Applications of long-read sequencing to Mendelian genetics

被引:0
作者
Francesco Kumara Mastrorosa
Danny E. Miller
Evan E. Eichler
机构
[1] University of Washington School of Medicine,Department of Genome Sciences
[2] University of Washington and Seattle Children’s Hospital,Division of Genetic Medicine, Department of Pediatrics
[3] University of Washington,Department of Laboratory Medicine and Pathology
[4] University of Washington,Brotman Baty Institute for Precision Medicine
[5] Howard Hughes Medical Institute,undefined
[6] University of Washington,undefined
来源
Genome Medicine | / 15卷
关键词
Long-read sequencing; Genetic variation; Medical genetics; Structural variation; Mendelian disorders;
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摘要
Advances in clinical genetic testing, including the introduction of exome sequencing, have uncovered the molecular etiology for many rare and previously unsolved genetic disorders, yet more than half of individuals with a suspected genetic disorder remain unsolved after complete clinical evaluation. A precise genetic diagnosis may guide clinical treatment plans, allow families to make informed care decisions, and permit individuals to participate in N-of-1 trials; thus, there is high interest in developing new tools and techniques to increase the solve rate. Long-read sequencing (LRS) is a promising technology for both increasing the solve rate and decreasing the amount of time required to make a precise genetic diagnosis. Here, we summarize current LRS technologies, give examples of how they have been used to evaluate complex genetic variation and identify missing variants, and discuss future clinical applications of LRS. As costs continue to decrease, LRS will find additional utility in the clinical space fundamentally changing how pathological variants are discovered and eventually acting as a single-data source that can be interrogated multiple times for clinical service.
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[1]  
Kingsmore SF(2019)A randomized, controlled trial of the analytic and diagnostic performance of singleton and trio, rapid genome and exome sequencing in ill infants Am J Hum Genet 105 719-33
[2]  
Cakici JA(2020)Genome sequencing as a diagnostic test in children with unexplained medical complexity JAMA Network Open. 3 eabj6965-53
[3]  
Clark MM(2022)Segmental duplications and their variation in a complete human genome Science 376 44-614
[4]  
Gaughran M(2022)The complete sequence of a human genome Science. 376 597-675.e19
[5]  
Feddock M(2020)Long-read human genome sequencing and its applications Nat Rev Genet. 21 1784-51
[6]  
Batalov S(2019)Multi-platform discovery of haplotype-resolved structural variation in human genomes Nat Commun. 10 663-8
[7]  
Costain G(2019)Characterizing the major structural variant alleles of the human genome Cell. 176 444-31
[8]  
Walker S(2020)A structural variation reference for medical and population genetics Nature. 581 eabf7117-6
[9]  
Marano M(2021)Haplotype-resolved diverse human genomes and integrated analysis of structural variation Science 372 302-49
[10]  
Veenma D(2021)Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads Nat Biotechnol. 39 623-53