Practical Genetic Counseling For The Laboratory - (3. Laboratory Infrastructure)

3
Laboratory Infrastructure
DANIELLE LAGRAVE AND JOY B. REDMAN
Genetic testing is a complex and multifaceted field requiring specially trained person-
nel as well as specially designed instrumentation and analytic software. Laboratories
that perform genetic testing require specialized infrastructure and support to ensure
that this complex testing is performed accurately. To this end, many genetic labora-
tories use genetic counselors as integral members of the genetic testing team. Just as
genetic counselors (GCs) in the clinical setting interact with other clinicians (physi-
cians, nurses/nurse practitioners, midwives), technicians (ultrasonographers, phle-
botomists), and support staff (managers, administrative personnel, schedulers), lab
GCs similarly interact with a variety of staff. The specific duties of lab GCs, covered
in the other chapters, vary to some degree based on their specific focus (e.g., molecu-
lar genetics vs. cytogenetics) and variations in protocols among laboratories, but in
general they focus on patient care/case management and client/clinician support. To
perform these common functions and the myriad of unique and lab-specific roles that
GCs fill, they rely on the many other laboratory professionals who are also key mem-
bers of the genetics laboratory team.
Genetic laboratories vary greatly in that they may offer a large testing menu or
focus on targeting specific disorders or testing methodologies, or they may focus more
on research instead of clinical testing. Some genetic laboratories specialize in specific
Copyright © 2017. Oxford University Press, Incorporated. All rights reserved.
types of disorders, such as connective tissue disorders, or may only perform a certain
type of testing, such as microarray analysis or cell-free DNA screening. Others may
test for a wider variety of disorders but still specialize in a particular area, such as
carrier screening, neuromuscular disorders, or oncology. Laboratories may be based
in academic institutions or exist as privately or publicly held commercial entities.
Genetic laboratories may be small or large, standalone specialty labs or part of a larger
reference laboratory, academic or commercial. Given all the types of genetic laborato-
ries that exist in the United States and worldwide, there will be differences in how they
operate, but they will also, by the nature of the testing, have much in common. The
purpose of this chapter is to help the reader gain an understanding of the personnel
who are often associated with laboratory operations, their training and responsibili-
ties, and the ways in which the laboratory GC may interact with these individuals. In
this chapter, the term “genetic laboratory” refers to the individual corporate or aca-
demic entity. The term “lab” refers to the various specialized laboratories within those
corporate or academic institutions.
29
Practical Genetic Counseling for the Laboratory, edited by McKinsey L. Goodenberger, et al., Oxford University Press, Incorporated,
2017. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/cityuhk/detail.action?docID=4828920.
Created from cityuhk on 2023-08-10 04:03:31.
30 P ractical Genetic Counseling for the L aboratory
Laboratory Staff
Staff in genetic laboratories usually fall into one of three categories: laboratory or
technical (the individuals who design new tests, perform clinical testing, and inter-
pret and report results); support (the people who order and maintain reagents, triage
and direct specimens to the correct laboratory, address questions and requests from
the client or clinician, perform quality assurance (QA), and ensure that the lab has
everything needed to run and report the tests); and administrative (the people who
manage the lab and handle activities such as billing, QA, and compliance). Laboratory
GCs don’t precisely fit into any of these categories. Perhaps they fit best in the labora-
tory/technical area, as they are professionals with an advanced education in genet-
ics and may be involved in writing genetic test reports or comments, suggesting new
tests, and helping clients with test interpretation. However, laboratory GCs also play
a support role in the laboratory as they address questions and facilitate requests from
individuals and facilities sending testing to the lab and provide support to marketing
and sales. An overview of laboratory personnel is provided in Table 3.1.
Laboratory staff includes lab technicians and technologists of many levels and
skills, scientists with different levels of education and backgrounds, and laboratory
directors and/or medical directors. The support staff typically includes technicians
who process the samples and maintain reagents needed by each internal lab, infor-
mation technology (IT) personnel for data management and bioinformatics support,
client services, and marketing/sales. Lab administrative support, QA and compliance
specialists, billing personnel, and lab managers serve to round out the administrative
side. These three groups, working together, make for a diverse but complete team.
When the three parts of the genetics lab work well together, their varied skills are
combined to build a cohesive lab environment to meet the company’s needs and to
provide excellent patient care by providing accurate test results in a timely fashion.
L A B O R AT O R Y T E C H N I C I A N S
Lab technicians are often employed in support positions that do not necessarily
require specific scientific or medical knowledge and may, or may not, require certi-
fication as a medical lab technician (MLT). One example of a role that generally will
not require certification is the initial intake of specimens into the genetic laboratory
(specimen processing, accessioning), where the lab technicians perform the first set of
checks to ensure that the correct test is performed on the correct sample: peeling the
layers of labels off the sample containers to make sure they all match and there has not
been a sample error and confirming that demographic information and unique identi-
fiers match between the paperwork and samples. The lab technicians also route the
samples received to the appropriate lab, scan any associated paperwork into the labo-
ratory information system (LIS), and link it to the patient sample and test order. If
there are any problems with the sample, order, or paperwork, they will often identify
the issue and begin the work to resolve it. Lab technicians may also work within the
labs that actually perform the requested testing. In this position they usually have or
learn more specific knowledge pertaining to the samples, tests, and issues particular
Table 3.1 Laboratory Personnel
Lab Personnel Education General Certification

