NGS-Based Clinical Diagnosis of Genetically Heterogeneous Disorders

  • C. A. Valencia
  • T. A. Sivakumaran
  • B. T. Tinkle
  • A. Husami
  • K. Zhang
Chapter

Abstract

Next-generation sequencing (NGS) has transformed genomic research by decreasing the cost of sequencing and increasing the throughput. NGS platforms have evolved to provide an accurate and comprehensive means for the detection of molecular mutations, and the recent focus is on using NGS technology in clinical diagnosis. NGS analysis has three major components: enrichment, sequencing, and analysis. In the last several years, enrichment technologies based on hybridization or amplification principles have emerged. Similarly, sequencing platforms have continued to improve by increasing the sequencing output and decreasing the sequencing time and cost. Various enrichment and sequencing platform combinations have been utilized for the diagnosis of genetically heterogeneous disorders, and it is the topic of discussion for this chapter. We describe the employment of NGS approaches to the diagnosis of genetically heterogeneous disorders and mention advantages and challenges of these technologies in a clinical laboratory setting.

Keywords

Obesity Retina Cardiomyopathy Integrin Arena 

Abbreviations

AF

Atrial fibrillation

APEX

Arrayed primer extension

ARPKD

Autosomal recessive polycystic kidney disease

ARVC

Arrhythmogenic right ventricular cardiomyopathy

BBS

Bardet–Biedl syndrome

CHD

Congenital heart disease

CHF

Congenital hepatic fibrosis

CMD

Congenital muscular dystrophy

CNS

Central nervous system

CSD

Conduction system disease

DCM

Dilated cardiomyopathy

ERG

Electroretinogram

HCM

Hypertrophic cardiomyopathy

HLH

Hemophagocytic lymphohistiocytosis

JBTS

Joubert syndrome-related disorders

LCA

Leber congenital amaurosis

LGMD1B

Limb-girdle muscular dystrophy type 1B

LVNC

Left ventricular noncompaction

MDC1A

Merosin-deficient congenital muscular dystrophy

MDC1C

Congenital muscular dystrophy type 1C

MEB

Muscle-eye-brain disease

MKS

Meckel–Gruber syndrome

NGS

Next-generation sequencing

NPHP

Nephronophthisis

NPHP-AC

Nephronophthisis-associated ciliopathies

PCD

Primary ciliary dyskinesia

PIDD

Primary immunodeficiency disorders

RP

Retinitis pigmentosa

RSS

Rigid spine syndrome

SCD

Sudden cardiac death

SVT

Supraventricular tachycardia

VT

Ventricular tachycardia

WGA

Whole genome amplification

WWS

Walker–Warburg syndrome

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • C. A. Valencia
    • 1
    • 2
  • T. A. Sivakumaran
    • 1
    • 2
  • B. T. Tinkle
    • 1
    • 2
  • A. Husami
    • 1
    • 2
  • K. Zhang
    • 1
    • 2
  1. 1.Division of Human GeneticsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of PediatricsUniversity of Cincinnati Medical SchoolCincinnatiUSA

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