Clinical Molecular Genetics

Clinical Year (typically year 1): Fellows will complete 8 months of full-time (at least 40 hrs per week) training in a primary laboratory, followed by 4 months of training split between the primary laboratory and two additional laboratories (50% time for 2 months in each lab). Unless an outside funding arrangement has been approved, the year of clinical laboratory training will be funded by the program.

Research Year (typically year 2): Fellows are also required to complete one year of genetics research, with an approved Harvard faculty mentor. Funding for the research year must be secured through the Harvard faculty member or by successful obtainment of outside funding (e.g. NRSA award). In special circumstances, the research year requirement may be satisfied by working on research and development in one of the program's affiliated clinical laboratories, with funding typically provided by the clinical lab. The latter option is not recommended for candidates with little or no postdoctoral research experience. Instead, competitive candidates without prior postdoctoral research experience would be encouraged to use the second year of research as a year to begin a typical postdoctoral research experience (usually extending beyond the one year required by the ABMG laboratory fellowship).

Primary laboratory assignments and 2 month rotation assignments will be done in a "residency-match" format. Applicants will be asked to rank their laboratory preferences and laboratories will be asked to rank their applicant preferences. The program and laboratory directors will determine the final assignments.

During their laboratory training, fellows are expected to complete the following basic requirements.

1. Fellows will complete 150 logbook cases in compliance with the ABMG requirements. See http://www.abmg.org/cert-2005/05-cert-00c.htm for details
   
   
2. Fellows will become competent in the basic molecular techniques (as demonstrated through hands-on experience in the laboratory) and become familiar with an additional techniques used in clinical molecular genetics. Basic techniques include electrophoresis, PCR, Southern analysis, DNA sequencing, and available genotyping assays. Additional assays to which fellows should have exposure include but are not limited to: mutation screening techniques (SSCP, dHPLC, DGGE), additional genotyping techniques (e.g. ASO, RFLP, primer extension, TaqMan), methylation studies, microsatellite studies (e.g. instability, triplet repeat expansion, MCC, identity), and quantitative approaches (e.g. aCGH, quantitative PCR, MLPA).
   
   
3. Fellows will learn the major clinical indications for molecular testing and the clinical implications of test results. This learning is primarily facilitated through hands-on experience with cases including review of test requisitions and drafting of case reports.
   
   
4. Fellows will learn to calculate genetic risks and integrate molecular and clinical data. For example, the reporting of recurrence risks after positive results or residual risks after negative results.
   
   
5. Fellows will develop skills in communicating with referring physicians, and when appropriate, communication with patients. This includes the 10 cases required for the ABMG logbook, but also includes general exposure to the clinic.
   
   
6. Fellows will become familiar with clinical disorders amenable to molecular testing. This experience will be facilitated by involvement in the decision-making surrounding new test development as well as discussions in the didactic and discussion portions of the program.
   
   
7. Fellows will become familiar with the processes required for quality control, quality assurance, and quality improvement necessary for the management of a diagnostic laboratory. This learning will include fellow's participation in proficiency testing as well as involvement in the quality control procedures in the lab. It will also include discussions and often direct involvement in the QA/QI policies in the lab (incident reports, QI projects, etc).
   
   
8. Fellows will become sensitive to ethical issues in genetics, particularly those raised by molecular diagnostic testing. Lab supervisors and directors will involve fellows in all discussions and cases that arise in which ethical issues are a factor. These topics are also covered in the didactic and discussion portions of the program.
   
   
9. Fellows will complete a project involving either the development of a new diagnostic test or the modification of a current methodology.
   