Lab Technician High school diploma/equivalent
Lab Technologist Associate degree program in CAP technologist, molecular
medical laboratory technology, MB(ASCP), MLS(ASCP)
additional training
Medical Bachelor’s degree in one of MLS(ASCP) or MLT(ASCP)
Technologist the following: In CA: CLS (clinical genetics
• Clinical or medical molecular biologist)
laboratory science
• Medical technology
• Chemical or biological
sciences
Additional clinical training
Cytogenetics Bachelor’s degree in one of CLSp(CG)(ASCP), Cyto: CG
Technologist the following: (ASCP)
• Clinical laboratory science In CA: CLS (clinical
• Chemistry cytogeneticist scientist): see
• Biological sciences above
Laboratory • PhD or equivalent degree ABMGG certification in the
Director • Additional training in applicable clinical specialty
applicable clinical specialty
• Formal training in
laboratory medicine
Medical Director • PhD, MD, or equivalent ABMGG or American Board
degree of Pathology certification
• Additional training in in the applicable clinical
applicable clinical medical specialty
medical specialty
• Formal training in
pathology, laboratory
medicine, or both
Laboratory Bachelor’s degree in one of MT(ASCP) applicable to the
Manager the following: area(s) of responsibility
• Clinical or medical
laboratory science
• Medical technology
• Chemical or biological
sciences
Additional clinical training
Laboratory • Bachelor of science or MT(ASCP) or equivalent
Manager or equivalent degree certification
Supervisor • Advanced degree in
laboratory sciences and/or
business administration
to that laboratory, thus enabling them to identify more subtle issues that may need to
be addressed prior to testing. These lab technicians will review the test orders for each
sample, flagging potential order errors for follow-up and correction; confirm that all
electronic and demographic information and/or required paperwork (e.g., patient his-
tory forms, pedigrees, and previous test results) and all necessary information (e.g.,
the indication for testing, family history, ethnic background) have been received, and
reach out to clients/clinicians when needed paperwork or information is missing; and
ensure that the sample type and quantity is sufficient for the testing requested.
Technicians also perform basic laboratory-specific duties. These positions usually
do require certification as an MLT and may involve a variety of activities, such as stock-
ing reagents and cleaning glassware and equipment, or technical tasks such as DNA
extraction in a molecular lab or metaphase capturing in a cytogenetics lab. The College
of American Pathologists (CAP), Clinical Laboratory Improvement Amendments
(CLIA), and state-specific regulations may limit what a technician is allowed to do in a
laboratory. To become certified by the American Society for Clinical Pathology (ASCP),
one of the largest certifying agencies for both pathologists and laboratory profession-
als, technicians need some combination of an associate’s degree (or equivalent hours
of academic credit from an accredited university); a specific number of hours of chem-
istry and biology credits; experience in specific laboratory areas; and completion of an
accredited MLT program or completion of a 50-week U.S. military medical laboratory
training course (ASCP n.d.). Some states require that lab technicians be licensed. They
generally work under the supervision of a technologist or the laboratory manager
(Bureau of Labor Statistics 2015).
GCs work closely with the technicians, especially those who process the samples
and paperwork coming into the specific lab that will be performing the testing.
Clinicians often contact lab GCs about urgent samples before they actually arrive in
the laboratory. The GC may alert the processing technicians to watch for the sample
so that the test orders may be reviewed immediately and ensure that they match the
test(s) the clinician wanted performed. If there is an error, the orders may be clarified
and rectified immediately. GCs also work closely with the processing technicians to
develop standard procedures to determine when and if a sample needs to be reviewed

