Techniques, test interpretation, variant classification, and nomenclature.
Chapters
Biochemical diagnostic testing measures analytes (metabolites, enzymes, transport proteins) to identify inborn errors of metabolism (IEM). Biochemical
Identity testing uses highly polymorphic short tandem repeat (STR) markers to compare DNA profiles between samples. The clinical genetics laboratory a
Newborn screening (NBS) is a public health program that tests all newborns for a panel of serious, treatable conditions in the first days of life. Usi
Predictive testing is genetic testing of an asymptomatic individual to estimate future risk of disease or differential drug response. It is distinct f
Invasive prenatal testing, chorionic villus sampling (CVS) and amniocentesis, obtains fetal cells for direct diagnostic genetic analysis. Unlike scree
Prenatal genetic testing encompasses screening and diagnostic approaches used to assess the risk of or diagnose genetic conditions in a developing fet
Noninvasive prenatal screening (NIPS), also called cellfree DNA (cfDNA) screening, analyzes fragments of placental DNA circulating in the maternal blo
Carrier screening identifies individuals who are heterozygous for pathogenic variants in autosomal recessive or Xlinked conditions. Its purpose is to
Preimplantation genetic testing (PGT) is the analysis of embryos generated through in vitro fertilization (IVF) before transfer to the uterus. It allo
A karyotype is a visual representation of an individual's chromosomes arranged by size, centromere position, and banding pattern. Gbanding (Giemsa ban
Chromosomal microarray analysis (CMA) is a highresolution genomewide assay that detects copy number variants (CNVs), deletions and duplications, acros
Fluorescence in situ hybridization (FISH) uses fluorescently labeled DNA probes that hybridize to complementary sequences on chromosomes, allowing vis
Quality assurance (QA) and quality control (QC) together ensure that a clinical laboratory produces accurate, reproducible, and clinically actionable
US clinical genetic laboratories operate under a layered regulatory structure. CLIA sets the federal floor for any lab testing human specimens for dia
Laboratory safety in a clinical genetics lab encompasses biological, chemical, physical, and wastestream hazards. The dominant frameworks are CDC/NIH
The analytical phase covers nucleic acid extraction, the assay itself, and the perrun quality control that determines whether a run is valid. The over
The preanalytical phase covers everything that happens before the specimen reaches the bench: test ordering, patient identification, collection, label
Polymerase chain reaction (PCR) is a method for exponentially amplifying a specific DNA sequence in vitro. It is foundational to nearly all molecular
Multiplex ligationdependent probe amplification (MLPA) is a PCRbased method that detects copy number changes (deletions and duplications) at up to ~50
Nextgeneration sequencing (NGS), also called massively parallel sequencing, enables simultaneous sequencing of millions of DNA fragments. NGS has tran
Sanger sequencing (dideoxy chain termination method) is a firstgeneration DNA sequencing technique developed by Frederick Sanger in 1977. It remains t
The International System for Human Cytogenomic Nomenclature (ISCN) provides standardized rules for describing chromosomal findings from karyotyping, F
The Human Genome Variation Society (HGVS) nomenclature is the standard system for describing sequence variants at the DNA, RNA, and protein levels. It
The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published standardized guidelines in 20
Genomic databases are essential tools for variant interpretation, providing curated information on variant pathogenicity, population frequency, genedi
Clonal hematopoiesis is the agerelated expansion of a single hematopoietic stem cell clone carrying a somatic variant, in a person with no cytopenia a
Sequence variants are smallscale alterations of the DNA sequence detectable by shortread nextgeneration sequencing (NGS) and Sanger confirmation. They
Tumor genomic testing addresses questions distinct from germline interpretation: what drives this cancer, what therapy will work, is the patient in re
Structural variants (SVs) are genomic alterations larger than ~50 bp, including copynumber variants, balanced and unbalanced rearrangements, and inver
