in 20% of the cases of congenital blindness. "This is really what you do it for," she says. She finds the clinical applications of her work especially rewarding. Collaborations with ophthalmologists are vital because they "look at the clinical implications of what we find, collect samples, and give us information about phenotype."

Apart from the basic science and clinical skills, the three researchers agree that strong organisational skills are required--and that theirs are pushed to the limit. "It's important that you are very dedicated, precise, and organised, especially when working with large-scale techniques," says den Hollander.

From what these three researchers have seen, the field of human genetics is growing and there is still a need--even an increasing need--for qualified people. "Studies are becoming more and more complicated," says Zeggini--but analysis technology is lagging. The result, she thinks, is a range of new career opportunities. When den Hollander started her Ph.D. in 1996, she says, 80 people in her department were working on DNA diagnostics, genetics, and genomics research. Today, there are about 230, and the department is still growing. Despite the growth, they say, finding funding and a permanent position is challenging.

All three believe that a rewarding career awaits those who can stand up to the field's fast pace and considerable demands. Even though many leaps forward have been made in the field in recent years, many others are likely to follow. "I'm really looking forward to seeing what happens in the next few years," Nyegaard says.

Tune in to the Science podcast to hear one of our interviewees--Eleftheria Zeggini.

Laura Blackburn is a science writer based in Cambridge, U.K.

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