by a GC prior to being sent to the laboratory for testing. Reasons why a GC may need
to review a sample are based on (1) sample type (all prenatal samples may be reviewed
whereas blood samples may not be), (2) indication for testing to ensure appropriate-
ness, and (3) family history and clinical information requiring GC review. In other
words, certain indications might serve as a red flag to the technician, based on the
training provided by the GC. Therefore, the technicians are often the personnel who
will flag an order as potentially incorrect or as needing review by a GC.
L A B O R AT O R Y T E C H N O L O G I S T S
Technologists do most of the actual “wet work” in the laboratory; in other words, they
perform the tests for the lab in which they work. Technologists are required to have a
bachelor’s degree and may be required to be licensed in some states, such as California.
This may require a general certification as a medical laboratory technologist (earning
certification as a medical lab scientist [MLS]) or a specific certification in the genetic
La bo ra to r y I n fra s tr u ctu re 33
area in which they work, such as molecular biology (MB) or cytogenetics (ASCP n.d.,
Bureau of Labor Statistics 2015). Certification of technologists can be done via ASCP,
just as that of the technician. Requirements for certification depend on the area of
specialization, but all require at least a baccalaureate degree from an accredited college
or university, with some level of coursework in biology, mathematics, and chemistry,
and either experience in the lab in which they wish to specialize or specific training in
that specialty area through an accredited education program.
Depending on the laboratory in which they work, a technologist’s job responsibili-
ties may include preanalytic work such as PCR setup or cell culture and postanalytic
tasks such as the examination and analysis of sequencing or cytogenetic or biochemi-
cal results. As cytogenetics, biochemical, and molecular genetic laboratories run very
different types of assays that require specialized knowledge, the type of work done by
the technologists in each of these labs will be very different. In the molecular labora-
tory technologists may use a variety of molecular techniques such as next-generation
sequencing, Sanger sequencing, multiplex ligation dependent probe (MLPA), and
Southern blot. In the biochemical genetics lab they may use instruments such as
the tandem mass spectrometry (liquid chromatography–tandem mass spectrometry
[LC-MS/MS]) to run amino acids, organic acids, and other individual analytes. The
cytogenetic technologists set up cultures on amniotic fluid, chorionic villi, blood,
bone marrow, and tissue for karyotype or prepare those samples for direct testing by
fluorescence in situ hybridization (FISH) or microarray. Harvesting the cultured cells,
staining slides, and extracting DNA for the microarray and the analysis aspects of
these tests also fall under their purview.
When multiple tests are ordered on a single specimen, especially one with limited
volume, the technologists may ask the GCs to determine the priority of testing. This
may occur when a small amount of amniotic fluid is received with multiple orders
(e.g., karyotype, FISH, and DNA analysis for cystic fibrosis). In such cases, the GC will
contact the ordering provider and work with him or her to determine the best use of
the limited sample and which results might be needed urgently and thus should be
prioritized. Another instance where technologists may seek assistance from the lab
GC is when, upon reviewing the indication(s) for testing, they flag a case as potentially
needing different or additional testing. For example, microarray is ordered on an adult
female with an indication of a child with a deletion on one chromosome and a duplica-
tion on another. The technologist recognizes that the child might have an unbalanced
translocation, in which case an array on the parent would be an inappropriate test, as
it would not be able to identify if the parent carries a balanced translocation or not.
The technologist would flag this case for GC review, and the GC would contact the
provider to obtain additional information, reports on the child and make test change
recommendations, if appropriate.
Laboratories usually employ at least one supervisor. CLIA requires specific educa-
tion and experience for an individual who supervises a high-complexity laboratory
(see Table 3.1). Supervisors are in charge of interviewing and hiring staff, performing
or assisting with new staff training, providing guidance and oversight to lab staff when
troubleshooting assay problems, and arranging coverage schedules to ensure that the
stated turnaround times are met. Each genetics laboratory will have its own supervi-
sor requirements as well, and these may exceed the CLIA requirements. Laboratory
supervisors must meet the educational requirements of a technologist and must have
additional experience in a high-complexity laboratory. The genetics lab may require
lab-specific experience in order for an individual to qualify for a supervisory position.
When the lab employs a sufficient number of technologists and technicians, each
area of the lab may employ a “lead” or “leads,” someone who has extensive experience
in that area and acts as a liaison who takes a primary role in troubleshooting between
the other technologists in that area and the lab supervisor. Each genetics laboratory
will have its own requirements that must be met for someone to become a lead, but in
general these individuals have in-depth knowledge of and experience in their area of
the lab and have demonstrated critical reasoning skills.
The lab GC often works with the bench leads and lab supervisors rather than with
individual technologists. This allows the GC and the lead or supervisor to develop a
working partnership and ensures that the lead/supervisor is aware of both the issues
brought to the GCs and of any requests the GCs may make of the technologists, allow-
ing the supervisor to prioritize requests, work them into the regular workflow, and
ensure that lab processes are not disrupted.
L A B O R AT O R Y D I R E C T O R S
Current education and experience requirements for laboratory directors are summa-
rized in Table 3.1. Laboratory directors have a PhD, an MD, or their equivalent and have
done their training and fellowship in the area of molecular genetics, cytogenetics, and/
or biochemical genetics. They are board certified or eligible for board certification by the
American Board of Medical Genetics and Genomics (American Board of Medical Genetics
and Genomics 2016). They may have board certification in any or all of four special-
