Genetics: More Than 23 and Me

Transcription

1 Genetics: More Than 23 and Me Stephanie J. Offord, FNP-BC, AGN-BC, MSN Gina Lewis, CPNP-PC, MSN Suzanne Ducett, BSN, RN Interactive questions in presentation. Text NPGENETICS123 to once to join

2 DISCLOSURE

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8 Objectives Why Genetics is relevant in Medicine State of Genetics Children s Hospital of WI clinic model Genetics relevance for all Nurses The ABCs of Genetics Central dogma of genetics Basics of genetic testing Inheritance Patterns and Pedigrees Genetics referrals and resources Future of Genetics Direct to Consumer Testing Pharmacogenomics

9 Why is Genetics Relevant?

10 Genetics in Medicine Diagnosis Prevention Treatment

11 Former President Obama announced Precision Medicine Initiative

12 Precision Medicine An emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person NIH Precision Medicine Initiative

13 Genetics vs Genomics Genetics refers to the study of single genes and inherited characteristics Genomics is the study of the function and combined influence of all genetic sequences World Health Organization, 2015

14 State of Genetics Critical Shortage

15 Who are Geneticists and Genetic Counselors? Geneticist Board certified physician in Genetics Genetic counselor Master of Science in Genetic Counseling Genetic counselors receive special training in two areas - genetics and counseling

16 Children s Hospital of Wisconsin Genetics Model

17 What is a Nurse Clinician? The Clinician has advanced clinical knowledge and skill to partner with members of the healthcare team to assess, plan and provide nursing care to individuals and groups. The Clinician is a recognized resource and consultant to healthcare providers, within Children s Hospital and Health System (CHHS) and the community at large. -Children s Hospital of Wisconsin

18 How do you achieve advanced clinical knowledge? Comprehensive 9 week genetic education alongside the Nurse Practitioners Attend conferences yearly Seek out individual education where needed (Metabolic University, attend Conferences) Participate in monthly Journal clubs Attend registry meetings IRB certification (Research) Grand rounds weekly

19 Why was there a need to bring a Nurse Clinician into Genetics? The Genetic Counselors out of necessity were working out of their scope of practice in regards to medication management, triaging of medical illnesses, and overall general medical management The new model was bringing four additional Nurse Practitioners on board necessitating an increase in support to their role

20 Role of the Genetics Nurse Clinician Two Nurse Clinicians support the clinic Involved with clinic visits in conjunction with Physicians, Nurse Practitioners, Genetic Counselors, and Registered Dieticians Large volume of medication management-as well as infusion management Phone triage Assist with punch biopsies Prior-Authorizations Aide in the planning of NF symposiums Coordinate muscle biopsy rounds Participate in ongoing research projects Trouble shoot everything and anything!

21 Types of Clinics within Genetics Connective Tissue General Genome Metabolic RASopathies (ie; NF & Noonan syndrome) Research Achondroplasia Connective Tissue Fabry Disease

22 How does this impact you?

23 Genetics in Practice Cardiology Infectious Disease Heme/ Onc Pharma Pulm Neurology Renal Rheum GI

24 Lack of Genetic Training Studies over the last 15 years showed little change in the knowledge levels of nurses in genetics and genomics. Journal for Nurses in Professional Development 2017 No discipline has evolved more quickly than genomics, and so many nurses and NPs report feeling ill-prepared to engage because they believe their baseline preparation and knowledge is weak. The Nurse Practitioner 2014

25 Objectives Why Genetics is relevant in Medicine State of Genetics Children s Hospital of WI clinic model Genetics relevance for all Nurses The ABCs of Genetics Central dogma of Basics of genetic testing genetics Inheritance Patterns and Pedigrees Genetics referrals and resources Future of Genetics Direct to Consumer Testing Pharmacogenomics

26 DNA RNA Proteins

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31 DNA RNA Proteins

32 What s in the code

33 What s in the code?

34 Genetic Testing

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37 Karyotype (Chromosome Analysis) Detects numerical chromosomal differences Detects large chromosomal rearrangements

38 Fluorescence In Situ Hybridization (FISH) Quicker detection of numerical chromosomal differences Utilizes Probes to detect small changes

39 Possible Chromosomal Variations

40 Chromosome Variations May Involve: Changing the structure of a chromosome The loss or gain of part of a chromosome Types of Variations Deletion Duplication Inversion Translocation Nondisjunction

41 Deletion

42 Duplication Occurs when a gene sequence is repeated

43 Inversion Occurs when a part of a chromosome is flipped upside down

44 Involves two chromosomes that aren t homologous Part of one chromosome is transferred to another chromosome Translocation

45 Nondisjunction Failure of chromosomes to separate during meiosis

46 Chromosome Microarray Detects deletions and duplications

47 Possible Results Pathogenic Disease-causing The copy number variant identified is known to cause a genetic condition Benign Harmless The copy number variant does not cause disease Variant of Uncertain Significance Copy number variants with too little data to classify as either pathogenic or benign It is unknown whether this copy number variant causes a medical condition

