Molecular genetics and anthropology: Genes, races and diseases

RESUMO

Advances of molecular genetics which have helped to characterize the genetic features of the Brazilian population and the relationship between ethnicity and disease are summarized. We discuss our contributions to: a) DNA polymorphisms in Amazonian Indians; b) origin and heterogeneity of the sickle cell anemia gene; c) mutations of the LDL-receptor gene; d) mutations which cause hemophilias. The beta-globin gene haplotypes of Indians present a close similarity with Asian populations, which strengthens the argument for an Asiatic origin of the native populations of America. Sickle cell anemia mutation occurs with at least five different haplotypes, which originated in distinct geographic regions of Africa and Asia. The Bantu haplotype is the most frequent haplotype in Brazil, while the Benin haplotype predominates in the USA and Jamaica, as a consequence of different patterns of slave traffic to North and South Americas. This heterogeneity may be responsible for differences in the clinical behavior of the disease and other features among black populations of the Americas. In 50 per cent of families with familial hypercholesterolemia, the disease was caused by the Lebanese allele, a nonsense mutation of the LDL-r gene, always observed in families of Arab origin. Thus, this mutation is probably the most common cause of familial hypercholesterolemia in Brazil. In contrast, the mutations responsible for hemophilias A and B are heterogeneous, and show no particular association with racial groups. Recently, five hemophilia mutations were characterized in our laboratory, including previously unreported deletions and point mutations of coagulation factors VIII and IX.