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. 2003 May;72(5):1261-7.
doi: 10.1086/375144. Epub 2003 Apr 14.

An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome

E E M Jaeger  1 , K L Woodford-Richens, M Lockett, A J Rowan, E J Sawyer, K Heinimann, P Rozen, V A Murday, S C Whitelaw, A Ginsberg, W S Atkin, H T Lynch, M C Southey, H Debinski, C Eng, W F Bodmer, I C Talbot, S V Hodgson, H J W Thomas, I P M Tomlinson
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An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome

E E M Jaeger et al. Am J Hum Genet. 2003 May.

Abstract

The putative locus for hereditary mixed polyposis syndrome (HMPS) in a large family of Ashkenazi descent (SM96) was previously reported to map to chromosome sub-bands 6q16-q21. However, new clinical data, together with molecular data from additional family members, have shown 6q linkage to be incorrect. A high-density genomewide screen for the HMPS gene was therefore performed on SM96, using stringent criteria for assignment of affection status to minimize phenocopy rates. Significant evidence of linkage was found only on a region on chromosome 15q13-q14. Since this region encompassed CRAC1, a locus involved in inherited susceptibility to colorectal adenomas and carcinomas in another Ashkenazi family (SM1311), we determined whether HMPS and CRAC1 might be the same. We found that affected individuals from both families shared a haplotype between D15S1031 and D15S118; the haplotype was rare in the general Ashkenazi population. A third informative family, SM2952, showed linkage of disease to HMPS/CRAC1 and shared the putative ancestral haplotype, as did a further two families, SMU and RF. Although there are probably multiple causes of the multiple colorectal adenoma and cancer phenotype in Ashkenazim, an important one is the HMPS/CRAC1 locus on 15q13-q14.

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Figures

Figure 1
Figure 1
Pedigree of selected part of family SM96, showing haplotypes for the following chromosome 6 markers: D6S1716, D6S468, D6S283, D6S434, D6S1580, D6S301, D6S1592, and D6S447. Black bars denote the haplotype that was previously thought to segregate with disease. Known affected individuals are indicated by a blackened symbol. Inferred haplotypes are bracketed.
Figure 2
Figure 2
Pedigree of selected members of family SM96, showing haplotypes for the following chromosome 15 markers: D15S1031, D15S1010, D15S144, D15S995, D15S1007, D15S1040, ACTC, D15S971, and D15S118. Symbols are the same as in figure 1.
Figure 3
Figure 3
Pedigree of family SM2592, showing haplotypes for the same chromosome 15 markers as are shown in figure 2. Symbols are the same as in figure 1.
Figure 4
Figure 4
A sliding map of three markers was used to calculate multipoint linkage analysis between markers D15S1031 and D15S118. Combined genotyping data from families SM96, SM1311, and SM2592 were used.
See this image and copyright information in PMC

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References

Electronic-Database Information

    1. Genetic Location Database, http://cedar.genetics.soton.ac.uk/public_html/ldb.html (for marker selection)
    1. Genome Database, http://gdbwww.gdb.org/ (for marker allele frequencies)
    1. Online Mendelian Inheritance in Man (OMIM),http://www.ncbi.nlm.nih.gov/Omim/ (for HMPS) - PubMed

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