Journal List > Korean J Perinatol > v.25(3) > 1013709

Cho: Next Generation DNA Sequencing and Its Application in Clinical Medicine

Abstract

Watson and Crick published a paper on the double helical structure of DNA in Nature in April 25, 1953. The human genome is contained in the 23 pairs of chromosomes and in the mitochondrial DNA of each cell. The Human Genome Project was launched in 1990 under the direction of Watson and concluded in 2003, on the 50th anniversary of Watson and Crick paper. Over 6 billion of nucleotides of genetic codes are in single cells. There are 23,000 protein coding genes and the remainder are non-coding DNA, regulatory DNA. Since the completion of Human Genome Project, these huge genomic information has been translated into clinically usable medical information. With the advent of massively parallel DNA sequencing, known as next generation DNA sequencing, the cost and turn-around time were significantly reduced so that the era of Whole Genome Sequencing entered into hospitals and medical clinics. On June 16, 2014 American Society of Human Genetics revised its mission statement as follows. “Our mission is to advance human genetics in science, health and society through research, education and advocacy”. Finally medical genetics nestled its roots in the midst of genetics and genomics.

REFERENCES

1.Green RC., Berg JS., Grody WW., Kalia SS., Korf BR., Martin CL, et al. ACMG recommendations for reporting of inci-dental findings in clinical exome and genome sequencing. Genet Med. 2013. 15:565–74.
crossref
2.Grody WW., Thompson BH., Hudgins L. Whole-exome/genome sequencing and genomics. Pediatrics. 2013. 132(Suppl 3):211–5.
crossref
3.Bianchi DW., Parker RW., Wentworth J., Madankumar R., Saffer C., Das AF, et al. DNA sequencing versus prenatal aneuploidy screening. N Eng J Med. 2014. 370:799–808.
4.Bianchi DW., Platt LD., Goldberg JD., Abuhamad AZ., Sehnert AJ., Rava RP. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012. 119:890–901.
crossref
5.Greene MF., Phimister EG. Screening for trisomies in circulating DNA. N Engl J Med. 2014. 370:874–5.
crossref
6.Simpson JL. Is cell-free fetal DNA from maternal blood finally ready for prime time? Obstet Gynecol. 2012. 119:883–5.
crossref
7.Landau YE., Lichter-Konecki U., Levy HL. Genomics in newborn screening. J Pediatr. 2014. 164:14–9.
crossref
8.Greeley SA., Msall ME., Acharya K. Genomic sequencing in newborn screening programs. JAMA. 2012. 307:2146–7.
crossref
9.Shah AA., Wang D., Hirsch E. Next-generation sequencing of maternal serum to detect viruses in women with labor or premature rupture of membranes. Obstet Gynecol. 2014. 123(Suppl 1):35–6.
crossref
10.Korf BR., Rehm HL. New approach to molecular diagnosis. JAMA. 2013. 309:1511–21.
11.Jacob HJ. Next-generation sequencing for clinical diagnostics. N Eng J Med. 2013. 369:1557–8.
crossref
12.Abdul-Karim R., Berkman BE., Wendler D., Rid A., Khan J., Badgett T, et al. Disclosure of incidental findings from next-generation sequencing in pediatric genomic research. Pediatrics. 2013. 131:564–71.
crossref

Table 1.
Disease gene panels that use next-generation sequencing
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Hereditary arrhythmias (channelopathies)
Retinitis pigmentosa
Albinism
Intellectual disability
DNA repair defects
Skeletal dysplasia
Disorders of sexual development
Hearing loss
Table 2.
Conditions, genes, and variants recommended for return of incidental findings in clinical sequencing
Phenotype MIM-disorder PMID-Gene Reviews entry Typical age of onset Gene MIM-gene Inheritancea Variantsa to reportb
Hereditary breast and ovarian cancer 604370 20301425 Adult BRCA1 113705 AD KP and EP
612555 BRCA2 600185
Li-Fraumeni syndrome 151623 20301488 Child/adult TP53 191170 AD KP and EP
Peutz-Jeghers syndrome 175200 20301443 Child/adult STK11 602216 AD KP and EP
Lynch syndrome 120435 20301390 Adult MLH1 120436 AD KP and EP
MSH2 609309
MSH6 600678
PMS2 600259
Familial adenomatous polyposis 175100 20301519 Child/adult APC 611731 AD KP and EP
MYH-associated polyposis; adeno-mas, multiple colorectal, FA type 2; colorectal adenomatous Polyposis, autosomal recessive, with pilomatricomas 608456 23035301 Adult MUTYH 604933 ARC KP and EP
132600
Von Hippel-Lindau syndrome 193300 20301636 Child/adult VHL 608537 AD KP and EP
Multiple endocrine neoplasia type1 131100 20301710 Child/adult MEN1 613733 AD KP and EP
Multiple endocrine neoplasia type2 171400 20301434 Child/adult RET 164761 AD KP
162300
Familial medullary thyroid cancerd 1552401 20301434 Child/adult RET 164761 AD KP
PTENhamartoma tumor syndrome 153480 20301661 Child/adult PTEN 601728 AD KP and EP
Retinoblastoma 180200 20301625 Child RB1 614041 AD KP and EP
Hereditary paraganglioma-pheochromocytoma syndrome 168000 (PGL1) 20301715 Child/adult SDHD 602690 AD KP and EP
601650 (PGL2) SDHAF2 613019
605373 (PGL3) SDHC 602413 KP and EP
115310 (PGL4) SDHB 185470
Tuberous sclerosis complex 191100 20301399 Child TSC1 605284 AD KP and EP
613254 TSC2 191092
WT1-related Wilms tumor 194070 20301471 Child WT1 607102 AD KP and EP
Neurofibromatosis type2 101100 20301380 Child/adult NF2 607379 AD KP and EP
Ehlers-Danlos syndrome, vascular type 130050 20301667 Child/adult COL3A1 120180 AD KP and EP
Marfan syndrome, Loeys-Dietz syndromes, and familial thoracic Aortic aneurysms and dissections 154700 20301510 Child/adult FBN1 134797 AD KP and EP
609192 20301312 TGFBR1 190181
608967 20301299 TGFBR1 190182
610168 SMAD3 603109
ACTA2 102620
MYLK 600922
MYH11 160745

