As we all know, proteins play important roles in human bodies since all physiologic events are related to the structural or mechanical functions of certain proteins. Studying the synthesis process of proteins is a way to study the etiology, pathophysiology, diagnosis, and treatment of certain diseases. The human genome contains approximately 3 billion base pairs of DNA. Among them, only about 30 million base pairs of DNA carry the information for protein synthesis. This part of the genome is called the exome. Exome is valuable in researchers' eyes as it is the origin of protein synthesis. With the development of exome-enrichment strategies and high-throughput sequencing, whole exome sequencing (WES) becomes possible. WES is a more cost-effective method compared to whole genome sequencing and has been applied in evolutionary and medical research and clinical practice.
Application in evolution research
The genome is an encyclopedia, telling us the stories that happened throughout the history of human beings. Whole exome sequencing could be helpful in solving the puzzle of human evolution. By studying anthropology, intervention in some diseases could be more efficient. Take esophageal carcinoma as an example. In China, people from two areas have a high incidence of esophageal carcinoma: Tai Mountain and the Chaoshan area in Guangdong Province. The languages, customs, lifestyles, foods, and climates are quite different from each other. Historical study suggests that they may share the same ancients. Whole exome sequencing has been applied so as to figure out a gene expression map of people from these two areas.
Application in medical research
Etiology research. There are lots of untreated diseases with unknown etiologies, which are called idiopathic diseases in clinics. Without knowing the causes, these diseases could only be diagnosed and treated according to symptoms, such as primary hypertension and primary amenorrhea. All we know is that these diseases are not secondary. Doctors used to study these diseases by monitoring patients' vital signs and analyzing laboratory test results. Then, with the development of biological technology, the physiological alternation is found at tissue, cellular, or even molecular levels. Lots of idiopathic diseases are proven to be related to the dysfunction or deficiency of certain proteins. For further analysis of the etiology of idiopathic diseases, whole exome sequencing allows us to figure out the origin of protein dysfunction or deficiency.
One example is lysosomal storage disease. This group of diseases is defined as lysosomal dysfunction, which results in delayed growth, deafness, or dementia. Lysosomes are a type of organelle that breaks down certain substances inside cells. We know little about the mechanisms of lysosomal storage diseases. Nowadays, researchers have found several genes related to this group of diseases by using whole exome sequencing. By knowing the functioning genes, exploration like gene knock-out experiments can be performed to further understand the mechanism of this group of diseases. Another example is cancer with an unknown etiology. By analyzing the etiology of cancer, doctors could figure out prevention strategies. Figure 1 shows a typical etiology study using whole exome sequencing.
Epidemiology research. The risks of getting certain diseases vary among individuals. Some of the diseases are easily developed in certain groups of people. The variety of incidence is due to the differences in sanitary conditions, culture, and genetic factors. It is easy to compare the sanitary condition and culture through social studies. But it is difficult to study the genetic factors because the quantity of the genome is so large. Current psychiatrists benefit a lot from whole exome sequencing, as it solves the problem above.
Take Alzheimer's disease as an example. Alzheimer's disease is a chronic degenerative disease resulting in dementia. Symptoms like memory loss usually happen to old people. When they get older, the symptoms become more severe. It is irreversible progress. What we can do is early intervention. However, people could hardly distinguish whether their grandfather had a behavior change or was just in a bad mood, unless they were trained. This prevents early intervention. There is a project called the Alzheimer's Disease Sequencing Project, which would perform whole exome sequencing on more than 5,000 patients so as to draw out the genes responsible for Alzheimer's diseases. This will be a strong supporting material in epidemiologic practice, as the local government could come up with a prevention project more specifically according to the gene-expressing condition of the residents.
