application for specialty certificate...application for specialty certificate upon completion,...

Application for Specialty Certificate

Upon completion, please forward this application for a new or modified specialty certificate to Lois Margaret Nora, MD, JD, MBA, ABMS President and Chief Executive Officer, in care of David B. Swanson, PhD, at [email protected]. If you need any assistance with the completion of this application, please contact Jim Arcuri, Coordinator, Program Review, at [email protected].

1. Provide the name of the proposed new or modified specialty certification:

Laboratory Genetics and Genomics

2. State the purpose of the proposed new or modified specialty certification in one paragraph or less:

The proposed specialty of Laboratory Genetics and Genomics (LGG) is not a new unique area of focus, but rather a systematic merger of two existing primary specialties of the ABMGG: clinical cytogenetics and genomics (referred to in this document as CGG or cytogenetics) and clinical molecular genetics and genomics (MGG or molecular genetics). This transition from two to one specialty certificate is driven by advances in diagnostic technology over the last 10-15 years that coalesces cytogenetics and molecular genetics testing and application. The ABMGG and its professional society recognize that the expertise required of our diplomates has changed and that merging the specialties is essential to advance clinical care. Not surprisingly, the ABMGG has begun to see a decline in individuals seeking certification in cytogenetics alone and an increase in the number seeking dual certification in cytogenetics and molecular genetics. Following this new integrated training, diplomates in LGG would offer comprehensive genetic and genomic results and interpretation, and will be uniquely poised to discuss the relevance of each component of testing performed, informing the healthcare team and leading to the most appropriate next best steps in the care of patients. Subsequent to finalization of this specialty, the ABMGG will no longer offer board certification in CGG or MGG alone (following completion of the current candidates or trainees).

3. Document the professional and scientific status of this special field by addressing (a) through (e) below.

a. In the space provided, please describe how the existence of a body of scientific medical knowledge underlying the proposed new or modified specialty area is in large part distinct from, or more detailed than, that of other areas in which certification is offered:

For the diagnosis of individuals with hereditary or congenital disorders and certain cancers, genetic testing historically has included cytogenetic analysis of chromosome structure and function in certain cases or of DNA sequence variation. These methods have been used in genetic testing for several decades, but remained separate due to specific clinical needs, non-overlapping technologies, and specialized training of laboratory geneticists. However, the last 5 to 10 years have witnessed dramatic advancements in DNA testing technologies, specifically whole genome microarray analysis and next-generation DNA sequencing. These technologies allow interrogation on a very broad scale, from analysis of whole chromosomes to identification of individual nucleotides. As a result, they are quickly becoming integrated into the clinical genetics and genomics laboratories and clinical practice, becoming standard first-tier tests for certain classes of hereditary conditions due to much improved diagnostic yield and rapidly declining cost of testing. A single technology such as whole exome sequencing can be used to diagnose chromosomal aneuploidies (e.g. Down syndrome) and chromosomal micro-deletions/-duplications (e.g. Williams syndrome) as well as classical, genetic conditions (e.g. cystic fibrosis, syndromic intellectual disability). Moreover, there are many disorders where the underlying molecular basis may either be a large gene deletion or rearrangement or single nucleotide variant (e.g. Duchenne muscular dystrophy). Laboratory evaluation of both chromosome copy number variations and single nucleotide variants in the diagnosis of most genetic disorders significantly improves the diagnostic rate and reliability of the diagnosis, benefitting the profession and public society. Accredited training and ABMGG board certification has successfully supported the growth of laboratory professionals in cytogenetics and molecular genetics for 25 years (over 30 years in cytogenetics and 25 years in molecular genetics). The body of scientific medical knowledge in these two areas has expanded greatly with the discovery of novel microdeletion syndromes and Mendelian disorders, recognition of disorders caused by both chromosomal and sequence changes, and evidence of high clinical utility of exome sequencing. In addition, the rapid decline in the cost of

genetic diagnostic technology and rapid increase in the speed, amount and reliability of the data generated has made affordable large scale technologies that bridge the traditional domains of cytogenetics and molecular genetics thus bringing these two specialties together. The proposed new specialty in LGG is a merger of the accredited training and board certification of the ABMGG primary specialties in cytogenetics and molecular genetics and hence the scope of expertise for these diplomates. It is not distinct from the two current specialties, but recognizes that these fields are not distinct in current practice. The merged specialty will allow for these diplomates to provide more comprehensive laboratory results and interpretation to clinicians leading to better care to patients with these conditions.

b. Explain how this proposed new or modified specialty addresses a distinct and definable patient population, a definable type of care need or unique care principles solely to meet the needs of that patient population:

Cytogenetic testing by microarray analysis is a first-tier test for individuals with neurological disorders, developmental delay, or syndromic congenital anomalies, with a clinical yield of ~15%. Prenatal testing also routinely includes microarray analysis. In fact, the American College of Obstetricians and Gynecologists (ACOG) recommends that mircroarray be offered to women undergoing an invasive test (details at http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Genetics/The-Use-of-Chromosomal-Microarray-Analysis-in-Prenatal-Diagnosis; December 2013). Exome sequencing is also proving extremely useful with a ~25% clinical yield in diagnosing individuals with idiopathic disorders.

c. To provide COCERT with information about the group of physicians concentrating their practice in the proposed new or modified specialty area, please indicate the following:

i. The current number of such physicians (along with the source(s) of the data):

ABMGG certification has been offered in cytogenetics since 1982 and in clinical molecular genetics since 1990. There have been a total of 772 diplomates boarded in CGG since 1982. Since 1990, there have been 467 CGG certificates granted and 683 MGG certificates. The following table, compiled from the ABMGG certification statistics, show the number of diplomates boarded in either CGG, MGG or both primary specialties since 1990. Diplomates (1990-2015): CGG: 279 MGG: 421 CGG & MGG: 190

ii. The annual rate of increase of such physicians in the past decade (along with the source(s) of the data):

The ABMGG offers its certification examinations biennially. Candidates who have completed training in both specialties might sit for one of the specialty examinations or both at the same time or different years. Since the examinations are given biennially (beginning in 2005), this demonstrates the year when certified in the second specialty. # of Diplomates Year CGG MGG CGG and MGG 2005* 23 47 20 2007 21 27 21 2009 21 34 19 2011 18 46 26 2013 22 35 45 2015** 25 51 49 *prior to 2005, the certification examination was given every three years rather than every two, so the numbers listed in 2005 included three years worth of candidates. **Some of those listed in CGG and MGG will likely take the complementary exam in 2017. We anticipate that the dual-boarded CGG/MGG number in 2015 will increase and those with single certifications will decrease.

iii. The current geographic distribution of this group of physicians, its projected spread in the next five (5) years, and an explanation of how you arrived at this projection:

We do not anticipate increases in the number of diplomates in the merged specialty compared to those we currently certify. This is not anticipated to any change in geographic distribution nor impact on access, since these are laboratory geneticists and not providing direct patient care.

d. For COCERT, please identify the existing national societies, the principal interest of which is in the proposed new or modified specialty area:

There is one medical/clinical specialty society, the American College of Medical Genetics and Genomics (ACMG) that represents the overall practice and interests of diplomates of the ABMGG. The mission of the ACMG (from www.acmg.net) is: Developing and sustaining genetic and genomic initiatives in clinical and laboratory practice, education and advocacy. These are the three guiding pillars of the Strategic Plan. (1) Clinical and Laboratory Practice: Establish the paradigm of genomic medicine by issuing policy statements and evidence-based or expert clinical and laboratory practice guidelines and through descriptions of best practices for the delivery of genomic medicine; (2) Education: Provide education and tools for medical geneticists, other health professionals and the public and grow the genetics workforce. (3) Advocacy: Work with policymakers and payers to support the responsible application of genomics in medical practice.

i. Indicate the existing national societies’ size and scope, along with the source(s) of the data:

Currently there are 1146 full fellows of the ACMG (a fellow in the College is required to be an ABMGG diplomate) with an additional 730 individuals in other membership categories. (data from ACMG, November 2015).

ii. Indicate the distribution of academic degrees held by their members, along with the source(s) of the data:

The following are the degrees of the current fellows of the ACMG (data from ACMG Membership Office, November 2015): MD (or equivalent): 510 PhD: 468 MD/PhD: 168

iii. Indicate the relationship of the national societies’ membership with the proposed new or modified specialty area:

The ACMG leadership has been a strong advocate and driver for merging the two current specialties into the new proposed discipline of LGG. As with the current diplomates, those certified in LGG will be eligible to apply to become fellows in the College and will be encouraged to do so. There is no anticipated change in their advocating and supporting the professional activities of these diplomates, as they do for the current CGG and MGG diplomates.

e. For the entities described below, please provide the number of those who have a primary educational effort devoted to the proposed new or modified specialty area, along with their geographic locations and the source(s) of the data:

i. Medical schools:

39. Since a section of the ABMGG currently accredits the CGG and MGG laboratory training programs, the numbers

for this section comes directly from the Board. The training programs for CGG and MGG are typically housed in academic medical centers, with the exception of three: Greenwood Genetic Center, Henry Ford Hospital, and NHGRI/NIH. Beyond being reflective of academic medical center locations, there is no specific geographic bias as to where programs are located.

ii. Hospital departments:

1 (One). Since a section of the ABMGG currently accredits the CGG and MGG laboratory training programs, the numbers for this section comes directly from the Board. The training programs for CGG and MGG are typically housed in academic medical centers, with the exception of three: Greenwood Genetic Center, Henry Ford Hospital, and NHGRI/NIH. Beyond being reflective of academic medical center locations, there is no specific geographic bias as to where programs are located.

iii. Divisions:

N/A

iv. Other (please specify):

2. Since a section of the ABMGG currently accredits the CGG and MGG laboratory training programs, the numbers for this section comes directly from the Board. The training programs for CGG and MGG are typically housed in academic medical centers, with the exception of three: Greenwood Genetic Center, Henry Ford Hospital, and NHGRI/NIH. Beyond being reflective of academic medical center locations, there is no specific geographic bias as to where programs are located.

