The Application of Exome Sequencing in Disease Research

Exon is a part of eukaryotic genome sequence. The exome is the total of all exons, which takes one percent in the whole genome sequence of human beings. The exome sequencing is to capture and enrich the exome in the whole genome sequence by targeted capture, and get the genomic information by next generation sequencing.
Because it has a lower cost than whole genome sequencing, and it can know more protein-coding information at the same cost, it is widely used for all kinds of disease research.
Nerve related diseases
It is well-known that the mutations of APP, PSEN1, and PSEN2 will lead to the Alzheimer’s disease. However, in the research of Guerreiro on 95 patients with AD, he found the mutation of NOTCH3 in exome. That means that the NOTCH3 may have relationships with AD. Cheng’s research of autism spectrum disorder found that ANK3may be related to ASDS. Veltman of human genome research institute in Holland found that new mutation was the key factor of mentally handicapped, and the exome sequencing could be the best detection method.
Mendelian disorders
Disease like sickle cell disease is caused by mutation of a single gene. It is also called Mendelian disorders. For a long time researchers identify the pathogenesis by analyzing the genetic model of family. This situation changed with the appearance of exome sequencing. By filtration of unchanged and common mutation, researchers can identify the mutation gene precisely.
Musculoskeletal system
The Charcot-Marie-Tooth disease is also called peroneal myoatrophy. The research of Michael found that one of the causal factors of CMT is the missense mutation of DYNC1H1 by exome sequencing. Rosewich found that ATPIA3 would lead alternating hemiplegia of childhood.
Metabolism-associated diseases
Jacseung analyzed the genome of congenital VB12 metabolic disorders patients by exome and target region sequencing and found the mutation of ABCD4 will lead to congenital VB12 metabolic. This can be also used in the congenital disorder of glycosylation research.
Skin diseases
The oculocutaneous albinism is a kind of autosomal recessive disorder with genetic heterogeneity and single gene inheritance disease. By whole-exome sequencing, researchers found that the OCA6 was the new disease-causing gene of oculocutaneous albinism. The exome sequencing is also used for the research of hidradenitis and keratosis.
Mitochondrial DNA depletion syndrome
Researchers did exome sequencing for the mtDNA of female India’s brain mitochondria myopathy patients and found the homozygous missense mutation of SUCLA2. This will lead to great amount of deficiencies of the mitochondrial respiratory chain, and finally lead to Mitochondrial DNA depletion syndrome.