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The electronic form of this document may be cited in the following style:
Human Genome Program, U.S. Department of Energy, DOE Human Genome Program Contractor-Grantee Workshop IV, 1994.

Abstracts scanned from text submitted for November 1994 DOE Human Genome Program Contractor-Grantee Workshop. Inaccuracies have not been corrected.

Alu Repeats: Source for the Genesis of Simple Sequence Repeats

Santosh S. Arcot[1], Hernan Bazan[2], Prescott L. Deininger[2] and Mark A. Batzer[1]
[1]Human Genome Center, L-452, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550. [2]Department of Biochemistry, Louisiana State University Medical Center, 1901 Perdido St., New Orleans, LA 70112.

Repeated DNA sequences comprise almost 50% of the human genome. These sequences may be divided into those that are tandemly arrayed and those which are interspersed. Alu sequences, the most common form of Short INterspersed Elements (SINEs) found within the human genome, are present at a copy number in excess of 500,000/haploid genome. Tandemly arrayed repetitive sequences may be divided into two classes based upon the size of each repeat unit and are generally referred to as Simple Sequence Repeats (SSRs). Minisatellites are composed of repeat units that are greater than 9 bp each while microsatellites have basic repeat units of 9 bp or less. The size and high degree of heterozygosity of microsatellites and minisatellites has made them one of the most important DNA based markers for genetic linkage mapping and forensic identity testing. Alu repeats integrate into AT rich regions of the genome, are flanked by short intact direct repeats (formed from the preintegration site) and also contain a characteristic 3' oligo-dA rich tail. In recent years, a number of SSRs have been found adjacent to the 3' end of Alu family members. The association between SSRs and Alu sequences may occur through the insertion of one repeated DNA sequence (Alu element) near a SSR, or be a direct result of mutations which occur in the 3' oligo-dA rich tail after the insertion of the Alu SINE followed by the expansion/contraction of these regions.

In order to resolve between these two models for the association of Alu sequences and SSRs we performed a DNA sequence analysis of several recently inserted human-specific (HS) Alu repeats with SSRs located in the 3' flanking region from both human and non-human primate (chimpanzee) genomes. DNA sequence analysis of the chimpanzee orthologues demonstrated that they did not contain a SSR. These data indicate that the SSRs adjacent to these HS Alu sequences arose as a result of mutations within the oligo-dA rich tails of the Alu repeats. Therefore, the 500,000 Alu repeats dispersed throughout the human genome represent a novel source for the generation of new SSRs.

This work was supported in part by grants from the U.S. Department of Energy (LDRD 94-LW-103) to M.A.B. and National Institutes of Health (ROl HG 00770) to P.L.D and by Lawrence Livermore National Laboratory under the auspices of the U.S. Department of Energy under contract no.W-7405-ENG-48.