Analysis of symmetrical region near the centromeric end of 15q to identify its likeliest arrangement in RP11

The region between the most proximal segments P ordered as in Figure 5 is indicated by the four rows of segments at the top. The first row, continuing to the third row, represents the upper RP11 haplotigs in Figure 5 and the second row, continuing to the fourth row, represents the lower haplotigs. The RP11 haplotigs are shown below the segments with the non-RP11 clones shown further below. Nine slices of 5 to 30 kilobases (kb), shown by alternating red or blue lines, were investigated, with each box showing the number of single nucleotide mismatches between each pair of RP11 haplotigs and non-RP11 clones in the slice.<p><b>Copyright information:</b></p><p>Taken from "Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi, Angelman, and inv dup(15) syndromes"</p><p>http://genomebiology.com/2007/8/6/R114</p><p>Genome Biology 2007;8(6):R114-R114.</p><p>Published online 15 Jun 2007</p><p>PMCID:PMC2394762.</p><p></p

Is haplotype tagging the panacea to association mapping studies?

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Evaluation of the positional candidate gene CHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13?14

A previous study of 34 nuclear pedigrees segregating juvenile myoclonic epilepsy (JME) gave significant evidence of linkage with heterogeneity to marker loci on chromosome 15q13-14 close to the candidate gene CHRNA7 (Hum. Mol. Genet. 6 (1997) 1329). The aim of this work was to further evaluate the putative aetiological role of CHRNA7 in JME within the 34 families originally described, and to assess the contribution of this locus to a broader phenotype of idiopathic generalised epilepsy (IGE). Multipoint linkage analysis and intrafamilial association studies were performed with microsatellite markers that encompass both CHRNA7 and its partial duplication (CHRFAM7A). A maximum HLOD of 3.45 [alpha=0.58; (Zall=2.88, P=0.0008)] was observed 8 cM distal to D15S1360, a CHRNA7 intragenic marker. Significant exclusion lod scores were obtained across the region in 12 mixed phenotype JME/IGE families. Mutation screening of the CHRNA7 gene (and consequently exons 5-10 of CHRFAM7A) and its putative promoter sequence identified a total of 13 sequence variants across 23 of 34 JME-affected families. Two variants (c.1354G>A and c.1466C>T) are predicted to result in amino acid changes and one (IVS9+5G>A) is predicted to result in aberrant transcript splicing. However, none of the variants alone appeared either necessary or sufficient to cause JME in the families in which they occurred. In conclusion, linkage analyses continue to support the existence of a locus on chromosome 15q13-14 that confers susceptibility to JME but not to a broader IGE phenotype. Causal sequence variants in the positional candidate CHRNA7 have not been identified but the presence of multiple segmental duplications in this region raises the possibility of undetected disease-causing genomic rearrangements