4. Please list the number and names of institutions providing residency and other acceptable educational programs in the proposed new or modified specialty area:

There are currently 42 programs that are accredited to provide clinical laboratory training in both cytogenetics and molecular genetics. We anticipate that all of these programs will become accredited in LGG. These are listed in order of the State wherein the programs reside. [Data from the ABMGG Accreditation Site, as of November 2015] 1. University of Alabama, Birmingham - Birmingham, AL 2. Stanford University School of Medicine - Stanford, CA 3. UCLA Intercampus Medical Genetics Training Program - Los Angeles, CA 4. UCSD School of Medicine - San Diego, CA 5. UCSF School of Medicine - San Francisco, CA 6. University of Colorado School of Medicine - Denver, CO 7. Yale University School of Medicine - New Haven, CT 8. Univ. of Miami School of Medicine/Jackson Memorial Hosp - Miami, FL 9. Emory University School of Medicine - Atlanta, GA 10. University of Chicago - Chicago, IL 11. Indiana University School of Medicine - Indianapolis, IN 12. Tulane University School of Medicine - New Orleans, LA 13. The Johns Hopkins University School of Medicine - Baltimore, MD 14. National Human Genome Research Institute/NIH - Bethesda, MD 15. Harvard Medical School & Boston Children's Hospital - Boston, MA 16. Henry Ford Hospital - Detroit, MI 17. University of Michigan School of Medicine - Ann Arbor, MI 18. Wayne State University School of Medicine - Detroit, MI 19. Mayo Clinic - Rochester, MN

20. University of Minnesota School of Medicine - Minneapolis, MN 21. University of Missouri - Kansas, City, MO 22. Washington University School of Medicine - St Louis, MO 23. University of Nebraska Medical Center - Omaha, NE 24. Rutgers New Jersey Medical School - Newark, NJ 25. Albert Einstein College of Med./Montefiore Medical Center - Bronx, NY 26. Columbia University Medical Center - New York, NY 27. Icaan School of Medicine Mt. Sinai - New York, NY 28. Duke University School of Medicine - Durham, NC 29. University of North Carolina School of Medicine - Chapel Hill, NC 30. Cincinnati Children’s Hospital Medical Center - Cincinnati, OH 31. Nationwide Children’s Hospital and Ohio State University - Columbus, OH 32. University Hospitals Case Medical Center/Case Western Reserve University Center for Human Genetics - Cleveland, OH 33. University of Oklahoma Health Sciences Center - Oklahoma City, OK 34. Oregon Health & Science University - Portland, OR 35. Children's Hospital of Philadelphia [CHOP] & University of Pennsylvania School of Medicine - Philadelphia, PA 36. University of Pittsburgh School of Medicine - Pittsburgh, PA 37. Greenwood Genetic Center - Greenwood, SC 38. Baylor College of Medicine - Houston, TX 39. University of Utah School of Medicine - Salt Lake City, UT 40. Virginia Commonwealth University School of Medicine - Richmond, VA 41. University of Washington School of Medicine - Seattle, WA 42. University of Wisconsin-Madison School of Medicine - Madison, WI

a. Indicate the total number of trainee positions available currently (along with the source(s) of the data):

The number of trainee positions available is compiled by the programs. However, most programs accept between 1-5 trainees in CGG or MGG per year, based on the number of trainees completing training. We do not anticipate a significant change in the number of accredited clinical fellowships because of the merger of the current specialties.

b. Provide the number of trainees completing the training annually (along with the source(s) of the data):

The range of the number of trainees completing training annually in CGG or MGG are listed below (data from ABMGG Administrative Office). This would include those who train in both specialties. All trainees are registered with the Board when beginning and completing training. Estimate of trainees completing training annually based on 2013-1015: year # completing cyto molecular both finished training only only cyto & mol 2015 60 4 37 19 2014 46 11 26 9 2013 62 15 39 8

c. Describe how the numbers of training programs and trainees are adequate to:

i. Sustain the area of specialization:

There are currently 42 programs accredited to train fellows in both clinical cytogenetics and genomics and clinical molecular genetics and genomics. We do not anticipate that number to change with the merger of these primary specialties into one (LGG). This proposal is focused not on adding more training programs but rather on integrating these two existing primary specialties in order to better prepare fellows for the demands of a career in clinical laboratory genetics and genomics (LGG). Over the next few years, meeting this professional need will require competency and proficiency in both cytogenetics and molecular genetics. Neither specialty is sustainable on its own, nor do we believe this should be the case. Furthermore, because fellows will now train in a well-integrated two year specialty (instead of the current model, which requires three years to specialize in two separate areas), we can train

more qualified laboratorians in an area of medicine that is increasing in demand and that, in turn, demands the abilities of very highly-skilled individuals.

ii. Allow for a sustained critical mass of trainees necessary for trainee testing validity and training program accreditation:

The number of candidates who seek board-certification in only clinical cytogenetics has been in decline over recent years, and reflects the evolution of the field as one that incorporates an increasing number of molecular technologies. Conversely, interpretation of molecular data is limited when laboratorians lack the ability to view the genome from a chromosomal perspective. Acquiring this perspective, as well as an understanding of technologies that afford targeted single cell analysis (FISH) and accurate genomic copy number changes (microarrays), facilitates an understanding of genomic mechanisms of disease. As we train fellows to move fluidly between these two fields, the board-certification process should be more appropriately tailored to the work our diplomates are doing on a daily basis. Increasingly that work requires a solid foundation in both cytogenetics and molecular genetics and proficiency in the major technologies and their respective applications. The number of diplomates who were initially boarded in a single one of these specialties but who have since returned to complete the second fellowship is growing, which reflects the growing clinical need for integrated training that brings together these two specialties of genetics. Finally, more individuals taking a single integrated certification exam will allow for an exam that is more representative of the knowledge base required for daily practice and will also lead to a certification examination that is more robust statistically because of the higher numbers of individuals sitting for the single specialty.

5. Please provide the number and type of additional educational programs that may be developed based on this proposed new or modified specialty area. Please indicate how you arrived at that number:

As noted previously, there are currently there are 42 institutions spread across the United States that offer fellowship training in both clinical cytogenetics and genomics and clinical molecular genetics and genomics (see http://www.abmgg.org/pages/training_accredprog.shtml). Additionally, there are two programs that currently are accredited in only cytogenetics. Both of these institutions have ACGME-accredited fellowships in Molecular Genetic Pathology, so it is presumed that they may have sufficient resources to support training in the LGG fellowship. Since this is more of a merging of two currently-approved ABMGG primary specialties, rather than creation of an entirely new one, we anticipate that the training programs will focus on merging of existing resources. The ABMGG and American College of Medical Genetics and Genomics (ACMG) have had meetings in anticipation of developing new educational materials for those seeking certification and maintaining certification for the LGG specialty.

6. Please provide responses to (a) through (d) below regarding the duration and curriculum of existing programs:

a. The goals and objectives of the existing programs:

As described earlier, nearly all the existing programs train in both cytogenetics and molecular genetics. The proposed specialty will combine the goals and objectives of those two programs in an integrated and efficient fashion. They include these specific goals and objectives for the current specialties: Cytogenetics and genomics – train individuals in the methodologies of tissue culture, microscopy, microarray analysis, and fluorescence in situ hybridization, and to identify chromosomal imbalances, understand risks of transmitting those imbalances, as well as understand the incidence and clinical significance in (germline or constitutional) prenatal, postnatal as well as oncologic specimens. Molecular genetics and genomics – train individuals in the methodologies of dideoxy sequencing, Southern blot, MLPA, qPCR, genotyping, next-generation sequencing, and microarray analysis, and to identify sequence and gene-level deletions or duplications, understand the risks of transmitting those mutations, and their incidence in prenatal and postnatal specimen. Currently certification in either CGG or MGG requires 24 months full-time training in an accredited specialty training programs that encompass the defined learning objectives. If an individual expects to become certified in an additional primary specialty, it would require an additional 12 months of full-time clinical laboratory training in that specialty. The LGG training program requires 24 months full-time training, with no months allotted for elective/research time (six of the 36 months are allowed if doing the two current specialties). In summary, the merged LGG certification will require 24 months full-time, clinical training in an accredited program.