ties: clinical genetics and genomics, clinical biochemical genetics, clinical cytogenetics
and genomics, and clinical molecular genetics and genomics. As some laboratory direc-
tors are MDs, they may also have board certification in medical biochemical genetics,
molecular genetic pathology, and/or pathology. The educational and licensing require-
ments for a laboratory director are determined by CAP and different state regulations.
New York state, for instance, requires that a director signing out cases on state residents
hold a certificate of qualification (COQ). For a COQ in either cytogenetics or molecu-
lar genetics, one must prove sufficient laboratory experience (Department of Health,
Wadsworth Center, New York State n.d.). In comparison, the state of California requires
proof of certification from the American Board of Medical Genetics and Genomics
(ABMGG; California Department of Public Health 2016) and an oral examination.
Laboratory directors oversee and manage the overall operation and administra-
tion of the laboratory; however, they are primarily responsible for the quality of the
test results and interpretation of those results included on the genetic test report. To
ensure that the results are correct, the lab director may review the work performed
in the lab by the technologist, the calls made by any software that may be used in the
testing process, and the indication and family history information provided by the
clinician. Results are then evaluated in light of all available information to ensure that
they make sense. They work closely with their GCs. Of particular importance is when
missing or incomplete clinical information has been provided to the lab. If a sample
is tested and the director feels that he or she would like more information before
reporting the results, he or she may ask the laboratory GC to obtain additional, or per-
haps more specific, information regarding the patient, the family history, or previous
test results. In addition, the director may ask for more information if a result does not
make sense in light of the clinical data provided. For example, a beta globin common
mutation assay may indicate that a patient has one copy of the hemoglobin S muta-
tion while the clinical information indicates that the patient has sickle-cell disease.
There may be several valid explanations for the observed inconsistency: (1) incorrect
clinical information was provided or logged, (2) the patient actually has a related dis-
order, sickle-beta thalassemia, and additional testing would be needed to identify the
beta thalassemia mutation, (3) the initial sample submitted was mislabeled, or (4) the
provider was trying to determine if the patient had sickle-cell anemia versus sickle-
cell trait, and this was not communicated clearly to the laboratory. To avoid issuing a
result that is obscure or ambiguous, may need to be corrected, or may lead to an erro-
neous test interpretation by the physician, the GC may be asked to investigate before
the report is signed by the director. This will usually involve a review of the clinical
information and possibly a call to the healthcare provider to confirm the diagnosis
and review previous test results and other clinical possibilities as described above.
This may also involve working with the lab supervisor and/or technologists to verify
the labeling on the original blood tube, the extracted DNA, and the assay plate maps
to rule out a lab processing error.
The laboratory director may work closely with or direct the research and develop-
ment (R&D) group supporting the laboratory. They will guide the scientists in their
work and provide scientific direction during assay development.
The laboratory director may bring to the GC’s attention results that he or she
believes need additional explanation or that indicate the need for additional testing
of the patient or a family member. The director may ask the GC to call and discuss
these results with the ordering healthcare provider to alert the provider to the find-
ings and explain the implications of the results for the patient, the patient’s family
members, or both. These may include clearly abnormal results, variants of uncertain
significance, or unintended or unexpected results. Typically the director and GC dis-
cuss the information needed to explain the implications and ramifications of the find-
ing to the ordering provider. This provides the clinician with an opportunity to ask
questions and clarify the test result so he or she can best follow up on the finding. This
also provides the clinician with a lab contact to help coordinate any additional test-
ing needed. When providers ask questions that are outside the knowledge base of the
lab GC, or that deal with medical management or similar issues that are outside the
normal scope of practice for a GC, the GC may refer these questions to the laboratory
or medical director.
A N N O TAT O R S /VA R I A N T S C I E N T I S T S
Molecular laboratories that perform sequencing, especially next-generation sequenc-
ing, may have an additional group working to research variants identified by sequenc-
ing and to determine if the variant is likely to be pathogenic or not. As this is a
relatively new position in the genetics laboratory, these individuals have multiple titles
but are usually referred to as “variant analysts or specialists” or sometimes “variant
researchers” or “annotators.” This position has become more prevalent with the large
number of next-generation sequencing panels and whole exome sequencing tests
being performed. Many of the genes tested have been known for only a short time, so
there is little published information about variants within them. In laboratories that
perform whole exome sequencing, variant analysts are becoming central to the lab’s
ability to report meaningful results. Analysts use information from many sources to
classify a variant, such as publications demonstrating segregation of the variant with
disease within a family, or the presence of a variant in affected individuals within a
population of study, in silico analyses and predictive programs, truncation and other
functional studies, and location within a specific area or domain of the gene in ques-
tion. Many labs follow the guidelines adopted by ACMGG for reporting such variants
and will classify them as pathogenic, likely pathogenic, uncertain significance, likely
benign, and benign (Richards et al. 2015).
The analysts will often work with the GC, who might help with collecting and inter-
preting clinical and family history data from the literature and/or the patient, espe-
cially when re-review of data sources leads to reclassification of a variant.
RESEARCH AND DEVELOPMENT