a Some conditions that may demonstrate semidominant inheritance (SD) have been indicated as autosomal dominant (AD) for the sake of simplicity. Others have been labeled as X-linked (XL);

b KP: known pathogenic, sequence variation is previously reported and is a recognized cause of the disorder; EP: expected pathogenic, sequence variation is previously unreported and is of the type that is expected to cause the disorder. Note: The recommendation to not repot expected pathogenic variants for some genes is due to the recognition that truncating variants, the primary type of expected pathogenic variants, are not an established cause of some diseases on the list.

c Although carriers may have modestly increased risk, we recommend searching only for individuals with biallelic mutations;

d On the basis of evidence presented to the Working Group after the online posting of these recommendations, the decision was made to remove one gene, NTRK1, from the recommended list. Abbreviations: MIM, Mendelion Inheritance in Man; PMID, PuMed identifier; MYH, mutY homolog; FAP, familial adenomatous polyposis; WT1, Wilms tumor1

Table 2.
Continued
Phenotype MIM-disorder PMID-Gene Reviewsentry Typical age y of onset Gene MIM-gene Inheritance a Variants to reportb
Hypertrophic cardiomyopathy, dilated cardiomyopathy 115197 20301725 Child/adult MYBPC3 600958 AD KP and EP
192600 MYH7 160760 KP
601494 TNNT2 191045 KP and EP
613690 TNNI3 191044 KP
115196 TPM1 191010
608751 MYL3 160790
612098 ACTC1 102540
600858 PRKAG2 602743
301500 GLA 300644 XL KP and EP (hemi, het, hom)
608758
115200
MYL2 160781 AD KP
LMNA 150330 KP and EP
Catecholaminergic polymorphic ventricular tachycardia 604772 RYR2 180902 AD KP
Arrhythmogenic right-ventricular cardiomyopathy 609040 20301310 Child/adult PKP2 602861 AD KP and EP
604400 DSP 125647
610476 DSC2 125645
607450 TMEM43 612048 KP
610193 DSG2 125671 KP and EP
Romano-Ward long QT syndrome Types 1, 2, and 3, Brugada syndrome 192500 20301308 Child/adult KCNQ1 607542 AD KP and EP
613688 KCNH2 152427
603830 SCN5A 600163
601144
Familial hypercholesterolemia 143890 No Child/adult LDLR 606945 SD KP and EP
603776 Gene reviews APOB 107730 SD KP
Entry PCSK9 607786 AD
Malignant hyperthermia susceptibility 145600 20301325 Child/adult RYR1 180901 AD KP
CACNA1S 114208

a Some conditions that may demonstrate semidominant inheritance (SD) have been indicated as autosomal dominant (AD) for the sake of simplicity. Others have been labeled as X-linked (XL);

b KP: known pathogenic, sequence variation is previously reported and is a recognized cause of the disorder; EP: expected pathogenic, sequence variation is previously unreported and is of the type that is expected to cause the disorder. Note: The recommendation to not report expected pathogenic variants for some genes is due to the recognition that truncating variants, the primary type of expected pathogenic variants, are not an established cause of some diseases on the list.

c Although carriers may have modestly increased risk, we recommend searching only for individuals with biallelic mutations;

d On the basis of evidence presented to the Working Group after the online posting of these recommendations, the decision was made to remove one gene, NTRK1, from the recommended list.

TOOLS
Similar articles