Consanguinity

Understanding Consanguineous Matings

The chance that both parents are carriers of a mutant allele Opens in new window at the same locus is increased substantially if the parents are related and could each have inherited the mutant allele Opens in new window from a single common ancestor, is a situation known as consanguinity.

Consanguinity of the parents of a patient with a genetic disorder is strong evidence (although not proof) for the autosomal recessive inheritance Opens in new window of that condition.

The genetic risk to the offspring of marriages between related people is not as great as is sometimes imagined.

For marriages between first cousins, the absolute risks of abnormal offspring, including not only known autosomal recessive diseases but also stillbirth, neonatal death, and congenital malformations, is 3% to 5%, about double the overall background risk of 2% to 3% for offspring born to any unrelated couple.

Consanguinity at the level of third cousins or more remote relationships is not considered to be genetically significant, and the increased risk of abnormal is negligible in such cases.

Although the incidence of cousin marriage is low (~1 to 10 per 1000) in many populations in Western societies today, it remains relatively common in some ethnic groups, for example, in families from rural areas of the Indian subcontinent, in other parts of Asia, and in the Middle East, where between 20% and 60% of all marriages are between cousins.

In general, however, the frequency of first-cousin marriages, and consanguinity in general, is declining in many traditional societies. Consanguinity is not the most common explanation for an autosomal recessive trait Opens in new window.

The mating of unrelated persons, each of whom happens by chance to be a carrier, accounts for most cases of autosomal recessive disease, particularly if a recessive trait has a high frequency in the population.

Thus, most affected persons with a relatively common disorder, such as cystic fibrosis (CF) Opens in new window, are not the result of consanguinity, because the mutant allele is so common in the general population. However, consanguinity is more frequently found in the background of patients with very rare conditions. For example, in xeroderma pigmentosum Opens in new window, a very rare autosomal recessive condition of DNA repair, more than 20% of cases occur among offspring of marriages between first cousins.

The Measurement of Consanguinity

The measurement of consanguinity is relevant in medical genetics because the risk of a child’s being homozygous for a rare recessive allele is proportional to how related the parents are. Some types of consanguineous mating carry an increased risk.

Consanguinity is measured by the coefficient of inbreeding (F), the probability that a homozygote has received both alleles at a locus from the same ancestral source; it is also the proportion of loci at which a person is homozygous for an allele from the same ancestral source, a situation referred to as identity by descent.

Table X-1 shows the coefficients of inbreeding for the offspring of a number of consanguineous matings. If a person is inbred through more than one line of descent, the separate coefficients are summed to find his or her total coefficient of inbreeding.