BAC AND PAC CONTIGS COVERING 3.5 MB OF THE DOWN-SYNDROME CONGENITAL HEART-DISEASE REGION BETWEEN D21S55 AND MX1 ON CHROMOSOME-21

Chromosome 21 is a model for the study of human chromosomal aneuploidy , and the construction of its physical and transcriptional maps is a n ecessary step in understanding the molecular basis of aneuploidy-depen dent phenotypes. To identify the gene(s) responsible for Down syndrome congenital heart disease (DS-CHD), we constructed a physical map of t he D21S55 to MX1 region. A bacterial artificial chromosome (BAG) libra ry was screened using several YACs spanning the interval, and a PI-der ived artificial chromosome (PAC) library was screened using radiolabel ed STS PCR products and whole BACs in gap-filling initiatives. FISH co nfirmed the location of all BAC and PAC clones to 21q22.2-q22.3. Overl aps were established using clone-to-clone Southerns and 24 new STSs, g enerated from the direct sequencing of BAC and PAC ends, along with 35 preexisting STSs. Approximately 3.5 Mb of the 4- to 5-Mb D21S55 to MX 1 interval is covered in 85 BACs and 24 PACs, representing fourfold co verage within the contigs. These BAC and PAC contigs are valuable reag ents for isolating the genes for DS-CHD. (C) 1997 Academic Press.