Figure 2. .

Linkage and haplotype mapping of Carpenter syndrome to chromosome 6p12.1. A, Genomewide HLOD scores from 50K microarray data for families 1 and 2 combined, with the assumption of a consanguineous loop (second-cousin parents) in family 1. HLOD scores are given along the Y-axis, relative to genomic position (cM) on the X-axis. Note the significant peak (HLOD 4.8) in the centromeric region of chromosome 6. B, Representation of 50K SNP haplotypes (vertical bars) for chromosomes of affected individuals in families 1 and 2 and an additional sporadic case (subject 3734), all of whom are homozygous for the 434T→A (L145X) mutation in RAB23. Distinct haplotypes are represented by different shaded bars. On the basis of homozygosity, the critical region on chromosome 6 is defined by heterozygosity for SNPs rs7766181 (family 1) and rs1689237 (subject 3734). Within this, a smaller region (white bars) is identical in all affected individuals for 30 consecutive SNPs, suggesting a common ancestral origin of the L145X mutation. C, Genotyping of 13 selected SNPs spanning this identical segment in 10 individuals homozygous for the L145X mutation and 2 individuals homozygous for E137X. At left, the position of these SNPs is shown in relation to RAB23 and 8 additional genes within the 6p12.1-q11 region. Note that all patients with the L145X mutation share a common haplotype for seven consecutive SNPs; this is interrupted proximally in two Dutch patients, probably because of a shared recombination. From top to bottom, the genotyped SNPs are rs1925179, rs2397214, rs9296842, rs1547625, rs6927258, rs6906792, rs3904827, rs6934928, rs1343391, rs1224703, rs1850417, rs2343013, and rs1689237. Bra=Brazil; Den=Denmark; Neth=The Netherlands.