About

What is the Medical Genome?

The human genome is the complete set of DNA present in our cells. It includes our genes (or protein-coding regions, also known as the exome) which make up approximately 1-2% of the genome, and the non-coding regions, some of which control the genes and some of which currently have unknown function. Approximately 85% of pathogenic variants (mutations) known to cause disease occur in the genes (exome), while the rest are thought to be located in the non-coding regions. The Medical Genome test (i.e., whole genome sequencing or WGS) is a sequencing test for the whole genome (although there are still certain parts of the genome, about 10-15%, that cannot be sequenced with today’s technology).

Genome sequencing provides >98% coverage of the ~22,000 human genes and the non-coding regions (intragenic and intergenic) with a mean read depth of 30X. The Medical Genome analysis is performed using a tiered approach to identify pathogenic variants: first the ~5300 disease-associated genes and curated deep intronic and promoter pathogenic variants are analyzed, next the remaining ~16,700 genes are analyzed, then genomic and intragenic deletions and duplications are analyzed, followed by analysis of non-coding sequence regions. The Medical Genome analysis also includes selected class 1A pharmacogenetic targets.

The Medical Genome also features the Genome Slice Option, which allows clinicians to choose any gene panel relevant to the patient’s phenotype to ensure coverage of ALL exons of those genes, at no additional cost. Medical Genome sequence data without interpretation is also available as raw data files for clinical or research purposes.

Medical Genome

Why perform Medical Genome testing?

  • Medical Genome testing is meant to provide an answer faster by looking at the entire genome at one time vs. a single gene, or set of genes, over a longer period of time.
  • Studies show that Medical Genome testing is superior to the current tiered approach of testing, and identifies pathogenic variants in 35-40% of cases, drastically shortening the Diagnostic Odyssey experienced by many individuals with genetic disease and their families.

When is Medical Genome testing useful?

Medical Genome testing is helpful in the diagnosis of an affected individual when:

  • The patient had a negative Medical Exome (aka whole exome sequencing) test.
  • The patient’s symptoms or family history suggest a genetic etiology but does not correspond with a specific genetic disorder.
  • The patient has symptoms of a well-defined genetic disorder that is caused by multiple genes (genetic heterogeneity) for which a multi-gene panel is not clinically available.
  • The patient likely has a genetic disorder but previous clinical genetic testing did not yield a genetic diagnosis.
  • The patient’s clinical presentation is unclear/atypical and there are multiple genetic conditions in the differential diagnosis.

Why perform TRIO Medical Genome testing?

“TRIO” testing refers to testing the patient (aka proband) plus the patient’s biological parents. Testing all three family members at the same time can often help in interpreting variants found in the patient by determining if they came from the parents, and, if so, which parent. Testing the proband alone may lead to recommendations to test the parents for the variants found in the patient later.

What options are available for Medical Genome testing?

Test CodeTest DescriptionPatientCoverageTurnaround timeData Interpretation and Medical Report
GENOMEMedical Genome, with interpretation (one sample)Proband only30x6 weeks
GENOMETECHMedical Genome, no interpretation (one sample)Proband only30x2 weeks
GENOMETRIOMedical Genome, with interpretation (three samples)Proband + Parents30x6 weeks
GENOMETRIOTECHMedical Genome, no interpretation (three samples)Proband + Parents30x2 weeks
GENOMESTATMedical Genome, with interpretation (one sample) STATProband only30x10-12 days
GENOMESTATPLUSMedical Genome, with interpretation plus StepOne® Biochemical ProfileProband only30x10-12 days
GENOMETECHSTATMedical Genome, no interpretation (one sample) STATProband only30x10-12 days
GENOMETRIOSTATMedical Genome, with interpretation (three samples) STATProband + Parents30x10-12 days
GENOMETRIOSTATPLUSMedical Genome, with interpretation (three samples) STAT plus StepOne® Biochemical ProfileProband + Parents30x10-12 days
GENOMETRIOTECHSTATMedical Genome, no interpretation (three samples) STATProband + Parents30x10-12 days

TAT for StepOne is 3 calendar days. Click here to see StepOne details.

Additional Family Member can be ordered. However, the Medical Genome Trio should be ordered first or at the same time as the additional family members.
SAN - Sanger Confirmation Only
SANINT - Sanger Confirmation and Interpretation Only
REANAL – Medical Genome: Reanalysis and Reinterpretation (requires submission of clinical report)

Who can order the Medical Genome?
Medical Genome testing can only be ordered by a physician and results will only be reported to a physician.

  • If you are a physician, please download the Medical Genome Requisition Form. Fully complete the requisition form and Informed Consent form, including signatures of the physician and patient. Return forms with your patient’s sample.
  • If you are a patient, please download the Medical Genome Requisition Form. Bring form to your physician to fully complete and sign. Your signature is also required. If appropriate, your physician will collect your sample and send to PerkinElmer Genetics for testing.