   

Details about each laboratory are listed below:

Brigham and Women's Hospital DNA Diagnostic Laboratory
Children's Hospital Boston DNA Diagnostic Laboratory
Genzyme Genetics Molecular Diagnostic Laboratory
Laboratory for Molecular Medicine at HPCGG, Satellite Lab of MGH
MGH Neurogenetics DNA Diagnostic Laboratory

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Brigham and Women's Hospital DNA Diagnostic Laboratory

Location:	Brigham and Women's Hospital, Boston, MA
Website:	NA
Director:	Janina Longtine, MD
Staff:	5 pathologists, 3.5 technicians, lab coordinator

Test Offerings:

B-cell lymphoma (IgH - clonality)
T-cell lymphoma (TCR - clonality)
Chronic myelogenous leukemia - BCR/ABL- quantitative (B3A2, B2A2), qualitative (E1A2)
Acute promyelocytic leukemia - PML/RARA - qualitative
Follicular lymphoma - t(14:18) - BCL-2/JH rearrangements
Factor V Leiden
Prothrombin 20210G
EGFR mutation analysis in concert with LMM

Platforms:

Southern blot, PCR, RT-PCR, fragment length analysis by capillary gel electrophoresis, Genotyping, tissue microdissection

Children's Hospital Boston DNA Diagnostic Laboratory

Location:	Children's Hospital Boston, Boston, MA
Website:	NA
Director:	Bai-Lin Wu, Ph.D.
Staff:	2 geneticists, lab manager, 4 technicians

Test Offerings:

Achondroplasia/Hypochondroplas (FGFR3)
Albinism Type 1 (OCA1)
Albinism Type 2 (OCA2)
AS/PWS syndrome
Cell Culture
Congenital Fibrosis of Extraocular Muscles (KIF21A)
Connexin 26 (GJB2)
Connexin 30 (GJB6)
DMD/BMD
DNA Extraction hold or send
Doublecortin (DCX)
Factor V Leiden
Fragile X syndrome
Gilbert Syndrome/Hyperbilirubinemia Type I (UGT1A)
Mitochondrial 12sRNA
Mitochondrial MELAS
Mitochondrial MERRF
Mitochondrial tRNA-Leu
Mitochondrial tRNA-Lys
Mitochondrial tRNA-Serl
Myotonic Dystrophy Type 1
Pendrin (SLC26A4)
Prothrombin 20210 Factor II
Rett Syndrome (MECP2)
Sequencing For Specific Mutation
Smith-Lemli-Opitz (DHCR7)
Spinal Muscular Atrophy Type 1
Thrombophilia, Thermolabile Variant (MTHFR)
Uniparent Disomy (UPD)
Y Sequence PCR Detection

Platforms:

DNA Sequencing, Genotyping, Southern blot/Methylation analysis, dHPLC, MLPA

Genzyme Genetics Molecular Diagnostic Laboratory

Location:	Genzyme Genetics, Westborough, MA
Website:	http://www.genzymegenetics.com
Director:	D. Alexa Sirko-Osadsa, Ph.D. (Director responsible for training programs)
Staff:	7 ABMG-certified Clinical Molecular Geneticists (Site Director, Director of Clinical Operations, Director of Technical Operations, 4 Molecular Laboratory Directors), 8 ABGC-certified Genetic Counselors; 6 NCA-certified (CLSpMB) Laboratory supervisors; many technologists

Test Offerings:

Bloom Syndrome
Canavan Disease
Cystic Fibrosis (97 mutations and polyT polymorphisms)
Factor II (prothrombin G20210)
Factor V Leiden
Familial Dysautonomia
Fanconi Anemia Type C
Fragile X Syndrome
Gaucher Disease
Glycogen Storage Disease 1a
Hemophilia A/Factor VIII inversion
Huntington Disease
Maple Syrup Urine Disease
Maternal Cell Contamination analysis
MTHFR
Mucolipidosis Type IV
Niemann-Pick Type A Disease
Prader-Willi/Angelman Syndrome (Methylation Analysis)
Rhc/RhE and RhD genotyping
Tay-Sachs Disease
Y chromosome determination
Y microdeletion analysis
Zygosity analysis

B-cell clonality (PCR and Southern blot)
Quantitative BCR/ABL
Bone Marrow Engraftment Analysis
EGFR for drug-responsive lung cancer
T-cell clonality (PCR and Southern blot)

