Compound heterozygotes

Compound Heterozygotes

A compound heterozygote refers to an individual who has two different mutant alleles at a particular gene locus, one on each chromosome of a pair. This genetic condition is significant in the context of autosomal recessive disorders, where two copies of a mutant allele are necessary to express the phenotype associated with the disorder.

Genetic Basis

In a typical autosomal recessive disorder, an individual must inherit two copies of a mutant allele, one from each parent, to express the disease phenotype. In the case of compound heterozygosity, the individual inherits two different mutant alleles, each from one parent. These alleles are located at the same locus but have different mutations.

For example, in the case of cystic fibrosis, a common autosomal recessive disorder, a compound heterozygote might inherit the ΔF508 mutation from one parent and the G551D mutation from the other. Although these mutations are different, they both affect the same gene, the CFTR gene, leading to the disease phenotype.

Clinical Implications

Compound heterozygosity can complicate the diagnosis and treatment of genetic disorders. The presence of two different mutations can affect the severity of the disease, the response to treatment, and the overall prognosis. For instance, in phenylketonuria (PKU), different mutations can lead to varying levels of enzyme activity, influencing dietary management and treatment strategies.

Diagnosis

The diagnosis of compound heterozygosity typically involves genetic testing, such as DNA sequencing or genotyping, to identify the specific mutations present in the individual's genome. This information is crucial for genetic counseling, as it helps predict the risk of passing the disorder to offspring and informs family planning decisions.

Examples of Disorders

Several genetic disorders can result from compound heterozygosity, including:

• Cystic fibrosis
• Phenylketonuria
• Tay-Sachs disease
• Sickle cell disease (in combination with other hemoglobinopathies)

Also see

• Autosomal recessive inheritance
• Genetic mutation
• Homozygote
• Heterozygote
• Genetic counseling