Molecular genetics - genetic disorders

  1. 5-20 mL blood in EDTA tube; blood spot dried on neonatal screening card.

  2. Plucked hair roots or buccal smear dried on a glass slide.

  3. Tissue biopsy for fibroblast culture.

  4. Chorionic villus biopsy (from about week 11), amniotic fluid (from about week 15), fetal blood sample (from about week 18).

  5. Liver or muscle biopsy for some mitochondrial genetic disorders.


See Molecular genetics.


The use of genetic techniques is dependent on the availability of the technique (including an identified marker for the disease) and whether detection of the genetic abnormality will affect the management of the patient or the management of affected but asymptomatic relatives.

Direct diagnosis of the homozygous, hemizygous or heterozygous state is possible if the genetic abnormality has been defined. For some disorders, indirect diagnosis (family studies using one or more DNA polymorphisms closely linked to the abnormality) is available.

Reliable diagnosis is more difficult if several different mutations can give rise to the same phenotype or if only indirect diagnosis (family studies using DNA polymorphisms) is available.

Molecular genetic studies can also be used for the diagnosis of genetic predisposition to malignancy eg, patients with a family history of familial adenomatous polyposis.

The current availability of molecular genetic techniques for selected specific disorders is indicated in the Clinical problems listing. As the list of disorders for which testing is available is continually growing, more complete information is available from GeneTests or you should consult your nearest genetics laboratory. There is a list of laboratories in Australia and New Zealand performing specific genetic tests at the RCPA Catalogue of Genetic Tests and Laboratories.


Patients with an autosomal recessive disorder (eg, cystic fibrosis) may be homozygotes or compound heterozygotes (that is, with different pathogenic mutations on each chromosome). The specific mutation detected may predict disease severity.

The size of deletions, duplications or variable repeat regions (eg, fragile X syndrome, myotonic dystrophy) may allow prediction of likely severity.

Predictions based on family studies using DNA polymorphisms have a variable degree of uncertainty due to the possibility of chromosomal crossing over between the gene and the polymorphic marker (eg, in many families with haemophilia A, the mutation cannot be identified directly and family studies using DNA polymorphisms are required).

A negative result on a fetus or a potential carrier does not necessarily exclude the possibility.

Mitochondrial abnormalities may not be present in all copies of the genome (heteroplasmy); liver and skeletal muscle are the most reliable tissues for the detection of mitochondrial genetic disorders.

A set of polymorphic markers may be used to validate the fetal origin of cells from chorionic villi or amniotic fluid. They are also used to document the unusual occurrence of uniparental disomy, that is both chromosomes derived from the same parent eg, Prader Willi and Angelman syndromes.


Haines JL. ed. Current Protocols in Human Genetics. 2006. John Wiley and Sons.

Trent RJ. Clin Biochem Revs 1993; 14: 56-61.

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