AN ALU ELEMENT RETROPOSITION IN 2 FAMILIES WITH HUNTINGTON DISEASE DEFINES A NEW ACTIVE ALU SUBFAMILY

Alu repetitive elements represent the most common short interspersed e lements (SINEs) found in primates, with an estimated 500,000 members i n the haploid human genome. Considerable evidence has accumulated that these elements have dispersed in the genome by active transcription f ollowed by retroposition, and that this process is ongoing. Sequence v ariation between the individual elements has lead to the hierarchical classification of Alu repeats into families and subfamilies. Young sub families that are still being actively transposed are of considerable interest, and the identification of one such subfamily (designated 'PV ') has lead to the hypothesis that the most recent retroposition event s are due to a single master Alu source gene. In the course of our sea rch for the gene causing Huntington disease, we have detected an Alu r etroposition event in two families. Sequence analysis demonstrates tha t this Alu element is not a member of the PV subfamily, but is similar to 5 other Alu elements in the GenBank database. Together, these Alu elements, all of which contain a 7 base-pair internal duplication, def ine a distinct subfamily, designated as the Sb2 subfamily, providing e vidence for a second actively retroposing Alu source gene. These data provide support for multiple source genes for Alu retroposition in the human genome.