48 Why is a microarray important?

49 Single Gene Testing Single genes can be tested with a variety of methodologies

50 Multigene Panel

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52 Exome vs Genome Sequencing Whole exome sequencing scans all of the EXONS of all genes looking for DNA variants Whole genome sequencing scans ALL of the genetic code

53 Cell-Free Fetal DNA Prenatal screen that utilizes fetal DNA circulating in maternal blood from placental cells

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55 Inheritance Patterns and Pedigrees

56 Autosomal Dominant Inheritance

57 Autosomal Recessive Inheritance

58 X-Linked Recessive Inheritance

59 Mitochondrial Inheritance

60 Objectives Why Genetics is relevant in Medicine State of Genetics Children s Hospital of WI clinic model Genetics relevance for all Nurses The ABCs of Genetics Central dogma of genetics Basics of genetic testing Inheritance Patterns and Pedigrees Genetics referrals and resources Future of Genetics Direct to Consumer Testing Pharmacogenomics

61 Reasons for a Genetics referral Multiple congenital anomalies Developmental delay Autism Dysmorphic facial features Unusual growth pattern Overgrowth, short stature, or hemihyperplasia Family History Consanguinity Cognitive delays, developmental disability, inherited disorder, birth defects, or early deaths

62 Genetics Resources GeneReviews Online Mendelian Inheritance in Man (OMIM) Genetic and Rare Diseases Information Center (GARD) Genetics Home Reference Unique

63 Genetics Facilities National Society of Genetic Counselors American College of Medical Genetics MG/ISGweb/FindaGeneticService.aspx Genetic Testing

64 Objectives Why Genetics is relevant in Medicine State of Genetics Children s Hospital of WI clinic model Genetics relevance for all Nurses The ABCs of Genetics Central dogma of genetics Basics of genetic testing Inheritance Patterns and Pedigrees Genetics referrals and resources Future of Genetics Direct to Consumer Testing Pharmacogenomics

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66 Direct to Consumer Testing

67 Direct to Consumer Testing Companies that sell genetic testing directly to a patient independent of their physician Can inform on medical conditions accidentally or give false reassurance This is not full gene sequencing

68 Direct to Consumer Testing Biocompatibility Testing HLA Testing Neurocompatibility Testing Serotonin Transporter Psychological Compatibility Questionnaire

69 Direct to Consumer Testing

70 What s the harm? What can it tell me about my health? Nothing!!! This is not full testing Can offer false reassurance Cannot take test results to a provider for interpretation.

71 MTHFR Methylenetetrahydrofolate reductase gene The MTHFR gene is involved in the folate metabolism pathway Once upon a time, variants in the MTHFR gene were thought to be linked to more than 400 diseases, but the mainstream scientific community now thinks otherwise. Current scientific literature indicates that the impact of the two common MTHFR variants (C677T and A1298C) is minimal and clinically insignificant. In the US up to 40% of white and Hispanic individuals have one copy of the C677T variant. Up to 20% of the population have two copies of the C677T variant

72 What impact does this have on Direct to Consumer testing? Although research has supported that the test for MTHFR is not very useful, it has become a popular test for naturopaths, homeopaths, and alternative medicine companies. Several direct-to-consumer DNA testing labs screen for MTHFR variations. Supplement companies and alternative medicine maintain that MTHFR variations could be the key to everything from fatigue, blood clotting disorders, Alzheimer s, to schizophrenia & cancer.

73 Our Thoughts Despite lots of research and lots of buzz the existing scientific data doesn t support the vast majority of claims that common MTHFR variants impact human health. Based on the existing data, scientists at 23andMe have concluded that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health.

74 Pharmacogenomics

75 Pharmacogenetics Study of how a person s genetic makeup can affect their response to a drug. Used to help decide appropriate treatment for each individual Choosing a drug more likely to work Avoiding drugs with side effects Adjusting the dose of a drug Need for closer monitor

76 Pharmacogenomics

77 CYP enzymes

78 Sample Results Right Patient Right Drug (RPRD) 1200 genes (not all listed on the report) 95% of data is not on report Table 1 Considered medically actionable Evidence based guidelines Clinical Pharmacogenetics Implementation Consortium

79 Table 2 Clinically relevant variants of interest Evidence that these genes play a role in medication metabolism No evidence based guidelines Sample Results

80 Sample Results Table 3 Known pharmacogenetic functions No CPIC guidelines or other treatment guidelines Emerging as potential genes

81 Limitations of Pharmacogenomics One single pharmacogenetic test cannot be used to determine response to all medications One medication in one pathway Only available for a small subset of medications Reimbursement for testing and counseling is limited Field of pharmacogenomics is still in its infancy Only 4-5 pharmacy schools in the country have residencies in pharmacogenomics MCW is working on adding pharmacogenomics to curriculum

82 Thank You

83 Questions

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