How to Order

Specimen Requirements

For Medical Genome testing, samples are required from the proband (i.e., patient). For Medical Genome TRIOs, samples are required from proband and both biological parents. For other biological relatives, please contact PerkinElmer Genetics for more information. Please submit all samples at the same time.

Preferred Sample Types:

  • Saliva (Please note, the StepOne® biochemical profile cannot be performed on saliva samples)
  • Whole Blood (Please note, the StepOne biochemical profile cannot be performed on whole blood samples)
  • Dried Blood Spots (DBS)(Please note, DBS samples are needed for StepOne biochemical profile)

To order a PerkinElmer Genetics sample collection pack, please submit an order form by clicking here. Or call Toll Free: 1-866-463-6436.

Please contact the lab before submitting any other specimen type. For other sample types, please find more details by clicking here.

Special Instructions

Please submit medical records or clinical summary notes, a requisition form and a signed informed consent form when ordering Medical Genome testing. Testing will not be initiated until these documents are received. See below link to download the Medical Genome test requisition form and informed consent form:

Who can order the Medical Genome?
Medical Genome testing can only be ordered by a physician and results will only be reported to a physician.

  • If you are a physician, please download the Medical Genome Requisition Form. Fully complete the requisition form and Informed Consent form, including signatures of the physician and patient. Return forms with your patient’s sample.
  • If you are a patient, please download the Medical Genome Requisition Form. Bring form to your physician to fully complete and sign. Your signature is also required. If appropriate, your physician will collect your sample and send to PerkinElmer Genetics for testing.

Download Medical Genome Requisition Form

Methodology

The Medical Genome is performed on genomic DNA using the Illumina NovaSeq system, with 2x150bp basepair (bp) paired-end reads and an average coverage of 30X. The DNA sequence is mapped to, and analyzed in, comparison with the published human genome build UCSC hg19 reference sequence. The targeted coding exons and splice junctions of the known protein-coding RefSeq genes are assessed for the depth of coverage and data quality threshold values. The PerkinElmer proprietary Medical Genome bioinformatics analysis pipeline is used to compare sequence changes in the individual being tested to the reference sequence. All potential positive sequence variants in the proband are confirmed by conventional di-deoxy DNA sequence analysis (Sanger sequencing) using a separate DNA isolation.

The Medical Genome also features the Genome Slice Option, which allows clinicians to choose a PerkinElmer Genetics gene panel relevant to the patient’s phenotype to ensure coverage of ALL exons of those genes, at no additional cost.

Detection

The Medical Genome is innovative methodology and reports of clinical yield are insufficient to determine an accurate detection rate, although early reports indicate pathogenic variants are detected in 35-40% of cases.

FAQs

What is the Medical Genome?
The Medical Genome targets not only the protein-coding regions (exons) of the approximately 22,000 genes in the genome but also all introns and intergenic regions known to be associated with disease. It is a powerful diagnostic tool, providing a definitive diagnosis in ~21-59% of patients.

What is the difference between the Medical Genome (aka: whole genome sequencing - WGS) and Medical Exome (aka: whole exome sequencing - WES)?

  • The Medical Genome (i.e., whole exome sequencing) analyzes all genetic information present in an individual’s entire genome. This includes the entire genomic region of the genes (exons and introns) and intergenic regions known to be associated with diseases.
  • The Medical Exome (i.e., whole exome sequencing) sequences the entire exome. The exome is comprised of the regions within the genome that codes for proteins, called exons. It is estimated that the exome encompasses approximately only 1-2% of the genome, and contains approximately 85% of disease-causing pathogenic variants.
  • The Medical Genome is a more comprehensive test than the Medical Exome and enables the laboratory to detect types of changes that the Medical Exome cannot (e.g., copy number variations).

When is the Medical Genome (aka: whole genome sequencing) test useful?
The Medical Genome is useful when:

  • The patient had a negative Medical Exome (aka: whole exome sequencing) test.
  • The patient’s symptoms or family history suggest a genetic etiology but does not correspond with a specific genetic disorder.
  • The patient has symptoms of a well-defined genetic disorder that is caused by multiple genes (genetic heterogeneity) for which a multi-gene panel is not clinically available.
  • The patient likely has a genetic disorder but previous clinical genetic testing did not yield a genetic diagnosis.
  • The patient’s clinical presentation is unclear/atypical and there are multiple genetic conditions in the differential diagnosis.

