Common Tests
- Karyotype
- Microarray
- Fragile X by PCR with Methylation Studies
- Methylation Studies
- Nucleotide Repeat Expansion
- Single/Multiple Gene Analysis
- Whole Exome Sequencing
- Whole Genome Sequencing (WGS)
- Sponsored Testing
- Analyzes the size, shape, and number of chromosomes to detect extra or missing chromosomes (aneuploidy), chromosome pieces (deletions or duplications) or structural rearrangements (inversions, translocation, etc.).
- Resolution is ≥ 5 Mb.
- A method for detection of genomic imbalances* of chromosomal regions ≥ 50–100kb (*duplication/deletion, gain/loss, Copy Number Variant (CNV)
- First-tier genetic test for developmental disability, intellectual disability, autism spectrum disorder and Multiple Congenital Anomalies not specific to well-delineated syndrome
Related Technologies
- Comparative Genomic Hybridization Microarray (CGH Microarray or aCGH)
- Single Nucleotide Polymorphism microarrays (SNP arrays). SNP arrays can detect Uni Parental Disomy (UPD) and unanticipated findings such as consanguinity and non-paternity
What You Need to Know Before Ordering Chromosomal Microarray
Guidance from the Jackson Laboratory about how, when, and why to order and use chromosomal microarray testing is geared towards developmental pediatricians, but may also be of interest to other health care providers.
The Chromosome Microarray
Dr. Scott McLean, a clinical geneticist at the Children’s Hospital of San Antonio, provided this overview of Chromosome Microarray Testing on November 27th, 2018. This webinar was hosted by the Mountain States Regional Genetics Network.
- Determines trinucleotide repeat (CGG) length and methylation status of the FMR1 promotor
- First-tier test for individuals with developmental disability, intellectual disability, autism spectrum disorder.
- Used to diagnose/rule out FMR1 – Related Disorders (nucleotide repeat expansion disorders) including:
-
- Fragile X syndrome (FXS) – Most common cause of inherited ID and monogenic ASD in males
- Fragile X-associated Tremor/Ataxia Syndrome (FXTAS)
- Fragile X-associated Primary Ovarian Insufficiency (FXPOI)
- Assesses DNA methylation within a particular regulatory region or gene.
- In general, the level of methylation is low to intermediate at regulatory elements Increased methylation on promoters or enhancers can repress transcription.
- Numerous neurodevelopmental disorders are caused by altered, site-specific methylation including: Fragile X, Prader Willi, Angelman, Beckwith Weidemann and Russell Silver.
- Determines the number of nucleotide repeats. For some conditions, the methylation status of the elongated region is also determined.
- Sequence repeats (aka tandem repeats) are normally occurring sequences of repeated nucleotides that are scattered throughout the human genome. The repeats are unstable and can change is size in successive generations.
- More than 40 diseases, most of which primarily affect the nervous system, are caused by expansion (or elongation) of sequence repeats (e.g., Fragile X, Huntington Disease, Myotonic Dystrophy).
- Analysis performed on a single gene or multiple genes simultaneously (Panel).
- Detects Single Nucleotide Variants (SNVs) and CNVs in exons and approx.. 10 bp of flanking intronic regions.
- Chromosomal rearrangements and nucleotide repeat expansions are not analyzed.
- Panels vary in size (2 genes to 1000s of genes) and clinical sensitivity.
- Genes on a panel are either associated with a condition (Ectodermal Dysplasia), broad group of conditions (neuromuscular disorders) or a specific phenotypic feature (e.g., epilepsy, ataxia, macrocephaly & overgrowth).
- Test labs change the gene content of their panels based on new evidence.
- Ordering of a specific panel is guided by clinical findings and judgement (and sometimes insurance coverage). Single gene analysis may be indicated when there is a narrow differential. A panel may be indicated when there is a complex disease presentation or overlapping clinical symptoms.
- Analysis of nearly all exons in nearly all genes.
- Single Nucleotide Variants (SNVs) and CNVs ≥ 4 exons are detected in exons and approx. 10 bp of flanking intronic regions.
- Regulatory domains, deep intronic regions, chromosomal rearrangements, nucleotide repeat expansions and the mitochondrial genome are not analyzed
- Primary, Secondary* and Incidental* Findings are possible. *Opt-in/Opt-out options exist and vary by lab.
