WHOLE MITOCHONDRIAL GENOME ANALYSIS WITH  HAPLOTYPING, and DELETION ASSAY

DESCRIPTION - Mitochondrial DNA Analysis

The Whole Mitochondrial Genome Scan is a comprehensive, sensitive test for mitochondrial diagnostics with the capability of detecting mtDNA variants and mutations (known and unknown) encompassing hundreds of disease-related mutations. Mitochondrial DNA (mtDNA) is a 16.5 kb circle of maternally inherited, extra nuclear, double-stranded DNA. It contains 37 genes encoding two ribosomal RNA’s, 22 transfer RNA’s and 13 subunits of the respiration chain. Mitochondrial disorders are associated with a heterogeneous set of clinical and pathological features. The variable age of onset, mode of presentation and rate of progression of many mitochondrial disorders makes diagnosis particularly difficult. This test reports on all heteroplasmic and homoplasmic mutations detected in the ENTIRE mitochondrial genome - including novel variants and polymorphisms.

This assay also detects large deletions, such as those associated with Pearson’s Syndrome, CPEO*, KSS*, and Maternally Inherited Deafness.

*SEE NOTE UNDER SPECIMEN REQUIREMENTS.

Haplotyping

In human genetics, Human mitochondrial DNA haplogroups are haplogroups defined by differences in human mitochondrial DNA. These haplogroups trace the matrilineal inheritance of modern humans back to human origins in Africa and the subsequent spread across the globe.  Various publications are indicating that these haplogroups are involved in reducing risk of PD, increasing longevity and some increased risk of cancer.

References:
1.Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD Angela Pyle, PhD 1, Thomas Foltynie, PhD, MRCP 2, Watcharee Tiangyou, BSc 1, Claire Lambert, BSc 1, Sharon M. Keers, BSc 1, Liesl M. Allcock, MRCP 3, Jill Davison, BSc 3, Simon J. Lewis, MRCP 2, Robert H. Perry, FRCP 4, Roger Barker, FRCP 2, David J. Burn, MD, FRCP 3 4 5, Patrick F. Chinnery, PhD, MRCP 1 5 * Annals of Neurology Volume 57 Issue 4, Pages 564 - 567 Published Online: 22 Mar 2005
2. Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males Authors: Nishigaki, Yutaka; Yamada, Yoshiji; Fuku, Noriyuki; Matsuo, Hitoshi; Segawa, Tomonori; Watanabe, Sachiro; Kato, Kimihiko; Yokoi, Kiyoshi; Yamaguchi, Sachiyo; Nozawa, Yoshinori; Tanaka, Masashi1 Human Genetics, Volume 120, Number 6, February 2007 , pp. 827-836(10)

 For a comprehensive listing of disease and conditions detected by the Whole Mitochondrial Genome Analysis, click here.

Whole Mitochondrial Genome Analysis with Haplotyping

Test Order Code MITO-WGA

CPT Codes

83891 x 1, 83892 x 20, 83898 x 21, 83894 x 1, 83903 x 20, 83904 x 80

 

Indications For Testing

  • Confirm diagnosis of affected individuals with;

  • Multi-systemic disorders involving neuromuscular, neurosensory, CNS, cardiac, renal, hepatic, GI, immune, endocrine systems, etc.

  • Family history of mitochondrial disorders

  • Matrilineal family members with known mitochondrial DNA mutations and asymptomatic carrier testing

  • Confirmation of mitochondrial mutations

Turn Around Time

 Less than four weeks. Expedited analysis is available upon request for an additional charge.
Specimen Requirements When looking for deletions indicative of KSS or CPEO, a muscle biopsy is the recommended specimen type because there is a higher detection of these deletions in muscle. We will accept a blood sample, however, a negative result in blood does not rule out the possibility of deletions indicative of KSS or CPEO. If a negative result is obtained from blood, we recommend having the test run on a muscle biopsy.

Ship one of the following:

Peripheral Blood
Peripheral blood collection requires a Lavender-top (EDTA) vaccutainer tube available in the DNA Specimen Collection Kit. Keep sample at ambient temperature and ship by overnight courier to arrive at the Molecular Laboratory within 24 hrs after collection of the specimen. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature.

  • Adults: 1 tube with 7.0 mL whole blood

  • Children & Infants: 1 tube with 5-6 mL whole blood

Muscle Biopsy
Tissue can be fresh or frozen, and must be shipped on dry ice.

  • Adults: 40-50 mg

  • Children: 25 mg

Specimen Kits DNA Specimen Collection Kits can be obtained from Transgenomic Molecular Laboratory.
Shipping and Contact Information Transgenomic Molecular Laboratory
12325 Emmet Street Omaha, NE 68164 USA
Phone: (866) 500-GENE / (866) 500-4363 Fax: (402) 452-5447
E-mail: labservice@transgenomiclabs.com
Test Submission  and Patient Consent Forms

Due to the unique nature of genetic testing, patients should receive pre-test and post-test counseling. Informed consent is recommended.

Test Methodology Whole mitochondria genome heteroplasmic mutations are detected by the WAVE® System using SURVEYOR® Nuclease and sequenced for confirmation. Homoplasmic mutations are deteced by bi-directional sequencing. Large deletions and duplications are amplified by expanded Long Range PCR (LR-PCR) and detected by gel electrophoresis.

Additional References

Mitomap
A human mitochondrial genome database.  http://www.mitomap.org/

Note: The performance characteristics of this test were validated by TRANSGENOMIC Molecular Laboratory. The U.S. Food and Drug Administration (FDA) has not approved this test. However, FDA approval is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. TRANSGENOMIC Molecular Laboratory is authorized under Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing.

TRANSGENOMIC MOLECULAR LABORATORY

Phone: (866) 500-GENE/ (866) 500-4363

FAX: (402) 452-5447