How long does it take to get my patient’s results for the Medical Genome?
The turnaround time (TAT) is measured from sample receipt to delivery of the results report. This assumes that all required paperwork is completed fully and accurately at the time of sample submission. The TAT for the Medical Genome is 42 calendar days.
Documents needed are:

Can I get my Medical Genome results faster than the stated turnaround time (TAT)?
Arrangements may be made for results to be returned STAT if required for urgent medical management. Medical interpretation and report may be provided STAT within 10-12 calendar days after the sample has been sequenced. There is an additional charge for STAT orders. For pricing, please email PerkinElmer Genetics or call us at 866-463-6436. Please indicate STAT testing by checking the Medical Genome STAT testing in the Whole Genome Sequencing Requisition Form
STAT options include:

  • GENOMESTAT: Medical Genome, with interpretation STAT
  • GENOMESTATPLUS: Medical Genome, with interpretation (includes StepOne® Biochemical Profile) STAT
  • GENOMETECHSTAT: Medical Genome, no interpretation STAT
  • GENOMETRIOSTAT: Medical Genome Trio, with interpretation STAT
  • GENOMETRIOSTATPLUS: Medical Genome Trio, with interpretation plus StepOne® Biochemical Profile STAT
  • GENOMETRIOTECHSTAT: Medical Genome Trio, no interpretation STAT

Can I submit a sample for the Medical Genome without an order from a health care provider?
No, Medical Genome testing must be ordered by a physician and results will only be reported to a physician.

What specimens are acceptable for Medical Genome testing?
Strongly preferred sample types for Medical Genome testing are dried blood spot (DBS), saliva, and whole blood (EDTA/purple top tube).

What is the price for the Medical Genome?
For pricing, please email PerkinElmer Genetics or call us at 866-463-6436.

Does PerkinElmer Genetics accept insurance or file for insurance directly?
At this time, PerkinElmer Genetics accepts only institution bill accounts or testing paid in-full by the patient at the time of testing.

Does PerkinElmer Genetics offer Medical Genome sequencing without medical interpretation?

  • Yes, we offer sequencing of the patient sample without medical interpretation.
  • To obtain sequencing results only, please indicate on the Whole Genome Sequencing Requisition Form
  • Sequencing only options include:
    • GENOMETECH: Medical Genome, no interpretation
    • GENOMETRIOTECH: Medical Genome Trio, no interpretation
    • GENOMETECHSTAT: Medical Genome, no interpretation STAT
    • GENOMETRIOTECHSTAT: Medical Genome Trio, no interpretation STAT

Does PerkinElmer Genetics offer reanalysis of Medical Genome data and what is the cost?

  • Yes, we offer reanalysis of genome data.
  • We recommend waiting 6-12 months after the initial test was reported to allow additional curation of new research/clinical information.
  • Turnaround time: 7-14 calendar days
  • For pricing, please email PerkinElmer Genetics or call us at 866-463-6436.

How much of the whole genome is covered with the Medical Genome?

  • The Medical Genome covers ~85% of the genome
  • The Medical Genome covers >98% of all coding regions

Can we have access to the raw data? E.g., BAM, FastQ, VCF?
The raw data generated can be requested by the ordering health care provider.

What is reported in the Medical Genome test?

  • Variants that are known to be pathogenic or for which the laboratory has sufficient evidence suggesting pathogenicity in a gene that is suspected to cause the patient’s signs/symptoms.
  • Predicted mutation(s) in a gene, which is potentially related to the phenotype but for which a specific clinical phenotype has not been previously well defined
  • Variants of uncertain clinical significance in genes known to be associated with disease and genes not known currently associated with a disease (new genes) related to the patient’s phenotype.
  • Variants that are pathogenic or for which the laboratory has sufficient evidence suggesting pathogenicity in a gene that is medically significant but unrelated to the patient’s presenting symptoms, unless the patient or parent/guardian declines this information.

Are there any genes/regions that will not be reported?

  • A fraction (~10%) of the exome cannot be sequenced to accurately determine if a pathogenic variant is present. Therefore, pathogenic variants in these regions will not be detected by this analysis.
  • The technology that sequences the Medical Genome (i.e., next generation sequencing (NGS)) cannot accurately sequence repetitive regions, such as trinucleotide repeats. This means that NGS cannot provide data on regions such as the fragile X syndrome repeat region, the Huntington disease repeat region, or the myotonic dystrophy repeat region.
  • Results from the Testing may indicate that additional testing, such as full gene sequencing to complete exons with poor coverage or deletion/duplication analysis, is recommended.
  • Genetic changes identified may not necessarily predict the prognosis or severity of disease and it is possible that the genetic change may not affect management or treatment.
  • Mitochondrial genome mutations, genes with pseudogenes, and epigenetic defects may not be detected by this test.