Scientists with educational backgrounds ranging from a bachelor of science degree
through a PhD and/or an MD are employed in the R&D areas in most laboratories.
They are usually involved in assay development, investigation and comparison of new
and current testing platforms, and troubleshooting issues with current assays. As long
as these individuals are not running or reporting clinical samples, they do not fall
under the same regulations as do the clinical laboratory technicians or technologists
discussed above. The laboratory GC may interact with members of the R&D group in
multiple ways. Scientists will often need or want the input of a clinician while develop-
ing an assay—for example, do clients expect a reflex option in a particular assay, do
clients generally want more mutations or fewer on a panel, is a specific microdeletion
appropriate for a cell-free DNA prenatal screen, which genes should be included on a
colorectal cancer panel, and what should be reported in a whole exome study report?
In addition, for many assays, positive controls, clinical validation studies, and/or pop-
ulation studies are needed prior to launching a clinical test. The GCs may be called
upon to assist the R&D scientists by contributing clinical input on these key questions
and facilitating the procurement of positive control samples for these studies. Lab
GCs also consult on proposed Institutional Review Board applications, draft informed
consent forms, and sometimes identify key opinion leaders who might be interested
in collaborating. Scientists will often request input from the GCs to help determine
what assays to develop and how to “package” the available test components in a man-
ner that will provide the best set of test order options to the lab’s clients.
The R&D group will often look to the laboratory GC to write disease-specific
informed consents, which may be needed to satisfy the requirements of many states
(15 as of 2015). In fact, any laboratory that applies for New York state approval for
genetic testing must have a disease-specific consent form (Department of Health,
Wadsworth Center, New York State n.d.). To partner effectively with the R&D
group, laboratory GCs need to understand the advantages, disadvantages, and
limitations of the assays and the test platforms so they may discuss these issues
with clients and providers when needed. The R&D scientists provide the necessary
education to the GC about the assay, the specific results generated, and issues that
may arise. This education is also beneficial for GCs who help write standard report
templates covering the most common test results. Since many ordering providers
are not genetic specialists, it is important that reports be both complete and easily
comprehensible.
CLIENT SERVICES
Most genetic laboratories have one or more individuals physically in or proximal to
the laboratories who function as the initial point of contact for most external clients.
Depending on the size of the entire laboratory, they may also have a larger department
of individuals trained to triage and address questions received from callers intended for
one of the internal labs. These individuals may hold the title of client services represen-
tative, laboratory administrative assistant, technical representative, or other related
job title. They do not perform any of the testing itself. They are in charge of answering
some questions and triaging others to the appropriate staff. Their hands-on function
in the lab may include helping to resolve requests by clients (e.g., pulling past reports
for review by the laboratory director, requesting a DNA tube to determine amount of
specimen remaining) and responding to questions from providers about the testing
ordered, specimen requirements, and turnaround time. Some may not have any physi-
cal interaction with the samples at all. Depending on the laboratory structure, the cli-
ent services personnel may be generalized to take calls about all the assays performed
(more common when there is a general client services department) or may be special-
ized to take calls that pertain only to a specific lab, such as cytogenetics or oncology
(most common when they are within or close to the lab proper). Calls to the laboratory
may fall into many categories: turnaround time, test add and cancellation requests,
order assistance, availability of specific tests, assay-specific questions, maternal serum
screening recalculation requests, and result interpretation requests. These individu-
als have usually received on-the-job training specific to the needs of the laboratory in
which they work. Therefore, depending on their experience and time in the laboratory,
they may be able to answer many of the questions above but will need to triage some of
the calls, especially those regarding order assistance, result interpretation, and assay-
specific questions. The more complex questions are often directed to the laboratory GC.
It is important that the GC build a relationship with this person, or group of individu-
als, as they rely on each other to get the work done in the most efficient manner. For
example, while calls will be triaged to a GC, the GC may then request that this group
perform test adds and cancellations, pull samples, and perform other logistical duties
as needed.
BILLING
Laboratory GCs may or may not interact with the billing personnel. This depart-
ment is often removed from the actual laboratory. However, some GCs do work with
this group to help with insurance preauthorization and denials. They may also write
generic letters of medical necessity in collaboration with billing personnel that the
healthcare professionals may tailor for their patients when needed.
L A B O R AT O R Y /D I V I S I O N M A N A G E R S
The laboratory is usually run by a laboratory or division operations manager. This per-
son may have a PhD in the biological or chemical sciences, a master of business admin-
istration degree, or a bachelor of science degree. Medical doctors may fill this position,
as well as medical technologists or other laboratory specialists with sufficient educa-
tion to meet CLIA and state regulations. The lab manager may also serve as the super-
visor of the laboratory GC as he or she is responsible for the operations of the lab and
how the individuals who work there interact. Regardless of reporting structure, the
GC usually does work with the laboratory manager. The manager is responsible for
the overall operations and management of the laboratory, developing lab processes
intended to promote quality testing while keeping costs under control, and ensuring
that the laboratory complies with all CLIA and CAP requirements as well as any state
regulations (e.g., New York state regulates the tests themselves; California regulates
the type of personnel who can perform each step of each assay).
The laboratory manager is often one of the individuals who works with the GC
to discuss what tasks are needed in the lab and what tasks are appropriate to the
GC’s skill set. The GC can also keep the lab manager updated about client feedback
and changing needs. For example, if the GC receives multiple complaints about
turnaround time for a specific assay, the lab manager may decide to change the
setup and reporting schedules to decrease the turnaround time after discussion
with the GC.
QUALIT Y ASSURANCE
QA is an integral function of any laboratory. Depending on the size and needs of
the laboratory, each individual lab may have its own QA representative or there may
be one or more covering the entire laboratory. The QA department oversees and
monitors laboratory QA practices and activities to ensure they conform with inter-
nal and external policies and regulations. They ensure that the laboratories are in
compliance with the outside regulatory agencies, as well as their internal standard
operating procedures (SOPs). As a result this group is usually the one that interacts
heavily with any laboratory audit from regulatory agencies. Activities that may fall
under their purview are instrument calibrations, proficiency testing, investigations
into result discrepancies, and meeting with inspectors such as those from CAP and
New York state.
All clinical laboratories have SOPs that detail how each assay is run from start to
finish. It is important that all the appropriate staff members are trained and signed
off on every SOP for every assay they perform. With any amendment, retraining
must occur and be documented. The QA specialist makes sure this is done and that all
records are filed with all signatures and training dates.
Record retention policies are set by each laboratory. Each laboratory must comply
with the state laws, as well as Health Insurance Portability and Accountability Act
(HIPAA) regulations (Center for Medicine & Medicaid Services n.d.). Along with the
laboratory records, records that may need to be retained include those generated by
the laboratory-based GCs. Clinical GCs should also be familiar with these regulations
as they must retain their clinical records for a set amount of time. The laboratory-
based GCs normally have telephone logs and email and communication records (often
related to positive results). Each laboratory must comply with the state laws and
determine its own retention policies to meet them. The compliance or QA depart-
ment will often oversee this process and would serve as a consultant to the GC for any
record-retention questions.
For those laboratories that choose to offer genetic testing to residents of New York
state, special regulations apply. Each test must be individually submitted to the state