NOTE: Attached as Appendix 1 to this application is a document entitled “Learning Guide for Laboratory Genetics and Genomics.” The document was developed by the Board and will help summarize the responses to section 6.

b. The expected competencies that will distinguish this specialist from other specialists in the areas of cognitive knowledge, clinical and interpersonal skills, professional attitudes and practical experience:

The expected competencies that will distinguish this specialist from other specialists in the areas of cognitive knowledge, clinical and interpersonal skills, professional attitudes and practical experience: Cognitive Knowledge: In the area of cognitive knowledge, a diplomate trained in Laboratory Genetics and Genomics (LGG) will be able to issue more thorough and comprehensive results leading to diagnostic and prognostic interpretations, provide a deeper interpretation of test results within the context of a patient’s clinical history, and facilitate improved communication and explanation of these results to providers. Clinical and Interpersonal Skills: Individuals certified in LGG will bring a unique set of clinical skills to the laboratory analysis of patients with presumed genetic or genomic disorders. Notable examples would include an individual who understands the significance of a SNP-based microarray showing long continuous stretches of homozygosity (LCSH) for chromosome 15 in a hypotonic newborn, but who also recognizes when there is a need for additional molecular testing to evaluate for uniparental disomy or for DNA mutation analysis. A critical need fulfilled by these individuals would be that of integrating the relevant genetic and genomic results into a single laboratory report. LGG-certified individuals will be uniquely poised to discuss the relevance of each component of testing performed. In contrast, and with the above example, currently a single patient’s samples may be sent to different labs, from which a molecular geneticist will communicate sequencing results and a cytogeneticist will discuss the significance of absence of heterozygosity (AOH) or LCSH. Such a piecemeal scenario often leaves the healthcare team with knowledge gaps in terms of appropriate next best steps in the care of their patients. Professional Attitudes: An LGG-certified professional would instill confidence in medical colleagues when communicating results and discussing benefits and limitations of testing platforms and test results, and can also guide appropriate additional testing when necessary. Practical Experience: Individuals certified in LGG will have primary specialty training as well as daily practice experience across both molecular and cytogenetic specialties and therefore will be uniquely poised to integrate test results and interpretations that cross the current perceived divide.

c. The scope of practice:

The proposed specialty is not intended to define a new scope of practice but rather a coalescing of the scopes of practice of CGG and MGG. Individuals certified in LGG will be uniquely trained to understand both cytogenetic and molecular-based platforms for constitutional/germline genetic and genomic disorders but will also continue to acquire expertise in the area of oncologic genetics and genomics. LGG fellowships will focus specifically on necessary integration of clinical cytogenetics by providing a chromosomal view of the genome to complement and enhance any molecular-based assay interpretation. The integrated LGG specialty will differ from molecular genetic pathology (MGP), which includes primarily testing in the areas of oncologic and infectious disease. LGG-certified individuals will continue to work in collaboration with physicians and other members of the health care team to contribute to diagnoses, prognoses and clinical management and also to provide mechanistic understanding of genetic factors of disease as well as facilitate genetic counseling as appropriate. In recent years, there has been an increase in diplomates becoming certified in both CGG and MGG. Data from the ACMG Professional Survey, last completed in 2013, also shows that more ABMGG diplomates are working in combined laboratories, supporting the vision of the ABMGG to merge these specialties into one. This is noted in the breakdown of diplomates responding the aforementioned Survey, which shows the increase in respondents over the last several years who are dual boarded in CGG and MGG and who direct combined laboratories (NOTE: Please see Appendix 2 for graphic representation of these survey responses).

7. Please provide a projection and the methodology used for the projection of the annual cost of the required special training:

Rather than this being the creation of a truly novel specialty, this is a focused merger of two existing ABMGG specialties, driven by advances in diagnostic technology that bring cytogenetics and molecular genetics together. As noted previously in the application, the ABMGG has seen a decline in individuals who are seeking certification in cytogenetics alone and an increase in the number that are seeking dual certification in cytogenetics and molecular genetics. The current required training period for cytogenetics and genomics or molecular genetics and genomics alone is 24 months and presently those seeking certification in both specialties must do 36 months of training. We are proposing that in the merging of these two specialties that we will achieve efficiencies that will lead to a reduction in training time to 24 months. This will actually reduce the cost of the training by approximately a third.

a. As the sponsoring Member Board, do you have, or access to, the resources to conduct a regular certification and MOC program in this specialty?

Yes; we currently administer certification examinations as well as MOC programs for both CGG and MGG. We have an established, large bank of questions for both certification and MOC examinations that are currently administered through a contract with the National Board of Medical Examiners (NBME). Therefore, creation of a new certification examination and MOC program for LGG will not require any significant increase in resources for the ABMGG. In fact, once the transition occurs, the Board will be administering one fewer primary specialty certification examination and one less MOC specialty program.

b. Do you plan to ask for ACGME accreditation for this new program?

Presently the ACGME does not offer accreditation for programs that may enroll individuals with a PhD degree (i.e. without MD, DO, or similar medical degree). We recently have been made aware of a potential pathway for ACGME to accredit these programs and we may discuss this with that organization in the future, but at present the ABMGG will continue to accredit programs (see 7c).

c. If these programs are not accredited by the ACGME, please document the accrediting body for this program and whether you have the resources to review these programs in a fashion comparable to ACGME.

The ABMGG currently accredits programs in Clinical Molecular Genetics and Genomics, Clinical Cytogenetics and Genomics and Clinical Biochemical Genetics. Sponsoring institutions may seek initial accreditation from the ABMGG as outlined on our website (www.abmgg.org). After initial accreditation, sponsoring institutions must submit data to ABMGG annually through our online portal (http://www.abmgg.org/pages/program_annual.shtml). This annual data is reviewed by the Accreditation Committee of the ABMGG to ensure that the program remains in good standing. Within two years of initial accreditation and then at least every 5 years afterward, a site visit to the sponsoring institution occurs to monitor the program and document and evaluate the training process at the institution and to assure that all requirements are being implemented and in place. Ad hoc site visits are considered by the accreditation committee as needed. The ABMGG has both adequate financial resources as well as manpower resources to conduct the accreditation o the laboratory training programs. The ABMGG also has a long track record of accrediting programs. The quality of the accreditation process through ABMGG is therefore comparable to the ACGME.

8. Please outline the qualifications required of applicants for certification in the proposed new or modified subspecialty area, as it pertains to the following:

a. Possession of an appropriate medical degree or its equivalent:

The credentialing qualification for applicants for LGG will be identical to those currently in place for all the ABMGG laboratory specialties. A doctoral level degree (either an MD or its equivalent or a PhD) is required.

b. Completion of specified education and training or experience in the specialty field:

All applicants for certification will be required to have successfully completed an accredited training program in LGG as well as fulfill all the other general requirements for credentialing as with all other applicants to our specialty certification examinations. In addition, applicants who have completed accredited training programs in both CGG and MGG will be eligible to apply for this merged specialty examination. The ABMGG may consider, for the first two examination cycle, a “by experience” pathway for those diplomates already certified in either CGG or MGG who document significant expertise and practice in LGG. A logbook of 150 clinical cases over the last two years showing active involvement would be required.

i. Will diplomates from other ABMS Member Boards be allowed to apply for this specialty certificate?

Yes NoIf "yes," but only specific ABMS Member Board diplomates would be allowed to apply for this specialty certificate, please list those Member Boards:

N/A

If "yes," would you require diplomates to maintain their primary certificate? Yes No

c. Additional qualifications:

The applicant must have completed an ABMGG-accredited training program in LGG.

9. Please describe how candidates for certification in the proposed new or modified specialty area will be evaluated. In your response, include a description of the method(s) of evaluation (e.g., written, oral, simulation) and the rationale behind the method(s) used in the evaluation process:

A comprehensive written examination, comparable to those given for the current specialties, will be offered. We do not anticipate any change in this comprehensive method of testing. The content will cover those topics included on the current CGG and MGG examinations. As with all the ABMGG certification exams, all candidates will take a general genetics and genomics examination (all specialty candidates must pass this component) and the LGG specialty examination. The item format, exam statistical analyses, and review will be identical to what is used now.

