Genomics in general practice

Disease specific topics



General practitioners (GPs) play an important role in identifying potential carriers Recessive genetic conditions such as cystic fibrosis (CF) occur when a person inherits a particular genetic variant from each parent. A carrier is an individual who only has one copy of the gene variant and generally does not have symptoms, but can pass the variant to their children. Some conditions are due to a pathogenic variant in a gene on the X chromosome (X-linked inheritance). Typically, these conditions affect more males (who have the sex chromosomes XY) than females (who have the sex chromosomes XX). A woman who is a carrier of an X-linked condition has the variation on one of her X chromosomes, which she can pass on to her children. However, if the biological male has a pathogenic variant in an X chromosome gene, he will not pass it to his sons, but will pass it to all of his daughters. of haemoglobinopathies. They also play an important role in identifying couples who are at risk of having a child with a haemoglobinopathy. 

Carrier screening Carrier screening is a test to determine whether an individual carries a genetic variant that does not generally affect that individual’s health, but increases his or her chance of having children with the condition in question. The outcome of such testing can influence future reproductive decisions. Carrier screening is performed on individuals who are not necessarily known to be at increased risk for a particular genetic condition. Screening tests can be conducted on individuals from specific groups such as those from a common ethnic background (eg: screening for Tay-Sachs disease carrier status in the Ashkenazi Jewish community) or entire populations. should be offered to all couples who are planning pregnancy or in the first trimester of pregnancy. 

To enable timely reproductive choices during early pregnancy, carrier screening should be offered to couples at the same time (ie both partners should be tested as early as possible).

What do I need to know?

The term ‘haemoglobinopathies’ covers a range of conditions with an autosomal recessive inheritance Autosomal recessive conditions affect either sex, and often occur in the absence of any family history. Recessive conditions or traits appear when an individual inherits two copies of pathogenic variants in the same gene (one from each parent). Parents of a child with an autosomal recessive condition are usually asymptomatic carriers. The affected child has two copies of the particular gene change. The recurrence risk of autosomal recessive conditions is one in four for each pregnancy. Wide variability in clinical expression is common in many autosomal recessive conditions. Autosomal recessive conditions are more common when the parents are consanguineous. pattern that affect haemoglobin, including α-thalassaemia and β-thalassaemia, sickle cell disease and other abnormal haemoglobins, such as haemoglobin E (HbE).

Individuals with thalassaemia produce insufficient haemoglobin, while those with sickle cell disease produce structurally abnormal haemoglobin. The clinical implications range from mild through to death in utero.

Collectively, haemoglobinopathies are the most common single gene disorders in humans, and around 7% of the world’s population are carriers. Haemoglobinopathies are becoming more prevalent in Australia given immigration from endemic regions.

While carriers are often asymptomatic, carrier status becomes clinically significant in women who are carriers and planning a pregnancy, where the biological male partner is also a carrier.1 Screening for haemoglobinopathies is not part of newborn screening programs in Australia.

Carrier screening should be discussed as part of pre-pregnancy and prenatal care with all individuals: Those at particular risk are listed below but these should not be relied upon to identify carriers of a haemoglobinopathy:

  • Those with family history of anaemia or haemoglobinopathy 
  • Those from the following ethnic backgrounds (have increased carrier frequency)
    • southern European
    • African
    • Middle Eastern
    • Chinese
    • Indian subcontinent
    • central and south-east Asian
    • Pacific Islander
    • New Zealand Maori
    • South American
    • Caribbean
    • some northern Western Australian and Northern Territory Aboriginal and Torres Strait Islander communities
  • Those with a mean corpuscular volume (MCV) <80 fL or mean corpuscular haemoglobin (MCH) <27 pg.

Genetic testing

Order a haemoglobinopathy screen to include:

  • full blood examination (FBE) for MCV and MCH
  • ferritin to exclude iron deficiency
  • haemoglobin electrophoresis
  • DNA testing if indicated (Table 1).

There is an urgency to test the biological male partner concurrently when an at-risk woman who is a carrier is pregnant. DNA testing is required when α-thalassaemia cannot be excluded and the partner is a known carrier of two-gene deletion α-thalassaemia (Table 1).

Table 1. Interpretation of haemoglobinopathy carrier testing results

MCH (pg)/MCV (fL)


Haemoglobin electrophoresis


MCH <27 and/or

MCV <80


HbA2 increased

β-thalassaemia carrier


HbA2 normal

HbH present

α-thalassaemia carrier


HbA2 normal

HbH high

Possible HbH α-thalassaemia


HbA2 normal

HbE present

HbE carrier or homozygote



Possible α-thalassaemia carrier; DNA testing indicated




Iron deficiency


Thalassaemia may co-exist (treat iron deficiency then retest)


If woman is pregnant, seek advice about further tests

MCH ≥27 and/or MCV ≥80



Thalassaemia unlikely but one-gene deletion α-thalassaemia not excluded; DNA testing indicated only if partner is carrier of 2-gene deletion α-thalassaemia



HbS present

Carrier for sickle cell disease




Reduced iron stores or iron deficiency, thalassaemia unlikely but one-gene deletion α-thalassaemia not excluded. Treat iron deficiency then retest

HbA2, normal variant of haemoglobin with two α-globin and two β-globin chains; HbE, abnormal variant of haemoglobin, due to abnormal β-globin; HbH, abnormal variant of haemoglobin, due to excess β-globin chains relative to β-globin chains, a type of α-thalassaemia; HbS, abnormal variant of haemoglobin, due to abnormal β-globin; MCH, mean corpuscular haemoglobin; MCV, mean corpuscular volume

Adapted from Metcalfe SA, Barlow-Stewart K, Campbell J, Emery J. Genetics and blood – Haemoglobinopathies and clotting disorders. Aust Fam Physician 2007;36(10):812–19.

When should I refer?

Urgent referral should be made to genetics and/or haematology services when carrier couples are identified during pregnancy in order to allow for timely reproductive decisions, or when a pregnant woman is identified as a carrier and testing of the biological male partner has not been done.

Urgent referral should be made to haematology services if a pregnant woman is found to have abnormal variant of haemoglobin (HbH) α-thalassaemia.

Other considerations

Do not assume low MCV or MCH is due to iron deficiency alone, especially in at-risk individuals. If the patient is not pregnant, treat for the iron deficiency then retest. If MCV or MCH remain low, the individual is possibly a carrier of a haemoglobinopathy. If the patient is pregnant, DNA testing for α-thalassaemia is indicated.

A woman only needs to have haemoglobinopathy screening once – if MCV or MCH is low but was previously normal, it is most likely due to iron deficiency.

Further reading

  • Tan YL, Kidson-Gerber G. Antenatal haemoglobinopathy screening in Australia. Med J Aust 2016;204(6):226–30.
  • The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Genetic carrier screening. 2019. Accessed 1 March 2022.
  • The Royal Australian College of General Practitioners Guidelines for preventive activities in general practice. 9th edn. Melbourne: RACGP, 2016. [Accessed 6 September 2022].
  • Norita Hussein , Lidewij Henneman , Joe Kai, Nadeem Qureshi. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease. Cochrane Database Syst Rev. 2021 Oct 11;10:CD010849. doi: 10.1002/14651858.CD010849.pub4.

Resource for general practitioners

Resources for patients

This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log