Genetic analysis of hereditary hematological disorders: overview

Abstract

During the past 30 years, our knowledge of congenital/hereditary hematological disorders has dramatically improved due to the identification of their causative genes, which has also provided novel insights into disease pathobiology. More recently, the development of next-generation sequencing (NGS) technologies has provided an unprecedented opportunity to elucidate the genetic basis of rare congenital/hereditary disorders by enabling single nucleotide resolution analysis of patients' genomes. Currently, targeted sequencing, especially whole-exome sequencing (WES), is widely used for analysis of Mendelian disorders. Protein-coding exons constitute about 1.3% of the human genome and are predicted to harbor most of the disease-causing mutations. Therefore, much higher sequence coverage of exonic regions can be achieved more effectively with considerably less sequence data as compared with whole-genome sequencing. In addition to the discovery of novel causative genes, NGS have been used for diagnostic purposes in congenital hematological disorders. WES or targeted sequencing of known causative genes could identify the mutations causing diseases more accurately and effectively than traditional Sanger sequencing. Therefore, the widespread use of NGS for clinical diagnosis (clinical sequencing) of congenital/hereditary hematological disorders, namely, clinical sequencing is anticipated in the near future.