Review of SCOBEC laboratories collaboration: 5 years Rebecca Treacy1, Rachel Butler2, Maggie William

1
Review of SCOBEC laboratories collaboration 5
yearsRebecca Treacy1, Rachel Butler2, Maggie
Williams3, Sian Ellard4, Anneke Seller5, Sarah
Warburton6, Trudi Mann7, John Harvey8, Jo
Whittaker1 1. Molecular Genetics Laboratory,
Addenbrookes Hospital, Cambridge, 2. Molecular
Genetics Laboratory, University Hospital Wales,
Cardiff, 3. Bristol Genetics Laboratory, North
Bristol NHS Trust, Bristol, 4. Department of
Molecular Genetics, Royal Devon Exeter NHS
Foundation Trust, Exeter, 5. Oxford Regional
Genetics Laboratory, Oxford Radcliffe Hospitals
NHS Trust, 6. National Training Co-ordinator for
Clinical Molecular Genetics, c/o Birmingham
Womens Hospital, 7.Delivery Manager, South West
Strategic Health Authority, 8. Molecular Genetics
Laboratory, Salisbury District Hospital
Background The publication of the governments
White Paper Our inheritance, our future
realising the potential of genetics in the NHS
in June 2003 led to the collaboration of six
molecular genetics laboratories (Salisbury,
Cardiff, Oxford, Bristol, Exeter and Cambridge)
and the formation of SCOBEC. The initial remit
of this collaboration was to facilitate
implementation of the White paper bid in the
participant laboratories and progress towards
meeting the government reporting time targets for
genetic analysis. Since the initial test
rationalisation process, the scope of the SCOBEC
collaboration has grown.
Rationalisation of medium throughput tests Test
Number of labs offering
test Pre
Post AS/PWS 5 3 CMT1a 5
3 FRDA 5
3 SCA 5
2 DM1 5 4 MEN2 5
2 Rett (MECP2) 3 2 SBMA
6 1 DRPLA
4 1 Mitochondrial 3
1 FAP 4 2 MutY
3 2
Reporting time data from 2005-2008 Not
es (1) Historical backlog samples skew the 40
days data since they cannot easily be excluded
from the data but will not be reported within the
target times (2) MLPA only tests are counted
within the 10 day target from Qtr 1 2007/2008
(previously 40 days - amendment by the CMGS) (3)
Neonatal cystic fibrosis screening target
reporting times are 3 days for Wales and 4 days
in England. The Cardiff data includes these tests
within the 3 day target until Qtr 2 2007/2008,
and then within the 10 day target for consistency
with the other SCOBEC labs  (4) 2007-2008 Q3
Cardiff data includes clearance of NF1and ARX
backlogs (5) Data missing one lab 2005-2006,
one lab Q3 07-08
Screening of BRCA1 2 elimination of patient
sample backlogs Salisbury HT facility 1280
outstanding samples received prior to May 2006
tested between April 2006 and May 2007 (2129
samples now been tested to date) Results 15
pathogenic mutations, 15.8 unclassified
variants Oxford, Cambridge Cardiff screened 924
samples 17 pathogenic mutations, 5
unclassified variants Majority of referrals
require screening of 79 fragments MLPA

• Peer review
• Laboratories undertook a peer review to discuss
  laboratory process for
• User Information, sample reception, DNA/RNA
  extraction, PCR, Mutation screening by
  sequencing, Predictive/prenatal tests,
  Interpretation of novel variants, Reports,
  Reporting times, Exported samples, Data
  archiving, Lab management issues
• Main points from review
• Use of software rather than manual checking of
  sequence traces, reduces labour costs and
  improves TATs. Robust QC and sensitivity data
  required
• Limited numbers of senior scientists for
  checking should be linked to expertise in test
  area and nature of test rather than staff
  grade/seniority
• Changing/increasing role of genetic
  technologists reduces staffing costs move to
  process based rather than test based organisation
  of work flow
• Single directional rather than bi-directional
  sequencing for mutation screening will reduce
  test consumables costs requires optimisation of
  primer sets (initial staff and reagent cost)
• Lack of information on test request form
  requires time-consuming clarification standard
  template and response to requestor
• Sample reception has duplication of effort with
  separate disciplines common functional area and
  integration
• Implementation of LIMS software to manage
  throughput
• Effective gate-keeping arrangements for tests
  requested by non-clinical geneticists needs
  equitable arrangements for funding gatekeeping
• Duplicate blood sampling for presymptomatic
  testing not necessary

