...; (d) identification of sites of variation across study samples, and (e) determination of accurate sample genotypes at each site of variation. Genomic regions targeted for sequencing can be the entire genome, the entire exome or a set of candidate genes or regions. Whole genome sequencing...

... cost-effective sequencing, has been coupled to effective methods for exome pulldown. This has dramatically increased the pace of discovery of genes underlying mendelian forms of severe insulin resistance. Here, we review progress in the identification of genetic causes of severe disorders of insulin...

... the genetic subtype defines the treatment. Mutations in at least 26 genes have been identified through studies using genetic linkage, candidate gene sequencing and most recently, exome sequencing. With the advent of next-generation sequencing technology, it is now possible to do a single test to identify...

... and analyses, we expect these issues to resolve and genomic information to play a central role in the identification of novel causes of DSD, as well as the diagnosis and management of DSD [ 3 ]. Whole Genome or Exome? Whole genome sequencing (WGS) and whole exome sequencing (WES) have their advantages...

... CJ, Davis SA, Bailey AR: The false-positive in universal newborn hearing screening. Pediatrics 2000;106:E7. 42. de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, et al: Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 2012;367:1921-1929. 43...

... A, Ponting CP: Sequencing depth and coverage: key considerations in genomic analyses. Nat Rev Genet 2014;15:121-132. 5. Asan, Xu Y, Jiang H, Tyler-Smith C, Xue Y, Jiang T, Wang J, Wu M, Liu X, Tian G, Wang J, Wang J, Yang H, Zhang X: Comprehensive comparison of three commercial human whole-exome capture...

..., Wang M, Burgess DL, Kovar C, et al: Whole exome capture in solution with 3 Gbp of data. Genome Biol 2010;11:R62. 31. Turner EH, Lee C, Ng SB, Nickerson DA, et al: Massively parallel exon capture and library-free resequencing across 16 genomes. Nat Methods 2009;6:315-316. 32. Koboldt DC, Larson...

... . Bioinformatics 2012;28:1307-1313. 27. Krumm N, Sudmant PH, Ko A, O'Roak BJ, Malig M, Coe BP, Quinlan AR, Nickerson DA, Eichler EE: Copy number variation detection and genotyping from exome sequence data . Genome Res 2012;22:1525-1532. 28. Fromer M, Moran JL, Chambert K, Banks E, Bergen SE, Ruderfer DM...

... Technologies Genomic analysis technologies such as whole-exome sequencing have been productively applied to the discovery of the etiology of rare single gene disorders and have provided clinical insight into the etiology of complex disorders [ 42 , 43 , 44 , 45 , 46 ]. Innovative genomic analysis...

... in a vast dataset that encompasses whole genomes, coding exomes (approximately 2% of the genome), transcriptomes, DNA methylomes, and targeted proteomes, in addition to clinical data. To distinguish potential driver mutations from passenger mutations, two separate algorithms were used to evaluate samples...

... catalogue of somatic mutations from a human cancer genome. Nature 2010;463:191-196. 11. Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y: Exome sequencing identifies GRIN2A as frequently mutated...

... of a nonsyndromic deafness locus on chromosome 9q34.3. Eur J Hum Genet 2010;18:125-129. 42. Walsh T, Shahin H, Elkan-Miller T, Lee MK, Thornton AM, et al: Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. Am J...

... against the potential for progressive hearing loss. The possibility of hearing loss due to congenital HCMV should be considered before embarking on more expensive genetic investigations such as whole-exome or whole-genome sequencing. Diagnostic Challenges Occult Features of Hearing Loss Syndromes...

... T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J: Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009;461:272-276. 51. Bruneau BG, Srivastava D: Congenital heart disease: entering a new era of human genetics. Circ Res 2014;114:598-599...

..., targeted single-gene and panel sequencing, and NGS of the whole genome or exome. Aneuploidy Cytogenetic analysis is the microscopic visualization of the chromosomes. Abnormalities in chromosomes can involve an extra or a missing chromosome such as trisomy 21 in Down syndrome (see Kruszka chapter...

... gene mutations, codifying for a loss-of-function protein termed parafibromin. Whole exome sequencing identified mutations in other genes, such as mTOR , KMT2D , CDKN2C , THRAP3 , PIK3CA , and EZH2 genes , CCND1 gene amplification. The diagnosis of PC is quite difficult due to the lack...

... Graeve F, Lecoeur C, Sand O, Vaxillaire M, Froguel P: Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PloS One 2012;7:e37423. 42. Rigoli L, Lombardo F, Di Bella C: Wolfram syndrome and WFS1 gene. Clin Genet 2011;79:103-117. 43. Zalloua PA, Azar...

... Abstract High-throughput sequencing of multiple human exomes and genomes is rapidly identifying rare genetic variants that cause or contribute to disease. Microarray-based methodologies have also shed light onto the genes that contribute to common, non-disease human traits such as hair and eye...

... Abstract Since the publication of the first draft of the human genome sequence in 2001, there has been an explosion in the number of genes associated with human genetic diseases, including those involved in human deafness. Clinical studies, genome-wide association studies, and exome...