Molecular Genetics

The two main branches of genetic pathology are:

Biochemical Genetics which includes,

  • Population-based screening for inborn errors of metabolism by enzyme, protein and metabolite assays; and, diagnostic screening for inborn errors of metabolism in symptomatic patients by analysis of metabolites such as organic acids and amino acids;
  • Diagnostic assays for specific disorders by analysis of specific analytes in body fluids, enzymatic studies, or DNA studies of specific genes;
  • Predictive assays in unaffected relatives (or a fetus) to determine the risk of developing the disorder known to be present in the family;
  • Pedigree analysis and diagnostic assessment of segregation in kindreds of disease-causing mutations or genomic regions
  • Monitoring the biochemical status of patients for long-term care or to guide acute care in metabolic crises.

Medical Genomics which includes,

  • Diagnostic detection and interpretation of genomic/ epigenomic variants in symptomatic patients (children, adults, fetuses);
  • Pedigree analysis and diagnostic assessment of segregation in kindreds of disease-causing mutations or genomic regions;
  • Diagnostic detection and interpretation of mosaic genomic variants, e.g. in cancer, pregnancy, and inherited diseases (e.g. tumour material; constitutional mosaicism; fetal DNA in maternal blood, circulating tumour DNA etc.) and quantitative assessment of mosaic genomic variants;
  • Predictive/presymptomatic assays in unaffected relatives (or a fetus) to determine the risk of inheritance of a familial disorder;
  • Population-based screening for genomic abnormalities (antenatal and newborn screening programs);
  • Application of probability, statistics, bioinformatics databases, and other aspects of computer science relevant to the practice of genetic pathology

CF Network Cystic Fibrosis

This is an external quality assessment scheme for cystic fibrosis provided by the European Cystic Fibrosis Network (CF Network). Purified DNA samples accompanied by mock clinical cases will be provided to registered laboratories to test for the presence of CFTR variants using routine protocols. Laboratories are required to submit written reports and raw data via eletronic upload to the CF Network website.

Frequency / Number of samples

1 survey / 3 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; variant screening of the CFTR gene

RCPAQAP ALK Translocation in NSCLC

This module qualitatively assesses laboratory performance in the detection, reporting and interpretation of Anaplastic Lymphoma Kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) using either fluorescence in-situ hybridisation (FISH), immunohistochemistry (IHC) or other routine molecular methods.

Frequency / Number of samples

1 survey / 3 samples per survey (Patient-derived FFPE tissue)

Tests

Molecular genetic analysis to determine ALK gene rearrangement status

RCPAQAP BCR-ABL Qualitative Testing

This module is a qualitative assessment of laboratories in the identification of BCR/ABL translocations in Chronic Myeloid Leukaemia (CML) and Acute Lymphoblastic Leukaemia (ALL).

Frequency / Number of samples

1 survey / 3 samples per survey (Lyophilised RNA)

Tests

Molecular genetic analysis to determine BCR/ABL translocations status

RCPAQAP Chimerism Analysis

This module qualitatively and quantitatively assesses laboratory performance in the evaluation and reporting of donor versus recipient cells in post-transplant peripheral blood or bone marrow specimens.

Frequency / Number of samples

1 survey / 5 samples per survey (DNA in TE buffer)

Tests

Chimerism analysis

RCPAQAP Coeliac Disease HLA Genotyping

This module qualitatively assesses laboratory performance in the detection, reporting and interpretation of the HLA-DQ2/DQ8 antigens and associated HLA-DQA1 and HLA-DQB1 gene haplotypes.

Frequency / Number of samples

1 survey / 5 samples per survey (DNA in TE buffer)

Tests

HLA genotyping

RCPAQAP FLT3 ITD

This module qualitatively and quantitatively assesses laboratory performance in the identification of internal tandem duplication of the fms related tyrosine kinase 3 (FLT3) gene.

Frequency / Number of samples

1 survey / 3 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; variant screening of the FLT3 gene

RCPAQAP FMR1 Related Disorders

This module qualitatively assesses laboratory performance in the detection and interpretation of CGG expansions in various FMR1-related disorders.

Frequency / Number of samples

1 survey / 5 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis to detect and measure CGG expansions in the FMR1 gene

RCPAQAP Hereditary Haemochromatosis (HFE)

This module qualitatively assesses laboratory performance in the detection of hereditary hemochromatosis variants (p.Cys282Tyr, p.His63Asp, p.Ser65Cys).

Frequency / Number of samples

2 surveys / 4 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; variant screening of the HFE gene

RCPAQAP Human Leukocyte Antigen B*57

This module assesses laboratory performance in the detection, reporting and interpretation of the HLA-B*5107 allele.

Frequency / Number of samples

4 surveys / 3 samples per survey (DNA in TE buffer)

Tests

HLA genotyping

RCPAQAP IDH Mutation Analysis in Glioma

This is a sample exchange program where participating laboratories provide specimens to RCPAQAP, which will be de-identified, re-labelled and distributed. This program assesses laboratory performance in the detection of isocitrate dehydrogenase (IDH) 1 and 2 gene variants in glioma.

Frequency / Number of samples

1 survey / 3 samples per survey (Patient-derived FFPE tissue)

Tests

Molecular genetic analysis; FFPE DNA extraction; Mutation screening of the IDH1 and IDH2 genes

RCPAQAP IDH Variant Analysis in AML (IDH1, IDH2)

This module qualitatively assesses laboratory performance in the detection of isocitrate dehydrogenase (IDH) 1 and 2 gene variants in Acute Myeloid Leukaemia (AML).

Frequency / Number of samples

1 survey / 3 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; variant screening of the IDH1 and IDH2 genes

RCPAQAP Immunogenotyping (IgH,TCR)

This module qualitatively assesses laboratory performance in the detection of immunoglobulin heavy chain and T-cell receptor gene rearrangements.

Frequency / Number of samples

1 survey / 5 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis to determine IGH and TCR gene rearrangement status