10. For (a) through (d) below, please project the need for and the effect of the proposed new or modified specialty certification on the existing patterns of specialty practice. Please indicate how you arrived at your response.

a. How the Member Board will evaluate the impact of the proposed new or modified specialty certificate:

i. On its own primary and subspecialty training and practice:

We do not envision any significant impact on the primary or subspecialty training or practice. Those currently

certified in either clinical cytogenetics and genomics or clinical molecular genetics and genomics alone will continue to be able to participate in MOC and to be employed in their fields. As noted previously, many individuals are already dually certified. It is important to note that techniques and technologies employed in the diagnosis of many disorders increasingly are moving cytogenetics and molecular genetics closer together. As an example, the diagnosis of genomic copy number variants and aneuploidies in cancer and congenital disorders increasing employs large scale single nucleotide polymorphism (SNP) arrays and this technology that examines variations at a single nucleotide base would typically be thought of as a “molecular” technique. Conversely, some laboratories now identify copy number variants, segmental aneusomies and aneuploidies through clinical whole exome sequencing and in this case clinical molecular genetics practitioners are using a “molecular” technique to diagnose something that was historically thought of as being in the bailiwick of a clinical cytogeneticist. The ABMGG will monitor the number of individuals enrolling in and completing fellowships as well as the number applying for certification and board certification examination scores and pass rates for any impact.

ii. On the primary training and practice of other Member Boards:

We do not anticipate any effect on the training and practice of other ABMS member boards. Currently there is no other member board that offers certification in clinical cytogenetics or a related field. The American Board of Pathology offers subspecialty certification in Molecular Genetic Pathology (MGP) to MDs with primary certificates in Pathology or Clinical Genetics. This is a one-year subspecialty training requirement. It is acknowledged that there is some overlap between MGG and MGP. Of the two specialties, MGP is the newer one and MGP programs are currently accredited by a special RRC that is comprised of members of the Medical Genetics and Genomics RRC and Pathology RRC. Additionally, the certification examination is developed jointly by the American Board of Pathology and the ABMGG. The training and certification examination for MGP is more centered on molecular diagnostic techniques and diseases more aligned with most hospital laboratories as is evidenced by program requirements more focused on infectious diseases (molecular microbiology), identity testing, histocompatibility and hematopathology, and some inherited conditions. In contrast, the logbook that applicants must submit to the ABMGG to apply to take the certification examination does not mention or require infectious diseases, histocompatibility or hematopathology nor are these mentioned in the learning guide published by the ABMGG.

b. The value of the proposed new or modified specialty certification on practice, both existing and long-term (in health care, value is typically defined as quality divided by cost), specifically:

i. Access to care (please include your rationale):

A combined program that provides cytogenetics and molecular genetics training as well as bioinformatics training will equip those certified in LGG with the required knowledge and expertise to appropriately and fully interpret data from whole exome or whole genome screening methods, which are becoming standard first-tier tests in genetic testing. Currently, separation of cytogenetic and molecular genetic testing requires physicians to send multiple samples to different laboratories, collect reports from these different sites, and tolerate disconnected interpretations of genomic data. With combined training, laboratory professionals are able to interpret both cytogenetic and molecular data and therefore improve access to their services, will not require multiple sample submissions, and will provide a combined analysis that explains both cytogenetic and molecular genetic information in appropriate context in a single report. This results in efficient and ideal laboratory genomic medicine. It would reduce cost, enable more centralized testing, and provide more comprehensive patient care. New York state law already offers a precedent: it currently requires both a cytogeneticist and a molecular geneticist to interpret and sign whole genome microarray reports.

ii. Quality and coordination of care (please include your rationale):

The shorter duration of an LGG fellowship will both decrease the overall cost of training such individuals and produce diplomates who are better able to meet the high complexity clinical testing needs. LGG-trained geneticists will also be well-situated to integrate results and interpretations that address clinical utility and provide the physician comprehensive results to use in clinical context.

iii. Benefits to the public (please include your rationale):

Creation of the LGG specialty and the resulting integration of test results will lead to improved test interpretation, thereby having a positive impact on clinical management decisions. This in turn will contribute to more efficient healthcare spending and also may help reduce unnecessary testing. As has already been mentioned in this application, New York state already requires that microarray results be jointly interpreted by individuals who have been trained in cytogenetic and molecular specialties, and this action reflects a growing appreciation of the need for well-trained laboratory geneticists in understanding and communicating results of high complexity genetic testing.

c. Please explain the effects of the proposed new or modified specialty certification on:

i. Immediate costs and their relationship to the probable benefits (please indicate your methodology):

The immediate costs of merging these primary specialties will not be significant because the necessary training programs already exist and need only to be integrated at each appropriately accredited site. We anticipate, or at least hope, that an overall cost savings to the healthcare system and to patients should result as comprehensive testing can be both designed and implemented at an institutional level, thereby making the system more efficient and lowering costs. An immediate benefit of this process will be the ability to issue a single, integrated genetics/genomics report interpreted by appropriately trained individuals and this, in turn, will increase efficiencies. This will allow LGG-certified individuals to provide more appropriate and thorough support to referring physicians through discussion of the laboratory results and potential clinical implications of integrated laboratory reporting. Currently, laboratory tests performed for one patient may occur in multiple laboratories. An LGG certified individual would appreciate and understand data that span both cytogenetics and molecular genetics and be qualified to issue a single, integrated report. Such a report would: provide results from complementary testing platforms; issue both broad and focused interpretation of results in the context of clinical history, and; summarize recommendations for the healthcare team. In the absence of such integration, this burden currently falls to the primary provider(s), who are not typically comfortable fulfilling this role.

ii. Long-term costs and their relationship to the probable benefits (please indicate your methodology):

We do not anticipate additional costs from merging the two current specialties into one comprehensive specialty. Any long term costs of this merged specialty will be shared by systems development throughout health care as well as direct payments to physicians, hospitals, clinics, and others. These costs will be greatly offset by savings noted in this application. Because the ABMGG laboratory specialties are not procedure-driven and will be accessible across medical specialties, and because genetic and genomic testing often identifies a diagnosis or prognosis sometimes not otherwise realized, significant benefits will result. Specialty certification will improve the availability and quality of patient care, which will continue to reduce significant health care costs.

d. Please explain the effects if this specialty certification is not approved:

Laboratory Genetics and Genomics is a combined/merged specialty of two current specialties – CGG and MGG. If this new specialty is not approved, the medical community risks leaving in place a fragmented genomic testing environment when technologies have advanced to enable unified analysis of cytogenetic and molecular information. This can lead to missed or conflicting clinical diagnoses by physicians due to lack of access to appropriately contextualized genomic information with cytogenetic and molecular genetic information presented together. In addition, the number of individuals training only in clinical cytogenetics and genomics is decreasing, likely leading to reduced access to cytogenetic testing in the future and a consequent decline in the quality of genomic healthcare for patients. Lastly, interpretation of cytogenetic data by molecular geneticists not trained in that area or vice versa poses a risk to our healthcare system and to patients because those professionals will lack comprehensive understanding of necessary concepts to deliver appropriately contextualized and comprehensive genomic information. To avoid this risk, as an important example and likely a harbinger of a practice that may become more widespread, New York State law currently requires both a cytogeneticist and a molecular geneticist to sign whole genome microarray reports and will likely impose a similar rule if cytogenetic information in the near future is inferred only from whole exome sequencing data.

11. Please indicate how the proposed new or modified specialty will be reassessed periodically (e.g., every five years) to assure that the area of clinical practice remains a viable area of certification:

The proposed LGG specialty is the merger of two, longstanding specialties that have clearly demonstrated long-term viability over many years. The numbers of accredited training programs and new trainees are stable or have grown and we anticipate no change. In addition, new technologies and tools for a variety of testing modalities and clinical applications continue to expand which will assure that LGG continues to remain a viable area of certification.

12. Please list key external public stakeholders that COCERT may solicit for possible public comment on the proposed new or modified specialty area:

NOTE: When submitting this application, please attach the following items:

Copy of proposed application form for the candidates for certification

A written statement indicating concurrence or specific grounds for objection from each Primary and Conjoint Board having expressed related interests in certifying in the same field

Written comments on the proposed new or modified specialty area from at least two (2) external public stakeholders

A copy of the proposed certificate for ABMS records

COCERT Application - Laboratory Genetics and Genomics Appendix 1

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The following is a summary learning guide for LGG compiled by the Board, which helps to summarize the responses to section 6.

American Board of Medical Genetics and Genomics Learning Guide for Laboratory Genetics and Genomics

July 2015 INTRODUCTION: These learning guides have been developed by the ABMGG to assist training program directors and trainees as they design, implement, monitor and evaluate the educational content of their ABMGG accredited training programs. The format of these learning guides reflects the common areas of knowledge and training that have been developed by the medical profession across the training spectra and that are often referred to as the “Six Competencies”. The ABMGG has taken these areas of knowledge and experience and translated them into more specific content areas for ABMGG accredited programs. These learning guides are not presumed to be inclusive or exclusive. Thus you will find that they mirror many other guiding principle documents from within the genetics community. Similarly, while they attempt to cover as many specific areas of training as possible, they cannot be viewed as the only areas of knowledge and expertise that are required to become a successful medical genetics professional. They are, as indicated, learning guides; and are not rules or testing outlines. These guides are offered to the medical genetics educational community as one source of information concerning knowledge areas that may be useful in developing and evaluating the educational content of training programs.