Department of Health’s Wadsworth Center for approval prior to making it available to
the citizens of New York. The QA specialist may assist in writing up the submissions
for NY state approval and may request the GC’s assistance to address specific issues
(Department of Health, Wadsworth Center, New York State n.d.).
There are three specific instances in which the QA representative works with the
GC. First, the GC must undergo training and sign off on such training for all SOPs
relevant to their specific position within the laboratory. The QA specialist may main-
tain records of this training as well as records of certification and licensure for the
GCs. Second, GCs may write their own SOPs that govern some of their tasks to ensure
standardization. These may address abnormal result communication and their test
verification processes, and GCs will often work with the QA specialist to assist with
formatting and ensure that all required aspects of the document have been addressed.
Third, when a test result requires amendment or correction, the GC may work with the
QA department to provide the required notification to the medical provider. The GC is
often the one who is charged with communicating a revised result back to the client,
along with discussing with the provider what occurred and why the report required
a correction. Clear documentation needs to be completed for each case, especially if
any kind of lab error resulted in the original, erroneous report, and the GC is often
involved in part of that documentation process.
COMPLIANCE
The compliance department or officer provides education, training, and updates to
prevent illegal, unethical, or improper conduct. The lab-related responsibilities of the
compliance department are wide-ranging and may include HIPAA training, informed
consent issues, prevention of improper billing, and anti-kickback and Stark rules
enforcement. Verifying and monitoring the licensing of laboratory personnel may
fall under either compliance or the QA department. Compliance department staffers
may work with laboratory personnel, including the GCs, to discuss a difficult case
to make sure that HIPAA rules are respected. Compliance personnel may work with
a GC to develop informed consent forms or an entire process to monitor incoming
samples. For example, most laboratories have a process in place to capture samples
submitted on minors for Huntington disease presymptomatic testing. The GC is
often involved in these decisions with compliance personnel, lab managers, and the
medical directors.
I N F O R M AT I O N T E C H N O L O G Y / D
ATA M A N A G E M E N T /
B I O I N F O R M AT I C S
Most clinical laboratories rely on IT personnel to automate much of the work involved
in accessioning, processing, and tracking samples as well as reporting results. Beyond
the basic LIS used in the laboratory to track samples, orders, and results, many genet-
ics labs need specialized IT support known as bioinformatics. Bioinformatics is a
branch of IT that develops software tools for analyzing and understanding biological
data. Bioinformatics is necessary for many of the sophisticated platforms currently
in use, such as cell-free DNA screening tests and next-generation sequencing/whole
exome sequencing. These tests generate large amounts of data that require powerful
analytic tools and storage.
There are several instances in which technology/bioinformatics is used in the
genetics lab. Many molecular tests are run in batches of 48, 96, or 384 samples. For
labs to track each sample and ensure that the correct result is associated with the cor-
rect patient, they may rely on molecular barcoding, a method that attaches unique
sequences to each patient’s sample, allowing samples from multiple patients to be run
at the same time while enabling the computer to identify which sequence came from
which patient. Many labs use sophisticated test algorithms to analyze test data and
identify mutations, sequences of interest, or duplicated/deleted material; map these
to a reference genome; and determine if any alteration is likely to be disease-causing
or not. Array software is annotated with the results of genome-wide association stud-
ies so that copy number variants may be correctly classified. Serum screening algo-
rithms take test results and use those to modify risk for specific congenital disorders.
Specialists in bioinformatics create, maintain, troubleshoot, and improve the software
and algorithms, working closely with the laboratory to ensure that the lab’s needs
are met.
GCs may work with IT to build, maintain, and query databases of genetic informa-
tion and clinical information. These databases may be used by the laboratory, medical
directors, or the GC to consolidate all the information about each patient into one
location so that an individualized report using all of the available clinical information
may be created. Such databases also allow the lab to gather relevant patient data based
on varying criteria for publication purposes.
In many laboratories, IT support is needed to develop alert lists that will collect
certain positive results so that they may be called or faxed directly to the ordering pro-
vider or other designated entity. These may include alerts for prenatal tests or results
that may require explanation beyond that usually included in a typical report.
Computer databases that allow the access and documentation of staff actions
are essential in the genetics laboratory. On occasion, lab personnel will identify a
problem that must be communicated to the client. Such problems can range from
rather straightforward issues, such as missing clinical information or an amniotic
fluid culture that is growing poorly, to more complex issues, such as both 46,XX
and 46,XY cells observed in a sample or the need for a sample to be repeated, which
results in the delay of a critical result. Such databases may also be used to document
information the client provides to the lab. This might include (1) family information
and records for an incoming prenatal sample, (2) the need for additional cell cultures
for a send-out test, (3) the need for an expedited result, and (4) missing information
necessary to run or interpret a test result. These records are often accessed and used
by many members of the laboratory, both for documentation and status checks and
to pull information needed for interpretation, reporting, and, occasionally, publica-
tion. It may also be used to check if SOPs were followed in a case where a problem
occurred.
Daily or weekly reports may be generated that contain helpful information regard-
ing the number of samples received for each test, as well as a list of samples that have
missing clinical information. Given the importance of performing the right test, cer-
tain test orders may need to be reviewed by a GC prior to running, and the required
reports needed to identify these are generated with the help of IT.
Most genetic laboratories have an external website, and most companies have
intranet sites. The information on them varies widely, as do the writers and cura-
tors. IT personnel are integral in developing the look and “feel” of the public website
and in maintaining the information and links to internal information such as patient
brochures, test FAQ sheets, and technical information as well as any links to out-
side sources that may be useful to customers. These may include test search engines,
patient support sites, and sites with gene/disease information.
S A L E S /M A R K E T I N G
The sales team is responsible for engaging with current and potential customers of the
laboratory and persuading them to use the services of the laboratory they represent.
They will demonstrate the lab’s strengths and try to make sure the customers’ needs are
met. The marketing department creates materials to support sales and create the value
proposition for the client. They may emphasize the services the laboratory can per-
form, the accuracy of its testing, the processes in place to minimize sample errors, and
the specificity or breadth of the lab’s test menu. The marketing department may have
GCs on staff or may request involvement of the lab GCs on specific projects. Since the
lab GCs talk with medical professionals daily, they have a good understanding of what
clients are looking for and need. Many GCs are members of one or more professional
societies, and such participation, along with attendance at national genetics meetings,
keeps them abreast of the evolving world of genetic testing. This information may be
valuable to the marketing staff so that they know what the competition is doing as well
as what the medical community is looking for in the near, and distant, future.
GCs may assist the sales team by joining them on client visits, giving formal and
informal presentations, spending time in the professional meeting booth at genetics
conferences, and providing training in specific areas of genetics as requested by sales.
Since the GC can often discuss specific tests in detail and compare them to similar
tests on the market, the sales reps may ask a GC to accompany them to a potential cli-
ent or physician office to help ensure clear communication, as well as to demonstrate
the resources available to clients who choose to send their tests to that particular
laboratory. When accompanying sales reps to a healthcare provider’s office or hospital
lab, the medical professionals there will often ask questions that they may not have
thought to ask the sales team, in this way building a different type of bond between
the provider and the laboratory.
Booth attendance at professional meetings is a common duty for many lab-based

