HUMAN MEGASATELLITE DNA RS447 - COPY-NUMBER POLYMORPHISMS AND INTERSPECIES CONSERVATION

We previously isolated a novel 4.7-kb RS447 sequence, which tandemly r epeated approximately 50-70 copies and resided on human chromosome 4p1 5 (M. Kogi et al, 1997, Genomics 42: 278-283). Another tandem array (o r arrays) of several RS447 copies was hereby identified on the distal part of chromosome 8p. To analyze copy-number polymorphisms of the RS4 47 repeats, genomic DNA samples of eight nonkindred Japanese were subj ected to pulsed-held gel electrophoresis. The copy numbers of the RS44 7 tandem arrays on 4p15 varied drastically from allele to allele and r anged from approximately 34 to 94 copies. All eight Japanese subjects were apparently heterozygous for the RS447 copy number, and 12 copy-nu mber-different alleles have been at least clearly distinguished. The R S447 tandem repeats were thus found to be hypervariable and highly pol ymorphic in a human population. The RS447 sequences, however, do not a ppear to be either ''selfish'' or ''junk'' DNA. The unit size and sequ ence of RS447 were found to be very similar between members in the hum an genome. The unit size of 4746 bp comprises a putative open reading frame of 1590 bp. The RS447 sequence was well conserved in all the tes ted mammalian species. The head-to-tail tandem repetitive structure in the RS447 homologs was also confirmed in those species. The RS447 seq uence is, therefore, considered to consist of a new class of tandemly repeated satellite DNA elements in the mammalian genome, which may thu s be called ''megasatellite DNA'' (C) 1998 Academic Press.