Peaks of Linkage Are Localized by a BAC/PAC Contig of the 6p Reading Disability Locus

DCDC2 is associated with reading disability and modulates neuronal development in the brain

“…Reported linkage intervals range widely: 13.4 cm (16.9 Mb) spanning D6S422 (pter) through D6S291 (14), 5 cm (4.8 Mb) spanning D6S464 through D6S258 (13), and 1.8 cm (7.9 Mb) spanning D6S299 through D6S273 (12) (physical distances were previously described in ref. 11). Subsequently, we identified a peak of association with a short tandem repeat (STR) marker, JA04 [NCBI identification (ID) no.…”

A detailed physical map of the 6p reading disability locus, including new markers and confirmation of recombination suppression

“…(Ahn et al 2001) We extended coverage through the centromeric portion with PAC and BAC clones and sequence from the Sanger Centre available through public domain and FTP servers (www.sanger.ac.uk/HGP/Chr6). Additional map elements were identified from the published literature (Bray-Ward et al 1996;Dib et al 1996;Feder et al 1996;Lauer et al 1997;Malaspina et al 1996) and public domain servers at the Cooperative Human Linkage Center (CHLC: lpg.nci.nih.gov/CHLC), the Genome Database (GDB: gdbwww.gdb.org), the National Center for Biotechnology Information (NCBI: www.ncbi.nlm.nih.gov), the Sanger Centre (www.sanger.ac.uk/HGP/Chr6), the Stanford Human Genome Center (SHGC: www-shgc.Stanford.edu), UniSTS (www.ncbi.nlm.nih.gov/ genome/sts), and the Whitehead Institute Center for Genome Research (WICGR: www-genome.wi.mit.edu).…”

“…2) spanning 10 Mb of the 6p21.3-22 RD locus, based on redundant clone contigs we published previously (Ahn and Gruen 1999;Ahn et al 2001;Bray-Ward et al 1996) and the published genomic contig and sequences from the Sanger Centre. The minimal tiling pathway consists of 88 genomic clones: 78 PACs, six BACs, and four cosmids.…”

“…In order to increase the density of genetic markers, we searched for STR sequences within the end-sequences from 19 YACs, 70 BACs and eight PACs generated by TAIL PCR (Liu and Whittier 1995) and inverse PCR methods (Silver 1991), The Institute for Genomic Research (TIGR) BAC end sequence consortium (www.tigr.org/tdb/humgen/ bac_end_search/bac_end_anno.html), and available genomic sequence from Sanger (www.sanger.ac.uk/HGP/Chr6) as described in Ahn et al (2001). The analysis identified 12 potentially polymorphic STRs available for generating novel markers, if demonstrated to be sufficiently variable.…”

“…In 1994, Cardon et al (1994) published a peak of linkage at marker D6S105. Subsequent studies reported linkage regions of 10-16 cM (7.7 Mb) spanning D6S109 (pter) through D6S306 (Grigorenko et al 1997), 13.4 cM (16.9 Mb) spanning D6S422 through D6S291 (Fisher et al 1999), 5 cM (4.8 Mb) spanning D6S461 through D6S258 (Gayán et al 1999), and 1.8 cM (7.9 Mb) spanning D6S299 through D6S273 (Grigorenko et al 2000) (physical distances are as described in Ahn et al 2001). Combining these studies, linkage mapping has defined an RD locus that spans 17 Mb (14.9 cM) between markers D6S109 and D6S291.…”