In general, cascade testing starts with first-degree relatives: parents, brothers and sisters, and children. Each of these relatives shares about half of your DNA. If a first-degree relative has died or cannot be reached, testing moves to second-degree relatives: grandparents, aunts and uncles, nieces and nephews, and half-siblings. When a relative tests positive, their own first-degree relatives are then offered testing, and so on through the family.

Exactly who is at risk depends on how the condition is inherited.
• Autosomal dominant conditions One copy of the changed gene is enough to raise risk. Examples include BRCA1 and BRCA2, Lynch syndrome, and familial hypercholesterolemia. Each child of a carrier has a 1-in-2 chance of inheriting the change, and each brother or sister usually has a 1-in-2 chance too. One side of the family usually carries it, and testing parents can show which side.
• Autosomal recessive conditions A person is affected only if they inherit a changed copy from both parents. Examples include beta-thalassemia, sickle cell disease, and spinal muscular atrophy. Both parents of an affected child are usually carriers. Each brother or sister of an affected child has a 2-in-3 chance of being a carrier if they are unaffected. Aunts, uncles, and cousins on both sides may also be carriers. For these families, cascade testing is mainly about identifying carriers before they plan their own pregnancies, and testing their partners.
• X-linked conditions The changed gene sits on the X chromosome. Examples include Duchenne muscular dystrophy and Fragile X syndrome. Females in the mother’s line, such as sisters, maternal aunts, and female cousins, may be carriers and can have affected sons. Their carrier status matters for pregnancy planning and, in some conditions, for their own health.

A genetic counselor will usually draw a family tree with you. This shows exactly which relatives are at risk, how high their chance is, and which order makes the most sense, including which relatives to prioritize because they are of an age where screening or prevention would already apply.