GCs; it is a time to meet face to face with clients known only by telephone up to
that point. It is one more tool in the arsenal for building and strengthening work-
ing relationships between the GC and clients. Getting a genetic test done correctly
and efficiently is often a team effort. Lab-based GCs often rely on clients to give
them a heads up for a critical sample and provide them with necessary records.
Anything that builds trust and a working relationship between a client and the lab
is worthwhile.
The marketing team will partner with the lab GCs to develop and write literature
describing the testing offered by the lab. Marketing personnel are in charge of devel-
oping the technical literature, which describes the methods of testing, the diseases
being tested for, the limitations of the test, and the sensitivity and specificity of the
test. They are also in charge of developing any patient and physician support materials
the lab wishes to create. Patient brochures may discuss common screening tests, com-
paring different tests that look for the same condition, as there will be aspects of each
test that may make it appeal to some patients but not to others. FAQ sheets, useful
for both patients and providers, explain when tests are useful and when they are not.
They attempt to direct providers to choose the correct test for their patients and to
provide the appropriate supporting documentation, such as test reports on previous
family members or the indication for testing. The marketing staff will often call upon
the GC to assist with these tasks.
Case Example
Lab personnel interact with the lab GC throughout each day. In many labs, other than
client services or processing technicians, it is primarily the GCs who contact outside
medical professionals and take calls from them with regularity. Therefore, the GCs fill
a needed niche, acting as a bridge between the laboratory and the clinician. The follow-
ing scenario illustrates just a few ways in which this collaboration occurs.
S A M P L E A R R I VA L
A blood sample arrives in the lab with a request to run full gene sequencing for cystic
fibrosis (CFTR). Because of the frequent incorrect orders for CFTR sequencing instead
of the common mutation panel, the order is flagged by special software and an email
alert is sent to the GC for review.
TEST REVIEW
The test is ordered on a 24-year-old, pregnant Caucasian female with no symptoms
and no family history. The indication is marked as “screening.” The GC first alerts the
lab technician to hold this sample while the test is being verified. She calls the ordering
physician to discuss the order and finds that the MD actually wanted routine cystic
fibrosis (CF) screening, as the patient is pregnant and has not had screening in the
past. The GC documents the request for the test change and follows the lab’s SOP
regarding test order changes. The GC communicates the test change to the lab techni-
cians who process the sample to alert them that the test will be changed to the CF
screening panel. Once the test change has been processed according to the lab SOP
and the new test order is in the system, the technician performs the test add, relabels
the sample with the CF carrier screen test code, and alerts the lab technologist that
the sample is ready to be run. The technologist runs the CF screening panel and the
lab director reports it as heterozygous for deltaF508, the most common CF mutation
seen in Caucasians.
P O S I T I V E R E S U LT S
The lab director alerts the GC when the CF result has been reported. The GC phones the
physician’s office about this CF carrier result. She speaks with the nurse and explains
that the next step is to screen the father of the baby to determine his CF carrier status.
She asks the office to alert her when the father’s sample is drawn and submitted so she
can ensure there are no delays in reporting the results and so the lab will be aware that
one member of the couple has already been identified as a CF carrier.
F O L L O W -U P T E S T I N G
The nurse calls the GC when the father’s sample is drawn to provide his name and
date of birth. The GC monitors the arrival of the sample and confirms the correct test
was ordered, then alerts the processing staff and the lab technologist running the CF
screening panel that this is a priority sample (since the couple is pregnant and the
mother is a known CF carrier). The lab technician then lets her know when the result
goes up for the director’s review. This allows the GC to watch for it to be finalized so
that the physician receives the result as quickly as possible. In this case, the father of
the baby is also heterozygous for a CF mutation, G542X. The lab director alerts the GC
to call the physician about the positive result.
The GC calls the physician’s office with the father’s result. She discusses the one-
in-four risk that the fetus may have inherited a mutation in the CFTR gene from
both parents and will have CF. Along with this explanation, she recommends that the
patient meet with a GC for an in-depth discussion.
P R E N ATA L T E S T I N G
The patient’s GC calls the lab GC to alert her that an amniocentesis is being done and
amniotic fluid will be sent to the lab for CFTR testing along with a karyotype. The
molecular lab GC contacts the cytogenetic lab GC to inform her about the incom-
ing sample as well as the prioritization of the desired testing. In this case, the first
priority is the CF test and the second is the fetal karyotype. The cytogenetics lab
technician knows to aliquot a specific volume of amniotic fluid for CFTR testing and
to grow backup cultures for possible additional testing. The cytogenetics GC will also
alert the molecular genetics lab of the amniotic fluid sample that is coming in and
will manage any logistics between the two labs. Depending on the size of these labs,
there may be multiple GCs in each lab: they often work together to manage complex
prenatal cases.
PROBLEM SAMPLE
In this case, the amniotic fluid received is quite bloody. The cytogenetics lab technolo-