Domain Objectives Skills

1. Patient care Pre-analytic laboratory skills

Identify appropriate specimens for study, and methods of collection, preservation, and transport

Select appropriate containers, anticoagulants, collection media, antibiotics, and preservatives for validated specimen type. Identify factors important for the transport of specimens, such as overnight delivery, transport media and containers, recommended temperatures. Transport/ship specimens off-site using packaging that meets OSHA guidelines. Be aware of appropriate specimen and handling requirements.

Assess acceptability of specimen for study

Check for appropriate labeling of specimen and requisition. Evaluate suitability of specimen for requested study, both for tissue type and amount obtained. Judge quality of specimen. Assess for presence of interfering substances: presence of blood in amniotic fluid, blood clots or hemolysis in blood samples, syringe number and presence of spicules in bone marrow, quality of bone core, FFPE fixation methods and thickness of unstained slides for FISH studies, quality of DNA from paraffin-


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embedded blocks, DNA with suboptimal A260/A280 ratios, fragmented DNA, etc. Describe methods for possible recovery of poor samples. Notify appropriate individuals of unsatisfactory samples and document such notification.

Accession specimen Assign unique laboratory accession number to specimen. Record related data. Including patient’s name and all required and pertinent information including identification numbers, date of birth, sex, clinical history, indication for study, referring physician. Record accurate and complete information concerning specimen including type of tissue, amount, appearance, collection date and time, anticoagulant etc. Record priority status of specimen and identify as appropriate. Record notes of any special test requests, particularly those requiring transport of samples to other laboratories. Record chromosomal region of interest in high-resolution chromosomal studies or gene/sequence of interest for molecular studies.

Tracking of specimen Follow protocols to ensure proper identification of patient materials through the complete process, from accession to final report. Be able to track specimen through all aspects of the testing process.

Appropriate documentation Maintain necessary records and laboratory database, in logbooks or computers, as appropriate.

Appropriate culture techniques for submitted specimens

Use of aseptic techniques Use Universal Precautions for potential against potential exposure to infectious agents (e.g., protective clothing, gloves and masks, containers for sample delivery and waste disposal, biological safety cabinets). Use and document methods to detect, identify, control, and eliminate microbial or chemical contamination. Practice measures that prevent cross-contamination between samples.

Prepare appropriate media for specimens, giving consideration to the clinical indication for the study.

Choose appropriate medium additives such as sera, antibiotics, buffers, mitogens, and growth factors. Select appropriate methods of preparation and storage of media to maintain pH, sterility, and ability to support growth.

Employ appropriate culture techniques for specimen.

Select culture equipment and vessels for closed or open culture system. Select culture technique for specimen taking into account type of tissue, methods


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of initiation, type of culture, and purpose for study. Appraise the effect of cell density on rate of growth and adjust appropriately (e g., cell count of leukemic specimens). Monitor and document the effectiveness of all solutions used in the procedures prior to use on diagnostic material. Record complete information for culture of specimen, including identification of technologist, lot numbers of media, sera, and other reagents, incubator used, and mitogen, if used.

Monitor cell growth and control variables.

Employ measures that will maintain optimal cell growth (e.g., feeding and spinning of cultures to correct for depleted medium). Evaluate status of cultures using assessment of growth and mitotic activity, pH of medium, and turbidity. Identify and document probable causes of poor growth and culture failure, such as inadequate specimens, or equipment failure, and corrective actions taken. Report findings of culture failure or growth inadequate for analysis to laboratory personnel, and request new sample, if appropriate.

Principles and techniques for harvesting specimens or cell cultures

Determine optimal time sequence and method for harvest (manual or robotic).

Apply knowledge of cell cycle for various cell types and culture conditions (e.g., PHA stimulated lymphocytes, unstimulated leukemic cells, synchronized cultures, chorionic villus or amniotic fluid cells, fibroblast or solid tumor cultures) to determine time for harvest.

Use appropriate harvest procedures for specimen or culture.

Understand the use synchronizing or intercalating agents, such as amethopterin, fluorodeoxyuridine, bromine deoxyuridine, ethidium bromide, or actinomycin D, at appropriate concentration, temperature, and duration. Use spindle fiber inhibitor (e.g., Colcemid, Velban) at correct concentration, temperature, and duration. Use recommended procedure for removing cells from culture vessels. Use appropriate hypotonic solution (KCl or sodium citrate), at correct concentration, temperature, and duration. Use cell fixative (acetic acid/methanol) at correct concentration, temperature, and duration. Control mechanical damage to chromosomes by proper mixing, shaking, pipetting, centrifuging, or other handling of the cells.


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Record complete information for harvest of specimen including date, addition of spindle fiber inhibitor, intercalating or synchronizing agents, conditions used for harvest, and name of technologist processing the samples.

Prepare slides with analyzable metaphases

Select method of slide preparation that will produce high quality metaphases with optimum spreading (e.g., control variables such as wet or dry slides, air flow, humidity level and temperature during air drying to regulate slide drying rate.) Employ techniques that control concentration and distribution of cellular and other debris on slides. Evaluate quality of slides with phase contrast microscope and adjust variables as necessary. Employ techniques that control the aging of slides to produce optimal banding conditions (e.g., storing at various temperatures, such as 37°C, 60°C, 90°C, for various times, such as 20 min to 2 hours, or overnight; UV exposure or microwave). Use slide storage methods that best maintain chromosome quality for banding and staining procedures, with protection from humidity, light, chemicals, or mechanical damage.

Principles and techniques of chromosome banding and staining

Understand how to select banding and staining methods that permit identification of each chromosome pair, at an appropriate band level

Use G-banding pretreatment and staining methods, utilizing trypsin, 2XSSC, urea, or other chemicals. Understand the results for other specialized staining procedures when needed (e g., DAPl/Distamycin A, sister chromatid exchange, etc.) and recognize the advantages and disadvantages of these methods.

Select mounting materials, hydration/dehydration methods, and destaining techniques when necessary for multiple staining procedures on the same slide.

Understand the appropriate destaining method necessary for re-banding or re-staining of a previously banded/stained slide. For FISH analysis, select the appropriate type of specimen and type of probe for both interphase and metaphase FISH analyses. Perform appropriate slide pretreatment, denaturation, dehydration, hybridization and detection for both directly and indirectly labeled probes for interphase and metaphase FISH analyses on cultured and uncultured cells. Understand the use and interpretation of controls for FISH analysis.

Select slide cleaning and storage


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methods that maintain quality of chromosome preparations for period of time required by regulatory agencies.

Troubleshoot unacceptable or unanalyzable results for all banding/staining procedures.

Maintenance and use of microscopes and computer-generated imaging techniques and equipment

Operate a standard compound microscope, inverted microscope, stereo microscope, and computerized karyotype equipment.

Clean, adjust, focus, and use appropriate illumination systems, eyepieces, objectives, condenser systems and filters, for bright field, fluorescent, and phase contrast microscopes. Operate microscopes and computerized image capture system equipment for optimal resolution of specimen. Demonstrate appropriate use of coverslips and immersion oil. Maintain computer image analysis equipment in optimal working order.

Select methods that produce optimal chromosome images.

Produce electronic images with clarity.

Chromosome analysis

Select suitable metaphases/interphase cells for analysis.

Select metaphases according to morphology, spreading, length, and banding detail. Assess difficulties in microscopic analysis and computer imaging posed by overlapping chromosomes, debris, poor stain, etc.

Perform accurate microscopic counts and analyses of banded and non-banded chromosomes

Analyze chromosomes at the microscope, and identify normal/abnormal karyotype. Document the analysis of separate colonies on amniotic in situ cultures.

Record microscope identification, stage coordinates, and cell analysis data on all cells selected.

Document analysis in an organized manner (e.g., patient information, modal number, sex chromosome constitution, aberrant chromosomes, slide identification and verniers, identification of technologist, and date of work). Use a method that allows rapid retrieval of any cell analyzed, on the same or another microscope, (e g., use of a calibrated microscope stage, microlocator slide, conversion chart).

Prepare accurate karyotypes from computer images.

Organize chromosomes according to a systematic and approved format (e.g., ISCN).

Identify numerical and structural chromosome abnormalities, and

Determine numerical abnormalities of the autosomes and sex chromosomes. Differentiate between the presence of multiple cell lines, and random gain and


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relate their implications (e.g., phenotype and relationship to disease).

loss of chromosomes in slide preparation of specimens and/or controls. Identify constitutional structural abnormalities such as translocations, deletions, inversions, ring chromosomes, isochromosomes, and fragile sites. Identity sporadic structural abnormalities such as chromatid breaks, chromatid exchanges, fragments, and endo-reduplication. Understand how to identify heteromorphic chromosomes with different variable regions, by band number, code letters, size, and banding intensity.

FISH Analysis Select suitable

metaphases/interphase cells for analysis Select appropriate regions of interest from paraffin sections

Select the appropriate type of specimen and type of probe for both interphase and/or metaphase FISH analysis. Determine the appropriate conditions for pretreatment, dehydration, hybridization, washing and counter-staining of FISH slides. Understand procedures for selection of areas for FISH analyses on FFPE slides.

