Table 1:

Genetic Testing platforms available for clinical testing

Genetic testing platform		Genomic regions interrogated	Type of genetic variations that can be detected	When to consider using for disorders of low bone mass and increased bone fragility
DNA Sequencing	Sanger sequencing	Exonic regions and exon-intron boundaries of single or few genes	SNV, indels	Suspicion of clinical diagnosis of a particular disorder is strong and only one to few genes need to be sequenced (e.g., ALPL sequencing in HPP)
	Gene panel testing using MPS	Exonic regions and exon-intron boundaries of few to hundreds of genes known to cause particular type of human diseases	SNV, indels, CNV of genes included in the panel	Clinical findings can narrow down the diagnostic category, but genetic heterogeneity necessitates interrogation of multiple genes (e.g., osteogenesis imperfecta gene panel in individuals with severe OI)
	Exome sequencing	Exonic regions and exon-intron boundaries of thousands of genes known to cause human diseases	SNV, indels, CNV of exonic regions of genome	Multisystem disorder; phenotype is not distinct to make a diagnosis or narrow down to a diagnostic category; undiagnosed diseases
	Whole genome sequencing	Whole genome	SNV, indels, CNV and other genomic rearrangements in coding and non-coding regions of genome	Multisystem disorder; phenotype is not sufficient to make a diagnosis or narrow down to a diagnostic category; undiagnosed diseases
	DNA genotyping microarray	Specific variants in few to hundreds of genes	Targeted assessment of specific variations in the genome	Polygenic risk scoring
Cytogenetic testing	Karyotype	Chromosomes	Chromosomal aneuploidy, large chromosomal deletions, duplications, and rearrangements	Hypogonadism and features suggestive of sex chromosome disorders (e.g., Turner syndrome and Klinefelter syndrome)
	Chromosomal Microarray	Genomic regions that harbor genes known to be associated with human diseases	Chromosomal aneuploidy, and CNV including small chromosomal deletions, duplications, and complex genomic rearrangements	Multisystem disorder, undiagnosed diseases

CNV - copy-number variation; HPP – hypophosphatasia; MPS - massively parallel sequencing; OI osteogenesis imperfecta