A NOVEL ZINC FINGER CDNA WITH A POLYMORPHIC PENTANUCLEOTIDE REPEAT (ATTTT)(N) MAPS ON HUMAN CHROMOSOME-19P

To isolate genes that contain zinc finger motifs, a human brain cDNA library was screened with an oligonucleotide complementary to the conserved "linker" sequence between adjacent zinc fingers. The insert of one positive clone of 1226 nucleotides contained a novel open reading frame (ZNF121) with 9 zinc finger motifs; in addition, 10 repeats of the pentanucleotide sequence (ATTTT) were found 223 nucleotides after a stop codon and were followed by an Alu repeat. A sequence-tagged site of 172 nucleotides containing this repeat was defined by two oligonucleotide primers, mapped to chromosome 19 using commercially available mapping panels of hybrid cell lines, and designated D19S204. The pentanucleotide repeat was polymorphic in the members of CEPH families, with 7 alleles ranging in size from 147 to 197 nucleotides. The observed heterozygosity in unrelated CEPH parents was 58% (46 of 79). Genotypes from 34 informative CEPH families were used to perform linkage analyses with other polymorphic markers contained in the CEPH V5 database; strong linkage was found with markers on the short arm of chromosome 19. The zinc finger cDNA described here maps in an area where other zinc finger sequences and multiple cosmid clones containing zinc fingers have been previously localized. The ease of scoring these polymorphic alleles indicates that pentanucleotide repeat polymorphisms may be a particularly useful class of DNA markers for linkage studies. © 1993 by Academic Press, Inc.