An Ancestral Ashkenazi Haplotype at the HMPS/CRAC1 Locus on 15q13–q14 Is Associated with Hereditary Mixed Polyposis Syndrome
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 incorr...
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Published in | American journal of human genetics Vol. 72; no. 5; pp. 1261 - 1267 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chicago, IL
Elsevier Inc
01.05.2003
University of Chicago Press The American Society of Human Genetics |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 0002-9297 1537-6605 |
DOI: | 10.1086/375144 |