Perform accurate microscopic counts and analyses

Recognize the appropriate metaphases and/or interphase nuclei for FISH analysis. Recognize the appropriate signal(s) and/or signal patterns. Count the appropriate signal(s) and/or signal patterns. Document the detection of signal numbers for specimens and controls. Understand the normal range or cut-off values for each probe/probe combination.

Record microscope identification, stage coordinates, and analysis on selected cells.

Document analysis in an organized manner (e.g., patient information, slide identification and verniers, identification of technologist, and date of work). Use a method that allows rapid retrieval of any cell analyzed, on the same or another microscope, (e g., use of a calibrated microscope stage, microlocator slide, conversion chart).

Prepare correct number of images

Prepare correct number of FISH images as recommended by the ACMGG/CAP guidelines for both metaphase and interphase FISH

Microarray analysis DNA extraction and purity Extract DNA and determine purity and concentration.

Determine the appropriate amount of DNA necessary for microarray analysis, dependent upon platform type.

DNA labeling of target and control DNA

Fluorescently label DNA necessary for microarray analysis. Determine the specific activity and the yield.

Microarray hybridization and Determine the appropriate conditions for microarray hybridization and post-


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washing hybridization washing, dependent upon platform. Scan and analyze the data as per platform. Archive the appropriate data.

Microarray data analysis Use the appropriate software for data analysis, as well as proper use of the appropriate databases (e.g. UCSC Genome Browser, Database for Genomic Variants, DECIPHER, etc.). Explain relationships between microarray and karyotype data Perform relevant follow-up chromosomal studies to correlate with array findings Understand principles of detecting copy number variation and genotyping data from microarrays and next-generation sequencing • Intragenic and large multigenic copy number variants • Homozygosity stretches in the genome indicative of IBD/UPD • Concepts behind array probe design and relationship to data • Use genome browsers to evaluate array designs and hybridization results

Appropriate techniques for nucleic acid isolation from submitted specimens

Use of techniques Use Universal Precautions for protection against real or potential exposure to infectious agents (e.g., protective clothing, gloves and masks, containers for sample delivery and waste disposal, biological safety cabinets). Use and document methods to detect, identify, control and eliminate microbial or chemical contamination. Practice measures that prevent cross-contamination between samples.

Choose appropriate method for DNA/RNA isolation

Isolate DNA/RNA expediently, with consideration to specimen type and test requested Choose appropriate type of solution (e.g., TE, water, etc.) for reconstitution of DNA/RNA Choose appropriate amount of reconstitution solution for test being performed Practice measures that prevent cross-contamination between samples. Monitor automated extraction instruments for carry-over

Determine concentration of DNA/RNA, as appropriate

Options to estimate concentration and determine quality of DNA/RNA include: • spectrophotometry (determine optical density and nucleic acid/protein

ratio of reconstituted DNA/RNA) • fluorometry (estimate DNA concentration)


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Direct visualization by gel electrophoresis Understand probable causes of

poor or failed DNA/RNA isolation Identify, evaluate, and document probable causes of poor or failed DNA/RNA isolation, such as inadequate specimen or reagent failure. Document corrective actions taken.

Storage of DNA/RNA samples appropriately

Employ proper techniques for storage of DNA/RNA samples.

Principles and techniques for polymerase chain reaction (PCR).

Know and understand principles and techniques associated with PCR analysis

Understand the principle of PCR. Determine components and concentrations for particular reaction. Assemble reagents for master mix. Calculate primer dilutions. Optimize conditions for amplification. Troubleshoot failed or non-specific reactions. Utilize appropriate controls.

Know which primers are appropriate for disease/area of concern

Perform or be familiar with the development and design of new primers.

Perform PCR to minimize carry over (false positive results)

Utilize unidirectional workflow. Utilize adequate physical separation of pre- and post-amplification samples to avoid amplicon contamination. Change gloves frequently during processing. Use dedicated pipettes (positive displacement type or with aerosol barrier tips). Manipulations must minimize aerosolization. “No template” controls in which target DNA is omitted (no product is expected) should be included in each run. Monitor liquid handlers to eliminate carry over.

Southern analysis Understand principles and techniques associated with Southern blot

Understand aspects of the Southern blot procedure including • digestion of DNA with appropriate restriction enzymes; • electrophoresis; • denaturation in alkali and transfer DNA to membrane • preparation of probe (radioactive or chemiluminiscent label); • denaturation of probe and hybridization of membrane; • exposure to X-ray film and development of the autoradiograph.

Targeted mutation Understand principles and Understand a variety of methods for direct mutation detection, e.g.,


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analysis techniques associated with direct mutation detection

• restriction fragment length polymorphism analysis; • FRET analysis (Invader); • allele-specific oligonucleotide dot blot hybridization; • allele-specific PCR amplification (ARMS); • Pyrosequencing; • Exon-focused array CGH • Molecular inversion probe • Multiplex ligation-dependent probe amplification (MLPA)

Gene Scanning Understand principles and techniques associated with gene scanning

Observe, perform, or be familiar with methods for gene scanning, e.g., • heteroduplex analysis; • melting curve analysis • MLPA

Sanger (dideoxy) Sequencing

Know and understand principles and techniques associated with dideoxy sequencing of single genes or exons

Be familiar with concepts behind Sanger dideoxy sequencing Perform direct DNA sequencing.

Next-generation sequencing

Know and understand principles and techniques associated with sequencing of gene panels, whole exomes, or whole genomes

Understand the technical details of next-generation sequencing – limitations and advantages of different methods of library preparation and sequencing Understand the challenges, limitations, and advantages between gene panels, exome, whole genome sequencing Understand the assay design process, including selecting capture baits for hybridization or primers for microdroplet PCR Understand the refinement steps of assay design to optimize data generation at difficult genomic regions, e.g., at repetitive sequences or GC-rich sequences Determine components and concentrations for library preparation and sequencing. Optimize conditions for library preparation and sequencing. Troubleshoot failed or non-specific reactions. Utilize appropriate controls. Understand new test validation approaches for NGS-based tests

Quantitative PCR

Know and understand principles and techniques associated with quantitative PCR

Observe, perform or be familiar with the use of quantitative PCR to quantify gene dosage and to assay for mutations and single nucleotide polymorphisms.


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Array Analysis Know and understand principles and techniques associated with microarray analysis

Observe, perform or be familiar with the use of microarrays in the laboratory to identify single nucleotide variants, single-gene intragenic deletions and duplications, or chromosomal copy number variants. Understand principles of genotyping and its applications Understand concepts of array probe design and relationship to data

Identity testing Know and understand principles and techniques associated with identity testing

Perform identity testing using the analysis of polymorphic genetic markers (NOT gene mutations associated with disease), e.g.,

• paternity testing; • forensics; • zygosity; • transplantation; • maternal cell contamination

General laboratory skills, quality control, and quality assurance

Know how to prepare reagents. Prepare reagents at the proper concentration and pH, with proper labeling and dating, using required grades of water and chemicals.

Know how to select, operate, clean, and maintain all laboratory equipment and instruments, as appropriate.

Monitor the need for service or repair on any equipment and report this to appropriate authority. Document usage of gas tanks, and replace as necessary. Record equipment temperatures with reference thermometers, and adjust controls if necessary. Monitor centrifuge speed, using a tachometer and adjust if necessary. Be aware of regulatory requirements for preventative maintenance of equipment and documentation of equipment repairs. Be aware of the need for regular instrument function checks and how this is documented in the laboratory.

Understand principles of sterilization and decontamination procedures

Able to use disinfectants, steam, dry heat, gas, U.V. irradiation, and membrane filtration appropriately.

Understand how to stock laboratory supplies and chemicals.

Maintain adequate stocks of laboratory supplies and chemicals. Employ limits on stock usage imposed by shelf life and expiration dates.

Practice established procedures Employ appropriate cleaning procedures for laboratory glassware and


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for general laboratory safety. instruments. Use Universal Precautions as established by Centers for Disease Control (CDC) and individual state or local governments. Use appropriate procedures for laboratory emergencies (e.g., fire, accidental injury, natural disaster, chemical spill, or power failure). Use correct procedures for storage, handling, and disposal of different types of materials and waste: biological and chemical, volatile or stable; radioactive; sharps and glass.

Maintain a system to ensure laboratory quality control in all areas, to comply with all regulatory requirements.

Maintain a system to (1) ensure accuracy of chromosomal results, including appropriate documentation, throughout all steps of laboratory procedures; (2) ensure accuracy of molecular tests, including appropriate documentation, throughout all steps of laboratory procedures (3) ensure confidentiality and security of patient records; (4) appropriately label, store, and monitor shelf life, sterility, and quality of all media, sera, reagents and chemicals. Maintain an easily accessible collection of current Material Safety Data Sheets (MSDS) for all chemicals used in the laboratory procedures. Maintain a system of records for equipment and instruments (serial numbers, date of purchase, maintenance checks, gauge readings, dates and type of service or repair). Practice the techniques, procedures and policies used in the laboratory, as documented in the laboratory manual. Assist in reviews and revising the laboratory manual. Participate in laboratory proficiency testing, as appropriate.

