Massively parallel DNA-sequencing systems provide sequence of huge numbers of different DNA strands at once. These technologies are revolutionizing our understanding in medical genetics, accelerating health-improvement projects, and ushering to a fully understood personalized medicine in near future. Whole-exome sequencing (WES) is application of the next-generation technology to determine the variations of all coding regions, or exons, of known genes. WES provides coverage of more than 95% of the exons, which contains 85% of disease-causing mutations in Mendelian disorders and many disease-predisposing SNPs throughout the genome. The role of more than 150 genes has been distinguished by means of WES, and this statistics is quickly growing. In this review, the impacts of WES in medical genetics as well as its consequences leading to improve health care are summarized.

Traditional approaches for gene mapping from candidate gene studies to positional cloning strategies have been applied for Mendelian disorders. Since 2005, next-generation sequencing (NGS) technologies are improving as rapid, high-throughput and cost-effective approaches to fulfill medical sciences and research demands. Using NGS, the underlying causative genes are directly distinguished via a systematic filtering, in which the identified gene variants are checked for novelty and functionality. During the past 2 years, the role of more than 100 genes has been distinguished in rare Mendelian disorders by means of whole-exome sequencing (WES). Combination of WES with traditional approaches, consistent with linkage analysis, has had the greatest impact on those disorders following autosomal mode of inheritance; in more than 60 identified genes, the causal variants have been transmitted at homozygous or compound heterozygous state. Recent literatures focusing on identified new causal genes in Mendelian disorders using WES are reviewed in the present survey.

A breakthrough in next generation sequencing (NGS) in the last decade provided an unprecedented opportunity to investigate genetic variations in humans and their roles in health and disease. NGS offers regional genomic sequencing such as whole exome sequencing of coding regions of all genes, as well as whole genome sequencing. RNA-seq offers sequencing of the entire transcriptome and ChIP-seq allows for sequencing the epigenetic architecture of the genome. Identifying genetic variations in individuals can be used to predict disease risk, with the potential to halt or retard disease progression. NGS can also be used to predict the response to or adverse effects of drugs or to calculate appropriate drug dosage. Such a personalized medicine also provides the possibility to treat diseases based on the genetic makeup of the patient. Here, we review the basics of NGS technologies and their application in human diseases to foster human healthcare and personalized medicine.

GJB2 mutations are major causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. However, a few mutations have an ethnic-specific background. We performed a review by means of a meta-analysis to evaluate the influence of the 35delG on ARNSHL. A PubMed, InterScience, British Library Direct, and Sciencedirect search using keywords '35delG', 'GJB2' and 'Connexin 26' associated with 'carrier frequency' was carried out to include all papers from February 1998 to February 2008. 35delG carrier frequencies in 23187 random controls were analysed and categorized, corresponding with geographical boundaries, from all over the world. Mean carrier frequencies of 35delG mutation were found to be 1.89, 1.52, 0.64, 1, and 0.64 for European, American, Asian, Ocean, and African populations, respectively. We found that the average 35delG carrier frequency is highest in southern Europe and lowest in eastern Asia. The south-to-north European gradient in the carrier frequency of 35delG was confirmed and also a west-to-east Asian gradient is suggested. This study highlights the importance of establishing prevalence, based on the local population for screening and diagnostic programs of live births.