Fig. 4

Haplotype analysis of families with CNVs in 19q13. Phasing analysis of genotypes to generate the most likely haplotype in pedigrees with CNVs on chromosome 19q13, was carried out with the GENEHUNTER software. Forty-seven markers representing all available markers in this region, spanning a region of 17.04 Mb, were included for the haplotype analysis. To simplify illustration of results, flanking markers were removed and only genotypes for 33 markers most proximal to the CNV are depicted, mapping a 6.05 Mb region. The linkage peak region is marked with a gray window and spans 1.5 Mb. The region with the two adjacent significant CNV-weighted linkage scores (91,215 bp in size) is illustrated with a gray dashed line. CNVs of duplication are denoted ‘dupl’, deletions are denoted ‘del’ and the normal state (wild type) are denoted ‘wt’. Haplotypes are displayed in colors (only for relevant chromosomes) to illustrate inheritance of gain/loss of genomic segments. The relative genomic region of each CNV is illustrated by separate colored segments. Of note, CNV calling was made based on a complete set of non-QC filtered sample of both monomorphic and polymorphic probes whereas analysis of the haplotypes was made using QC filtered polymorphic probes only. In order to retrieve recombinant mapping of high resolution, all available SNP-markers located within the linkage peak region were included. Representative gene-id’s are displayed. All genomic coordinates are according to NCBI36/hg18. a Results of the initial analysis of CNV-weighted linkage scores with 5 pedigrees consisting of 12 individuals with a shared CNV. In pedigree 29–0174 no DNA was available for individual 29–10665 who was therefore excluded from the initial CNV-weighted analysis. The CNV status for this individual was revealed in the subsequent phased haplotype analysis. Moreover, in pedigree 20–1049 the CNV-carriership in 20–10855 was detected using the subsequent phased haplotype analysis. b Results of the extended analysis to find undetected CNV’s. In our first attempt to identify undetected CNV’s in this region we manually checked the CNV calling and identified 3 individuals with deletions, 11–11113, 11–112163 and 29–10511, and individual 29–10514 with a deletion in the adjacent region. Finally, a phased haplotype analysis indicates that the CNV in 29–10511 is a de novo event and that no transmission of CNV’s occurs in the pedigrees 11–130 and 11–156. This analysis further indicates deletions in 29–10665 and 20–10855