Introduction of new gene tests Renal PKD2
(ADPKD), CLCNKB (Bartter syndrome), SLC12A3
(Gitelman syndrome), ACTN4 (FSGS), SLC4A1 (dRTA),
CYP11B1/2 (GRA), SCNN1B/1G (Liddle), UMOD
(FJHN/MCKD2), PKHD1 (ARPKD) Neurological XLMR
Tau, PGRN (FTDP), LIS1 (Lissencephaly), CDKL5
(X-linked infantile spasms), SLC16A2 (AHDS),
ARX Biochemical genetics HFE, INSR (RMS, DS),
ALB (FDH), ALDB (HFI), THRB, MCAD, CF newborn
screening Eye PAX6-related Anophthalmia,
SOX2-related, HOXA1, ROBO3, SALL4,
KIF21A Cancer MUTYH, HNPCC (MSH6) full HT
screening for breast cancer (BRCA 1 and 2), SMAD4
BMPR1A (JPS) Neuromuscular SPTLC1 (HSN1),
EGR2 (Severe demyelinating PN), periaxin (severe
demyelinating PN), NEFL (Variable type 1 or type
2 PN), FSHD - 4QA/B polymorphism testing, PROMM
(DM2) Cardiac MYH7, MYBPC3, TNNT2, TNNI3
(HCM/DCM), KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2
(LQT) Myasthenic CHRNB1, CHRND, RAPSN, COLQ,
CHAT, DOK-7 Endocrine ABCC8, KCNJ11, GLUD1,
GCK, SCHAD (hyperinsulinism), KCNJ11, ABCC8, INS,
GCK, PTF1A, GLIS3, FOXP3, EIF2AK3, SLC19A2
(neonatal diabetes), P27KIP1 (MEN1), DMP1/SLC34A3
(hypophosphataemic rickets), GALNT3 (tumour
calcinosis), AIP (familial pituitary tumours),
HRPT2, AIRE, GATA3, GCM2, PTH Craniofacial
EFNB1, MSX2, ALX4, POR, FGF10 Skeletal ARSE,
DHAPAT, AGPS (chondrodysplasia punctata), MESP2
(Spondylocostal dysostosis), GLI3, HOXD13, ROR2,
TCOF1 Mitochondrial mt depletion, POLG, PEO1,
ANT1 Prognostic Oncology MGMT methylation
testing for glioblastoma, Polycythaemia (JAK2),
AML (NPM1 and FLT3) Other CFTR sequencing/MLPA,
NOTCH2 (Alagille), CCHS polyalanine expansion and
sequencing, PWS/AS MS-MLPA, FV and prothrombin,
TB genotyping, EDAR
Training initiatives 1) Training days Genetic
technologists, Triplet repeat disorders
(Scientists), CMGS training officers, Cancers
(Scientist), Registration preparation day,
Imprinting Neuromuscular disorders
(Scientists), Technical implementation
Validation (high throughput sequencing MLPA) 2)
SCOBEC training manual for scientists 3)
Assessment and support for 23 trainee clinical
scientist 4) Shared learning during validation
implementation of new equipment (e.g. automated
DNA extraction equipment), including process
redesign and troubleshooting

• Summary of SCOBEC group leading change
• single direction sequencing sufficient for
  mutation screening (at least one of other UK lab
  is now also doing this)
• interpretation of White Paper reporting times
  ongoing work to investigate feasibility of
  meeting 10 day reporting time category
• project on sensitivity of Mutation Surveyor
  software
• 3/7 UK labs in Phase I of STARLIMS development
  are from SCOBEC
• Test costings project to provide information for
  National Tariff

• Financial initiatives
• Comparison of test costs and rationalisation of
  tests has lead to standardisation of some
  costings
• Review of consumables procurement and costings