gist contacts the GC to ask if an aliquot of direct amniotic fluid should still be sent to
the molecular lab or if they should set up cultures only. As maternal blood may con-
found DNA results on direct amniotic fluid, and culturing amniocytes reduces the risk
of maternal cell contamination, the GC decides in collaboration with the lab supervi-
sor not to send direct amniotic fluid to the molecular lab but to set up all of the fluid
to culture. The GC notifies the patient’s GC to alert her that there will be a delay for
the CF results due to the bloody amniotic fluid and that the lab will use maternal blood
from the original CF carrier screen on the patient to rule out maternal cell contamina-
tion when the CF testing is performed on the cultures.
Coordinating a prenatal molecular study often involves the GC working with the
technologists to make sure the sample is processed and run as quickly as possible.
The GC will typically make sure that maternal cell contamination studies are run and
reported, and may be involved in putting together the clinical and parental lab data
needed for the director to sign out the prenatal case when ready.
D E L AY E D R E S U LT S
A week after receipt of the amniotic fluid, the GC receives an alert from the cytogenet-
ics technician in the tissue culture room that the cells are growing more slowly than
normal. This is often a problem related to a bloody amniotic fluid sample. She again
contacts the patient’s GC to let her know of the added delay. When testing is finished,
the prenatal study is given to the GC by the lab director to communicate results back
to the provider and/or clinical GC. In the meantime, the cytogenetics lab will still be
holding cells from the prenatal study in case they were needed for repeat testing, and
the GC alerts that group that those cells may be discarded.
Future Directions
GCs are working in most clinical genetic laboratories in the United States. It is difficult
to imagine how a clinical genetics lab would work without one or more GCs, as they
are integral members of the laboratory team. As volumes increase and technology
rapidly progresses, labs are relying more and more on automation to help streamline
the process and keep costs low while maintaining accuracy. Due to this increase in
automation, it is possible that fewer personnel will be required in the lab to perform
the tests: fewer technologists may mean fewer supervisors, with one supervisor cover-
ing multiple labs. With the advent of next-generation sequencing, bioinformatics has
become an increasingly important aspect of laboratory operations. It is reasonable to
predict that these specialists, who use computer science engineering, mathematics,
and statistics to analyze complex biological data, will become increasingly important
and integral members of the lab team. With the increased use of automation and the
necessity of using bioinformatics algorithms not only to perform some of the more
complex tests but also to analyze and help interpret the large amount of data pro-
duced, bioinformaticians will likely become involved in test development, modifica-
tion, and daily lab operations.
References
American Board of Medical Genetics and Genomics (2016). Training Options. [online] Available
at: http://www.abmgg.org/pages/training_options.shtml.
ASCP (n.d.). ASCP Board of Certification Requirements. [online] Available at: http://www.ascp.org/
content/Board-of-Certification/GetCertified#tabs-eligibility [Accessed 24 May 2016].
Bureau of Labor Statistics (2015). Medical and Clinical Laboratory Technologists and Technicians.
[online] Available at: http://www.bls.gov/ooh/Healthcare/Medical-and-clinical-laboratory-
technologists-and-technicians.htm [Accessed 24 May 2016].
California Department of Public Health (2016). Information About the Clinical Genetic Molecular
Biologist License. [online] Available at: https://www.cdph.ca.gov/programs/lfs/Pages/
ClinicalGeneticMolecularBiologist.aspx [Accessed 1 July 2016].
Center for Medicine & Medicaid Services (n.d.). Medical Record Retention and Media Formats
for Medical Records. [online] Available at: https://www.cms.gov/Outreach-and-Education/
Medicare-Learning-Network-MLN/MLNMattersArticles/downloads/SE1022.pdf.
Department of Health, Wadsworth Center, New York State (n.d.). Submission Checklists. [online]
Available at: http://www.wadsworth.org/regulatory/clep/clinical-labs/obtain-permit/test-
approval/submission-checklists [Accessed 29 June 2016].
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W., Hegde, M., Lyon, E.,
Spector, E., Voelkerding, K., & Rehm, H. (2015). Standards and guidelines for the interpre-
tation of sequence variants: a joint consensus recommendation of the American College of
Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med,
17(5), pp. 405–423.

Practical Genetic Counseling For The Laboratory - (3. Laboratory Infrastructure)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Practical Genetic Counseling For The Laboratory - (3. Laboratory Infrastructure)

Uploaded by

Copyright:

Available Formats

3

Lab Personnel Education General Certification

develop standard procedures to determine when and if a sample needs to be reviewed

RESEARCH AND DEVELOPMENT

Booth attendance at professional meetings is a common duty for many lab-based

the GC alerts that group that those cells may be discarded.

You might also like

Practical Genetic Counseling For The Laboratory - (3. Laboratory Infrastructure)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Practical Genetic Counseling For The Laboratory - (3. Laboratory Infrastructure)

Uploaded by

Copyright:

Available Formats

3

Lab Personnel Education General Certification

develop standard procedures to determine when and if a sample needs to be reviewed

RESEARCH AND DEVELOPMENT

Booth attendance at professional meetings is a common duty for many lab-​based

the GC alerts that group that those cells may be discarded.

You might also like

Booth attendance at professional meetings is a common duty for many lab-based