Platforms:

DNA Sequencing and Genotyping by fluorescent capillary electrophoresis; DNA Microarray Analysis by fluorescent tag/anti-tag hybridization; Real Time PCR by Taqman; ASO hybridization; Southern blot; Methylation Analysis; Allele-specific PCR

Laboratory for Molecular Medicine at HPCGG, Satellite Lab of MGH

Location:	Partners Research Building, Cambridge, MA
Website:	http://www.hpcgg.org/LMM/
Director:	Raju Kucherlapati, Ph.D.
Staff:	3 geneticists (2 ABMG-certified), lab manager, 6 technicians, genetic counselor, clinical testing assistant, billing assistant, additional affiliated support staff

Test Offerings:

Hypertrophic cardiomyopathy (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL2, MYL3, ACTC)
Danon Disease (LAMP2)
Noonan syndrome (PTPN11)
LEOPARD Syndrome (PTPN11, KRAS)
Costello Syndrome (HRAS)
CFC Syndrome (BRAF, KRAS)
Marfan syndrome (FBN1)
Pendred syndrome (PDS/SLC26A4)
Usher syndrome (MYO7A)
Hearing loss (Connexin 26, Connexin 30, MTTS1, MTNR1, COCH, MYO7A, PDS, POU3F4)
EGFR analysis for lung cancer drug response

Platforms:

DNA Sequencing, Genotyping, Identity analysis, MLPA (in development)

MGH Neurogenetics DNA Diagnostic Laboratory

Location:	usetts General Hospital, Boston, MA
Website:	http://www.dnalab.org
Director:	Katherine B. Sims, MD, Director Winnie Xin, Ph.D., Co-Director
Staff:	neurogeneticist, 2 geneticists, 4 technicians, lab coordinator

Test Offerings:

Dystonia (DYT1)

Myoclonus Dystonia (SGCE, M-D)
Rapid Onset Dystonia Parkinsonism (ATP1A3, RDP)
Dopa Responsive Dystonia (DRD, GTP cyclohydrolase)
Tyrosine Hydroylase deficient DRD (TH, under development)
Parkin (PARK2, under development)
Familial Amyotrophic Lateral Sclerosis (ALS1, AD-FALS, adult; SOD1)
ALS8 (VAPB, AD-Adult, under development)
ALS2 (ALSIN, AR-Juvenile; RanGEF, under development)
Hypokalemic Periodic Paralysis (CACNL1A3, HOPP)
Hypokalemic Periodic Paralysis (SCN4A, HOPP-2)
Hyperkalemic Periodic Paralysis (SCN4A, HYPP)
Hereditary Sensory Neuropathy (HSN1, SPTLC1)
Hereditary Sensory and Autonomic Neuropathy (HSN2, HSAN)
Erythromelalgia (SCN9A, under development)
Infantile Neuronal Ceroid Lipofuscinosis (INCL, CLN1)
Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL, CLN2)
Juvenile Neuronal Ceroid Lipofuscinosis (JNCL, CLN3, Batten disease)
Variant late infantile Neuronal Ceroid Lipofuscinosis (vLINCL, CLN6)
Progressive epilepsy with mental retardation (EPMR, CLN8)
Neurofibromatosis type 2 (NF2) [mutation screening; linkage]
Norrie disease (ND)
Tuberous Sclerosis (TSC1 and TSC2; known mutation and prenatal only)
Huntington disease (HD)
Friederichs Ataxia (FA)
Spinocerebellar ataxias: SCA1, SCA2, SCA6, SCA7
Machado-Joseph disease (MJD; SCA3)
Dentatorubral-pallidoluysian atrophy (DRPLA)
Paternity & Identity
Chromosome 1p/19q allele loss (anaplastic oligodendroglioma markers)

Platforms:

DNA Sequencing, Genotyping, SSCP, dHPLC, MLPA, Identity