Genomics in general practice

Summary of genetic tests

Tests and indications

The following table provides information about genetic tests that may be encountered in general practice and the tests’ indications. 

Genetic Test Indications
G-banded (conventional microscopic) karyotype – Chromosomes are stained to reveal patterns of alternating light and dark bands Suspected chromosome rearrangement; investigate multiple miscarriages
Fluorescence in situ hybridisation (FISH) – Using fluorescent tags specific to a chromosomal region, FISH can visualise chromosomes to identify abnormalities Determine physical arrangement of chromosomal conditions or correct number of chromosomes (eg rapid method of aneuploidy screening in prenatal setting)
Chromosomal microarray (CMA) or molecular karyotype (eg single nucleotide polymorphism [SNP] microarray) – CMA uses a microchip-based platform to perform a genome-wide assay that looks for sub-microscopic copy number variants (CNVs). These variants are extra (duplications) or missing (deletions) segments of deoxyribonucleic acid (DNA). Many CNVs are common and benign (and therefore not reported by the laboratory), some are pathogenic and others are of uncertain significance Unexplained intellectual disability or developmental delay; dysmorphic facial features; prenatal investigation of abnormality on ultrasound
Sanger sequencing – The exact order of base pairs A, G, T and C in an individual‘s genetic makeup is known as the DNA sequence. Sanger sequencing is old, low through-put, but reliable technology, and sequences just one gene at a time Suspect condition with a known single-gene cause (eg cystic fibrosis, thalassaemia)
Next generation sequencing (NGS) or massively parallel sequencing – NGS sequences millions of small DNA fragments, which are then mapped to a reference genome. NGS can sequence the entire genome, just the exome (coding genes) or a panel of selected genes Genome sequencing: A comprehensive approach that captures the entire genome (~3 billion nucleotides)
Exome sequencing: A more cost-effective approach to capture and analyse all known disease-causing genes (eg rare childhood syndromes) (~30 million nucleotides)
Panel sequencing: A more targeted approach focusing on key genes related to a clinical indication (eg cancer, cardiac conditions)
SNP genotyping or genomic profiling or scan – Testing that analyses single nucleotide variations in the genome Determine ability to metabolise certain drugs (eg CYP2D6, codeine), paternity testing, personal genomic testing (direct to consumer)
Polygenic risk score A polygenic risk score uses information about disease risk associated with multiple common variants, or SNPs, to estimate the risk for an individual of developing that disease. Indications. Personal genomic testing. Potential applications in cancer screening and chronic disease prevention. Currently polygenic risk scores may only be useful for people of European ancestry as there are not enough data available yet to reliably apply them to non-European populations.
Polymerase chain reaction (PCR) – A method for amplifying DNA (ie making millions of copies of a particular sequence of DNA) Disorders caused by triplet repeat expansions (eg fragile X syndrome, Huntington’s disease)
Multiplex ligation-dependent probe amplification (MLPA) – A PCR method of detecting copy number variants Disorder caused by large deletions or duplications of specific genes (eg Duchenne muscular dystrophy)
DNA methylation studies of specific chromosome region Disorders caused by abnormal gene methylation which affects gene expression (eg Prader Willi syndrome, Beckwith–Wiedemann syndrome)
Maternal serum screening
Combined first trimester screening – Biochemical screening of maternal blood combined with ultrasound
Second trimester serum screening – Biochemical screening of maternal blood
First trimester: Screening at 11–13 weeks to estimate risk for trisomy 21, trisomy 18, trisomy 13
Second trimester: screening at 14–20 weeks to estimate risk for trisomy 21, trisomy 18 and neural tube defects
Non-invasive prenatal testing (NIPT) – Analysis of cell-free fetal DNA (cfDNA) in maternal plasma Pregnancy screening from 10 weeks to detect evidence of fetal aneuploidy with higher sensitivity and specificity than maternal serum screening

Adapted from Donoghue S, Downie L, Stutterd C. Advances in genomic testing. Aust Fam Physician 2017;46(4):200–05. Available at [Accessed 27 July 2017].