Bioinformatics Software Use and understand software packages for clinical lab processing, data analysis and storage, and for report writing. • Understand implications of using electronic record keeping with respect to health information. • Understand the informatics processes that connect sample requisition to wet lab processes, data analysis, report writing, and transmission of final reports to referring physicians • Understand processes to collect information from multiple individuals in the process between sample accession to final report.

Variant calling Learn to use software for next-generation sequencing for read alignment, variant


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calling, and confirmations • Genome sequence alignment software (e.g., BWA) • Variant calling algorithms (e.g., GATK) • Identifying artifacts and trouble spots in genome sequence data • Visualizing single nucleotide and copy number variation • Basic biostatistical analysis of sequencing data (depth of coverage, read quality, Q scores, mapping quality, etc) • Analyzing and integrating data from orthogonal confirmation methods • Understand the utility of and how to use in silico prediction algorithms (e.g., Polyphen, SIFT, splice detectors)

Interpretation of genomic sequence data

Observe and understand how to use: • Genome browsers (UCSC, IGV, ENSEMBL) • Human genome variation databases (e,g,, ClinVar, 1000Genomes, ESP) • Variant analysis software, if available (custom software or vendor software) • in silico algorithms for prediction of effects of missense changes (PolyPhen, GERP, SIFT, Alamut, etc) Understand basic biostatistical concepts – case-control studies, odds ratios, use of different statistical measurements, appreciating outcomes of population studies

Exome analysis Perform singleton and trio analyses of exome sequence data Apply principles of homozygosity mapping and search for recessive disease mutations Apply principles of using phenotype information to isolate gene lists for analysis Apply modeling inheritance modes (dominant, recessive, X-linked) based on pedigree of tested individual and create priority gene lists for analysis Create and use virtual gene panels for analysis based on disease phenotype information Understand limitations of sequence depth coverage and implications for diagnostic testing Use workflow for analyzing and reporting incidental findings

Post-analytic molecular laboratory skills

Summarize the results and report to the appropriate authority

Recognize and avoid hazards implied in oral reporting of results. Draft a neat, accurate report using standard nomenclature established by the current ISCN, summarizing the findings in understandable text and incorporating


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the patient identification, and all relevant clinical and laboratory data; forward to the appropriate individual for review and signature. Document oral and preliminary reports on final written report.

Understand additional studies needed to make a diagnosis

Report the need for additional studies to complete the diagnosis: repeat the culture, perform additional staining techniques, analyze other tissues, request family studies, FISH, microarray, DNA extraction from a new sample, confirmation by other molecular method, biochemical studies, etc.

Interpretation of results Correctly interpret results of all laboratory assays to determine normal/affected/carrier status. Correlate results with other laboratory results and/or clinical information to develop an appropriate interpretation of the laboratory results.

Report Prepare and generate reports (including pre-written and de novo results and interpretations) incorporating all relevant clinical and laboratory data. Understand how bioinformatics pipelines can be used to prepare primary reports and issue amended reports Use nomenclature as standardized by the Human Genome Variation Society (HGVS) to describe molecular results

Communication Communicate results verbally to ordering physician, his or her designee, or genetic counselor as appropriate, following HIPAA guidelines.

2. Genetics knowledge General principles of biology and genetics

Understand principles of general biology and genetics that relate to cytogenetics.

Describe cell structure and their function. Summarize the stages of the cell cycle, and of mitosis and meiosis (both spermatogenesis and oogenesis). Describe DNA structure (base sequence, complementarity, etc.), and function (genetic code, replication, transcription and translation, and mutations) chromosome ultrastructure: telomeres, centromeres, nucleosomes, histones, loop domains, scaffolding, DNA packing, etc. Review basic embryology and the origin of various tissues: blood, skin, CVS, and amniotic fluid. Describe basic principles of inheritance (dominant or recessive, autosomal or sex linked, multifactorial, polygenic, Lyon hypothesis, imprinting, etc.). Describe mutagenicity and principles of genetic toxicology. Understand genome structure – gene structure, low-copy and high-copy repeat


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sequences, chromosomal structure, unstable regions, conserved regions Understand principles of clinical

cytogenetics. Describe etiology of chromosomal abnormalities such as anaphase lag, non-disjunction, dispermy, breakage and repair, uniparental disomy, and the influence of these processes of maternal age effect, clastogens, inherited breakage syndromes and imprinting. Discuss basic principles of genetic counseling including pedigree analysis and risk calculations for inherited conditions. Discuss basic principles of cancer cytogenetics including hematopoiesis, clonal evolution, and findings during remission and relapse. Correlate molecular genetics results with cytogenetics for prenatal diagnosis, family studies, and cancer cytogenetics. Be familiar with clinical features of common constitutional and acquired cytogenetic disorders including aneuploidies, microdeletion and breakage syndromes, hematologic neoplasms and solid tumors. Understand intragenic and large multigenic copy number variants Understand the mechanism for formation and implications of homozygosity stretches in the genome indicative of IBD/UPD

Understand principles of general biology and genetics that relate to molecular genetics

Understand DNA structure (base sequence, pairing, replication and packaging into chromosomes). Explain transcription, splicing, translation, and variation of gene expression between tissues. Explain genomic organization and gene structure. Understand core technologies for allele discrimination and mutation detection.

Understand principles of molecular genetics

Explain mode of inheritance at level of organism (dominant, co-dominant, recessive, autosomal, sex-linked, multifactorial, polygenic, inheritance of imprinted genes). Explain action of gene at cellular level (dominant-negative, recessive). Describe different classes of mutations (e.g. missense, nonsense, deletion, insertion, splice-site, triplet repeat expansion). Explain gene expression at cellular level (dominant, dominant-negative, or negative). Discuss basic principles of genetic counseling including pedigree analysis. Perform Bayesian risk analysis.


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Describe risk factors for mutations (advanced maternal age and nondisjunction, advanced paternal age and new autosomal dominant mutations, mutagens and carcinogens). Correlate molecular genetics results with cytogenetic results for prenatal diagnosis, family studies, and cancer diagnostics or cancer risk assessment and any other preanalytic clinical information.

3. Interpersonal and communication skills Inheritance/risk counseling

Understands concepts of heritability, inheritance patterns, variability, heterogeneity, penetrance and the epidemiology/natural history of a condition.

Transmit pertinent information in a comprehensible way. Explain genetics concepts and identify family members at risk.

Professional communication

Know how to communicate with colleagues

Maintain comprehensive, timely and legible medical records. Communicate appropriate information to health professionals one-on-one or in groups.

Exhibit appropriate ethnical and professional standards at all times

Demonstrate an attitude of responsibility and respect to the patient, a respectful and cooperative attitude toward professional colleagues and an honest, forthright manner in carrying out professional tasks.

Know how to teach and supervise Educate, mentor, and assess progress and skills, and provide appropriate feedback and appraisal.

4. Practice-based learning and Improvement Standards of care Knowledge of relevant practice

guidelines or consensus statements

Compare own laboratory practices and outcomes to accepted practice/guidelines and national or peer-reviewed data; reflects on areas of uncertainty to identify improvement needs.

Ongoing learning Know how to keep up-to-date in common clinical cytogenetics topics.

Seek feedback from others; can research topics when needed; critiques research evidence for applicability to laboratory practice; uses bioinformatics resources. Is receptive to feedback. Participate in ABMGG Expanded Maintenance of Certification.

Quality improvement

Know quality metrics Change practice behaviors in response to feedback from others and review of own practice; apply new skills or knowledge to laboratory service. Exhibit willingness to change and to adapt.

5. Professionalism


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Responsibility Understand the responsibility to the patient/family

Complete the tasks required to provide laboratory services effectively in a careful and thorough manner.

Practices within ability

Recognize limits of his/her abilities Seek consultation when appropriate. Exercise authority accorded by position and/or experience. Recognize cognitive, legal and ethical limitations of credentials.

Patient diversity Recognize differences (cultural, educational, etc)

Recognize each patient’s unique needs and characteristics. Provide equitable services regardless of patient culture or socioeconomic status. Is respectful and sensitive to issues related to patient culture, age, gender and disabilities.

Integrity and ethical behavior

Recognize ethical dilemmas and potential conflicts of interest. Knowledgeable about the elements of informed consent, privacy, confidentiality, duty to warn, and is HIPAA compliant.

Take responsibility for actions; admits mistakes; tries to address ethical dilemmas and conflicts of interest. Demonstrate a commitment to ethical principles pertaining to (1) patient privacy and autonomy, (2) the provision or withholding of test results, (3) confidentiality of patient information, (4) informed consent, (5) conflict of interest, and (6) business practices that are in conflict with stated principles of professionalism.

Health professional relationships

Know how to interact with health professionals

Courteous and respectful when relating with peers and referring healthcare providers.

Leadership Know teamwork and leadership skills. Knows how to teach and supervise.

Provide direction to staff. Educates and mentors, can assess progress and skills and provide appropriate feedback and appraisal.