- The likelihood of receiving uncertain or ambiguous results increases as the amount of genetic material analyzed increases.
- Pre-test counseling and informed consent is highly recommended.
Position Statements on Exome Sequencing
- Not widely available in a clinical setting.
- Analysis of nearly all exons and introns in nearly all genes, including regulatory domains, deep intronic regions, and the mitochondrial genome.
- Single Nucleotide Variants (SNVs) and CNVs ≥ 4 exons are detected.
- Chromosomal rearrangements and nucleotide repeat expansions are not analyzed.
- Primary, Secondary* and Incidental* Findings are possible. *Opt-in/Opt-out options vary by lab.
- The likelihood of receiving uncertain or ambiguous results increases as the amount of genetic material analyzed increases.
- Pre-test counseling and informed consent is highly recommended.
- Many CLIA-certified genetic testing labs partner with third party biopharmaceutical companies to offer no-cost sponsored testing to patients who meet medical criteria.
- Clinical genetic testing is performed by the CLIA-certified test lab.
- A healthcare professional must confirm that patients have consented to the testing and meet certain criteria.
- Third parties and commercial organizations may receive the following information to identify individuals with (ultra) rare genetic diseases who meet clinical trial criteria:
- De-identified patient data (variant information and patient clinical features); and
- Healthcare provider contact information for research and/or commercial purposes.
Common Genetic Screens
- Determines fetal sex chromosomes and risk level for certain genetic abnormalities by analyzing small fragments of fetal DNA that circulate in a pregnant woman’s blood.
- Concerning NIPS results should be followed with post-test genetic counseling and diagnostic testing.
Practice Guidelines
- Noninvasive prenatal screening for fetal aneuploidy
- Screening for fetal aneuploidy and neural tube defects
Genetic Testing Tools in 2018
Dr. Austin Larson, a geneticist at Children’s Hospital Colorado, provided this overview of genetic tools and testing at the Indian Health Service Clinical Rounds on May 3rd, 2018. Cell-free Fetal DNA is covered at 29:00 of the webinar.
NOTE: No credentials are required to view this recording. If a pop-up box appears requesting your credentials, simply click “OK” and the recording will load on your browser.
- Screens for metabolic, endocrine, hemoglobinopathies, pulmonary, and immune disorders to identify newborns with certain serious medical conditions so they can begin treatment, preventing morbidity and mortality.
- Babies with concerning NBS results are referred for diagnostic testing
- In Wisconsin, NBS is required by law in order to protect the health of newborns.
Wisconsin Newborn Screening (NBS) Program: An Introduction
This CME-eligible activity is intended for pediatric clinicians who wish to improve their understanding of the NBS process, NBS rates, communication of NBS results with parent/guardians and making appropriate referrals. This activity was created by geneticists, genetic counselors, pediatricians, public health representatives and parents.
Target audience: MD, DO, RN, APRN, LPN, PA, Midwives, Genetic Counselors, Phlebotomists
Unique Circumstances
- A sudden unexplained death in the family is always tragic, but can be even more so when it occurs in an infant or young adult (≤45 years). Approximately 40% of sudden unexplained deaths in the young are caused by underlying genetic conditions. Autopsies are an important component to uncovering the cause of death, but up to 30% of the time no abnormalities are found in the heart. A molecular autopsy, or post-mortem genetic testing, can provide another opportunity to identify or confirm the cause of death.
- For more information including eligibility criteria, sample collection and storage, requisition form and family brochure, visit the Wisconsin State Lab of Hygiene Post-Mortem Genetic Testing webpage.
- The Sudden Death in the Young (SDY) Case Registry gathers information about young people who die suddenly and unexpectedly. Contributing information about a sudden unexplained death to the registry can help doctors, scientists, and families better understand and prevent these deaths. Contact the SDY Case Registry Data Coordinating Center for more information.
DNA banking is the secure storage of an individual’s DNA for future use. A small blood or saliva sample is taken, and then DNA is extracted and stored. Visit the Wisconsin State Lab of Hygiene DNA Isolation and Banking page for more information.
Nonclinical Genetic Testing: Direct-to-Consumer (DTC)
Direct-to-Consumer (DTC) genetic tests are marketed directly to customers via television, print advertisements, or the Internet, and the tests can be bought online or in stores. DTC genetic tests do not necessarily involve a healthcare professionals.