MAPPING HUMAN TELOMERE REGIONS WITH YAC AND P1 CLONES - CHROMOSOME-SPECIFIC MARKERS FOR 27 TELOMERES INCLUDING 149 STSS AND 24 POLYMORPHISMS FOR 14 PROTERMINAL REGIONS

A YAC library enriched for telomere clones was constructed and screene d for the human telomere-specific repeat sequence (TTAGGG). Altogether 196 TYAC library clones were studied: 189 new TYAC clones were isolat ed, 149 STSs were developed for 132 different TYACs, and 39 P1 clones were identified using 19 STSs from 16 of the TYACs. A combination of m apping methods including fluorescence in situ hybridization, somatic c ell hybrid panels, clamped homogeneous electric fields, meiotic linkag e, and BLASTN sequence analysis was utilized to characterize the resou rce. Forty-five of the TYACs map to 31 specific telomere regions. Twen ty-four linkage markers were developed and mapped within 14 protermina l regions (12 telomeres and 2 terminal bands). The polymorphic markers include 12 microsatellites for 10 telomeres (1q, 2p, 6q, 7q, 10p, 10q , 13q, 14q, 18p, 22q) and the terminal bands of 11q and 12p. Twelve RF LP markers were identified and meiotically mapped to the telomeres of 2q, 7q, 8p, and 14q. Chromosome specific STSs for 27 telomeres were id entified from the 196 TYACs. More than 30,000 nucleotides derived from the TYAC vector-insert junction regions or from regions flanking TYAC microsatellites were compared to reported sequences using BLASTN. In addition to identifying homology with previously reported telomere seq uences and human repeat elements, gene sequences and a number of ESTs were found to be highly homologous to the TYAC sequences. These genes include human coagulation factor V (F5), Wee1 protein tyrosine kinase (WEE1), neurotropic protein tyrosine kinase type 2 (NTRK2), glutathion e S-transferase (GST1), and beta tubulin (TUBB). The TYAC/P1 resource, derivative STSs, and polymorphisms constitute an enabling resource to further studies of telomere structure and function and a means for ph ysical and genetic map integration and closure. (C) 1996 Academic Pres s, Inc.