6. Systems-based practice Service coordination

Know how to provide comprehensive and integrated service

Coordinate services with other providers; provides timely service.

Evidence-based medicine

Knowledge of evidence-based guidelines and appropriate billing

Determine cost and cost components of tests and understand reimbursement issues; provide cost-conscious services; consider costs & benefits of test; follows accepted laboratory guidelines; uses appropriate billing codes.

Evidence-based medicine

Understand research principles Critically read and interpret scientific publications. Be aware of policy implications.

Health services Understand system resource utilization; understand different healthcare delivery systems and

Interface with laboratory information systems, electronic health records, and billing systems.


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medical practices. Health services Information access Conduct literature review and database searches.

Identify resources for the patient/family and referring healthcare provider.


Figure 1: Data compiled from the American College of Medical Genetics & Genomics (ACMG) biennial survey. Of the respondents certified by the ABMGG to run a diagnostic laboratory, there is an increase in those with dual certification in cytogenetics & molecular genetics.

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Data compiled from the ACMG biennial survey showing the type of diagnostic laboratories where ACMG fellows are employed. Note the increase in ACMG fellows working in laboratories that do both cytogenetics & molecular genetics.

Respondents by Type of Lab Directed

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Mol

Cyto+Mol

December 2, 2015 To Whom it May Concern: I am writing to express my full support for the Laboratory Genetics & Genomics specialty training proposed by the American Board of Medical Genetics and Genomics (ABMGG). As a physician with over 20 years of experience in the field of prenatal diagnosis and reproductive genetics, I am actively involved with prenatal and reproductive genetic counseling on a daily basis, including counseling for genomic testing results. I therefore understand all too well how comprehensive and holistic interpretations of the genetic test results are critical to ensure accurate diagnosis and management of patients. Moreover, this approach will lead to a more unified diagnostic health system by bringing together heretofore separate disciplines. For patients with prenatally identified fetal abnormalities or a strong family history of such findings, accurate diagnosis often requires testing that looks at both DNA sequence changes as well as changes in chromosome copy number. Historically, this required two or more separate tests and interpretations by two different laboratorians. As a clinician this would often require ordering two or more separate tests from different laboratories and then receive multiple interpretations and reports that have to clinically reinterpreted and integrated, with inherent limitations of not having the primary laboratory data. By merging cytogenetics and molecular genetics into a single specialty of Laboratory Genetics & Genomics, this will ultimately allow a clinician’s to obtain a more informed and comprehensive diagnosis for a patient with a single test and interpretation, rather than multiple individual tests. This will undoubtedly serve to improve healthcare delivery and patient care and significantly reduce physician and healthcare administrative burdens and cost. It is therefore critical that genetics laboratory directors be able to interpret both “cytogenetic” and “molecular” test results to ensure that clinicians and patients receive an accurate diagnosis while reducing the burden on the patient and healthcare system. Sincerely,

Ignatia Van den Veyver, M.D Professor, Department of Obstetrics & Gynecology and Department of Molecular & Human Genetics Baylor College of Medicine

IGNATIA B. VAN DEN VEYVER, M.D. Professor Department of Obstetrics & Gynecology and Department of Molecular & Human Genetics Director for Clinical Prenatal Genetics Jan and Dan Duncan Neurological Research Institute 1250 Moursund Street, NRI 1025.14 Houston, Texas 77030 832-824-8125 Office 832-825-1271 Fax [email protected]

mailto:[email protected]

Robert C. Green, MD, MPH Associate Professor of Medicine Division of Genetics, Department of Medicine EC Alumnae Building, Suite 301 41 Avenue Louis Pasteur, Boston, MA 02115

December 2, 2015

To Whom it May Concern:

I am delighted to write in full support for the Laboratory Genetics & Genomics specialty training proposed by

the American Board of Medical Genetics and Genomics (ABMGG).

I am the principal investigator of the NIH-funded MedSeq and BabySeq Projects, the first clinical trials to

empirically study the use of whole genome sequencing in the practice of medicine in adults and newborns.

Through these, I have had tremendous firsthand experience on whole genome sequencing data analyses,

interpretation and reporting, along with structuring outcomes collection.

As a clinician-scientist with over 20 years experience, I understand how comprehensive and holistic

interpretation of genetic test results are critical to ensure accurate diagnosis and management of patients.

Moreover, this approach will lead to a more unified diagnostic health system by bringing together separate

disciplines. For patients with inherited disorders, accurate diagnosis often requires testing that looks at both

DNA sequence changes as well as changes in chromosome copy number. Historically, this required two or more

separate tests and interpretations by two different laboratory staff. This would often require ordering two or

more separate tests from different laboratories and then receive multiple interpretations and reports. By merging

cytogenetics and molecular genetics into a single specialty of Laboratory Genetics & Genomics, this will

ultimately allow us to obtain a diagnosis for a patient with a single test and interpretation, rather than multiple

individual tests.

Streamlining this process will serve to improve healthcare delivery and patient care and reduce physician and

healthcare administrative burdens. It is therefore critical that genetics laboratory directors be able to interpret

both “cytogenetic” and “molecular” test results to ensure that clinicians and patients receive and accurate

diagnosis while reducing the burden on the patient and healthcare system.

I strongly support this important project.

Sincerely,

CLINICAL GENETICS DIVISION

MEDICAL GENETICS EDUCATION

& TRAINING PROGRAMS

GERALD FELDMAN, MD, PHD, FACMG

PROFESSOR

DIRECTOR, CLINICAL GENETICS DIVISION

DIRECTOR, MEDICAL GENETICS

RESIDENCY AND FELLOWSHIP PROGRAMS

[email protected]

MICHELLE CICHON, MS, CGC

ACADEMIC SERVICES OFFICER II

MANAGER, MEDICAL GENETICS RESIDENCY AND

FELLOWSHIP PROGRAMS

[email protected]

ANGELA TREPANIER, MS, CGC

ASSISTANT PROFESSOR

DIRECTOR, GENETIC COUNSELING

GRADUATE PROGRAM

[email protected]

ERIN CARMANY, MS, CGC

ASSISTANT PROFESSOR

ASSOCIATE DIRECTOR, GENETIC COUNSELING

GRADUATE PROGRAM

[email protected]

_____________________________________

540 E. CANFIELD • 2375 SCOTT HALL • DETROIT, MI • 48201 • (313) 577-6298 • www.genetics.wayne.edu

December 3, 2015

To Whom it May Concern:

I am writing to express my full support for the Laboratory Genetics & Genomics

specialty training proposed by the American Board of Medical Genetics and

Genomics (ABMGG). I have been a director of a CLIA-certified Molecular

Genetics Laboratory for over 25 years and have trained numerous fellows in

ABMGG-accredited laboratory training programs. As a current Program

Director and Board-certified Clinical Geneticist and Clinical

Biochemical/Molecular Geneticist, I understand why comprehensive and holistic

interpretation of genetic test results is critical to ensure accurate diagnosis and

management of patients. Moreover, this approach will lead to a more unified

diagnostic health system by bringing together heretofore separate disciplines.

For patients with inherited disorders, cancer or at risk for genetic diseases,

accurate diagnosis requires expertise that spans genomic medicine – including

DNA sequence changes as well as changes in chromosome copy number.

Historically, this required two or more separate tests and interpretations by two

different laboratorians. As a clinician, this would often require ordering two or

more separate tests from different laboratories and then receive multiple

interpretations and reports. Developing a new training track that blends

cytogenetics and molecular genetics into a single specialty of Laboratory

Genetics & Genomics will ultimately allow a qualified, Board-certified

laboratory director to provide a comprehensive and unified interpretation to the

clinician to aid in establishing a diagnosis or treatment plan for a patient. This

will serve to improve healthcare delivery and patient care and reduce physician

and healthcare administrative burdens. In this evolving field of precision

medicine, it is therefore critical that genetic laboratory directors be

comprehensively trained in genomic medicine – that is, to interpret what has

been historically separated as “cytogenetic” and “molecular” tests. Genomic

medicine is no longer amenable to such separation – we must ensure that

clinicians and patients receive an accurate diagnosis from a board-certified

laboratory director who understands and can interpret such tests.

Sincerely,

Medical Director, Division of Laboratory Genetics and Molecular Pathology

Detroit Medical Center University laboratories

mailto:[email protected]

AMERICAN BOARD OF MEDICAL GENETICS AND GENOMICS

hereby certifies that

<<Name>>

having fulfilled the requirements and having successfully passed

the examination of this board is hereby certified as a

Diplomate of the American Board of Medical Genetics and Genomics in

Laboratory Genetics and Genomics

Maintaining this certification requires full participation in the ABMGG Maintenance of Certification Program.

___________________________ __________________________ Chair Chair-Elect

___________________________ ___________________________ Secretary Treasurer

September 1,20XX December 31, 20XX

ISSUED EXPIRES

Certificate Number <<cert #>>

A Member Board of the American Board of Medical Specialties

application for specialty certificate...application for specialty certificate upon completion,...

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