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

Cystic Fibrosis – provided by CF Network

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 mutations 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; Mutation screening of the CFTR gene

Molecular Haematology – Module 01

This module is a qualitative assessment of laboratories in the detection of Factor V Leiden, Methylenetetrahydrofolate reductase and Prothrombin mutations.

Frequency / Number of samples

1 survey / 8 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; Mutation screening of the F2, F5 and MTHFR genes

Molecular Haematology – Module 02

This module is a qualitative assessment of laboratories in the detection of hereditary hemochromatosis mutations.

Frequency / Number of samples

1 survey / 8 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; Mutation screening of the HFE gene

Molecular Haematology – Module 03 (Qualitative)

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

Molecular Haematology – Module 03 (Quantitative)

This module is a quantitative assessment of laboratories in the measurement of % BCR/ABL in Chronic Myeloid Leukaemia (CML) and Acute Lymphoblastic Leukaemia (ALL). Lyophilised cells are supplied for RNA extraction.

Frequency / Number of samples

1 survey / 5 samples per survey (Lyophilised cell lines)

Tests

Molecular genetic analysis; RNA extraction; Quantitative PCR testing

Molecular Haematology – Module 04

This module is a qualitative assessment of laboratories 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

Molecular Haematology – Module 05

This module is a qualitative assessment of laboratories 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

Molecular Haematology – Module 06

This module is a qualitative assessment of laboratories in the detection of ?-thalassemia (HBA1/HBA2) and/or ?-thalassemia (HBB) gene mutations.

Frequency / Number of samples

1 survey / 4 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; Mutation screening of the HBA1/HBA2 and HBB genes

Molecular Haematology – Module 07

This module is a qualitative assessment of laboratories in the detection of Janus Kinase 2 (JAK2) gene mutations.

Frequency / Number of samples

1 survey / 8 samples per survey (DNA in TE buffer)

Tests

Molecular genetic analysis; Mutation screening of the JAK2 gene

Molecular Haematology – Module 08

This module is a qualitative assessment of laboratories in the detection of translocations in the Promyelocytic Leukaemia/Retinoic Acid Receptor Alpha (PML-RAR?) gene.

Frequency / Number of samples

1 survey / 3 samples per survey (Lyophilised RNA)

Tests

Molecular genetic analysis to determine PML-RAR? gene translocation status

Molecular Haematology – Module 09

This module is a quantitative assessment of laboratories in the identification of internal tandem duplication mutations 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; Mutation screening of the FLT3 gene

Molecular Haematology – Module 10

This module is a quantitative assessment of laboratories in the identification of nucleophosmin 1 (NPM1) gene mutations.

Frequency / Number of samples

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

Tests

Molecular genetic analysis; Mutation screening of the NPM1 gene