Pathology

Disease

Population

Biology

Gene

Allele

Consanguinity

Genetics

Medicine

Environmental health

Journal of Rare Diseases

Purpose Consanguinity increases the likelihood of the inheritance of homozygous pathogenic alleles which may predispose to rare autosomal recessive disorders. Here we discuss the role of consanguinity in informing inherited disease with a focus on rare diseases. Methods We reviewed the literature concerning the impact of consanguinity on human diseases and chose examples to illustrate the most important themes. Results Consanguinity rates vary hugely between different populations influencing the prevalence of rare autosomal recessive diseases. Some founder genetic variants leading to human disease are specific for a single country, or a specific ethnic or geographic group while others are shared more widely. Inherited diseases of known molecular genetic etiology are characterized by their genotype and phenotype but many exhibit marked heterogeneity which may be population dependent. Increased rates of consanguinity are associated with rare autosomal recessive inherited diseases and can lead to more than one human genetic disease in affected individuals leading to complex and overlapping phenotypes. Next-generation sequencing strategies allow new insights into these cases. In contrast, the impact of consanguinity on malignancies and common multifactorial diseases is less predictable and needs further exploration. Conclusions High rates of consanguinity remain prevalent in certain populations and lead to an increased burden of rare autosomal recessive inherited diseases. Strategies to reduce consanguinity are needed to reduce these disease consequences and will require global improvements in education, social, and economic conditions.

The impact of consanguinity on human health and disease with an emphasis on rare diseases