How does PerkinElmer Genetics handle reporting of incidental findings?
Adult patients and family members are given options in the informed consent form to indicate what type of results should be delivered. Options to opt-in for any of the following are provided:

  • Pharmacogenetic variants: Pharmacogenetic variants are changes in the DNA that do not cause a disease but may be related to how your body processes certain medications, such as chemotherapy drugs, antipyretics, antidepressants, anticoagulants, and others. These variants may not be important to you if you are not taking the medications involved, but may tell you how well the medications will work or if you will have side effects if you do take the medications now or in the future.
  • Carrier Status for Autosomal Recessive Conditions (ex. cystic fibrosis) A recessive condition is one in which two pathogenic variants in the same gene are required in order to show symptoms of the disease (one variant is inherited from each parent). Someone who has only one pathogenic variant does not show symptoms and is called a carrier. However, if we find a pathogenic variant in a recessive gene that is related to the patient's disease, we will report it as a diagnostic finding. Further testing may be necessary to look for a second pathogenic variant in that gene not identified by WES. You can choose whether or not you want us to report carrier status in genes that are not related to the patient's disease. The Testing is not designed to be a comprehensive carrier test. We are unable to guarantee that all conditions for which the individual is a carrier will be determined by the Testing. An individual may be a carrier for a condition in which there was little or no coverage in the Testing and therefore will not be detected. Additional carrier testing for reproductive purposes should be discussed with your doctor or genetic counselor.
  • Diagnostic findings in adult onset medically-actionable disorders not related to disease: Medically-actionable conditions are those for which there is currently recommended treatment or preventative actions that can be taken to reduce the risk of developing the disease. An example would be hereditary cancer syndromes such as Lynch syndrome. We are unable to guarantee that the Testing will find all adult onset medically-actionable conditions for which the individual has a pathogenic variant. An individual may have a pathogenic variant for a condition in which there was little or no coverage in the Testing and therefore will not be detected. Additional testing for health purposes should be discussed with your doctor or genetic counselor.
  • Diagnostic findings in adult onset currently medically non-actionable disorders not related to disease: Conditions that are not currently medically-actionable do not have recommended treatment or preventative measures. An example would be Alzheimer's disease. We are unable to guarantee that the Testing will find all adult onset medically non-actionable conditions for which the individual has a pathogenic variant. An individual may have a pathogenic variant for a condition in which there was little or no coverage in the Testing and therefore will not be detected. Additional testing for health purposes should be discussed with your doctor or genetic counselor.

Will PerkinElmer Genetics Medical Genome detect mitochondrial disease?

  • Mitochondrial diseases can be caused by mutations in either the mitochondrial genome (a small circular chromosome found within the mitochondria) or by mutations in the nuclear genome (on the chromosomes found in the nucleus). Whole genome sequencing is typically done in such a way that only the exons in the nuclear genome are captured and fully sequenced, and thus, will identify most but not all of the mutations associated with mitochondrial disease.
  • We are not capturing the entire mitochondrial genome as, with our experience, the yield is less than 1% and has low clinical utility.
  • Our assay does, however, include common point mutations in the mitochondrial genome associated with diseases such as LHON, MERRF, and NARP.
  • If you would like to discuss mitochondrial sequencing, please email PerkinElmer Genetics or call us at 866-463-6436 for more information.

Do you perform confirmation of mutations that are detected by the Medical Genome?
Yes.

Can PerkinElmer Genetics detect single exon deletions and duplications?
Yes.

Can PerkinElmer Genetics Medical Genome detect large rearrangements like multi-gene deletions and duplications?
Yes.

What sequencing platform do we use for whole genome sequencing?
PerkinElmer Genetics uses the latest sequencing platforms from Illumina. We utilize the NovaSeq to generate sequencing data for the Medical Genome.

How do I order sample collection kits?

  • DBS collection packs can be ordered through customer service or via an email.
  • Saliva or whole blood collection packs are currently not available. Once they become available they can be ordered in the same manner.

References

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  2. Taylor, J et. al. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nature Genetics 47, 717–726 (2015)
  3. Gilissen C., Hehir-Kwa J.Y., Thung D.T. Genome sequencing identifies major causes of severe intellectual disability. Nature. 2014; 511:344–347
  4. Belkadi A., Bolze A., Itan Y. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc Natl Acad Sci U S A. 2015; 112:5473–5478
  5. Saunders C.J., Miller N.A., Soden S.E. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med. 2012; 4:154
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  7. The 100,000 Genomes Project. 2014. Accessed January 10, 2015.
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  9. Hegde M, et. al. Development and Validation of Clinical Whole-Exome and Whole-Genome Sequencing for Detection of Germline Variants in Inherited Disease. Arch Pathol Lab Med. 2017 Mar 31.
  10. Zornitza, S, Schofield, D. Prospective comparison of the cost-effectiveness of clinical whole-exome sequencing with that of usual care overwhelmingly supports early use and reimbursement. Genetics in Medicine. 2017. doi:10.1038/gim.2016.221
  11. Lupski, J et. al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med. 2010 April 1; 362(13): 1181–1191
  12. Biesecker, LG and Green, RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370:2418-25.
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