Characterization of a recombination event excluding the Harvey-ras-1 (H-ras-1) locus in a Ramano-Ward Long QT syndrome family linked to Chromosome 11q15 and isolation of a polymorphic repeat telomeric to H-ras-1
- Univ. of Michigan, Ann Arbor (United States)
- National Institutes of Health, Bethesda, MD (United States)
- Massachusetts Institute of Technology, Boston, MA (United States); and others
The Romano-Ward Long QT syndrome (RWLQTS) has been linked to 11p15.5 in several large families but demonstrates genetic heterogeneity, since in other families the RWLQTS phenotype is not linked to 11p15. To date, no recombinants between the H-Ras-1 locus and RWLQTS in families linked to 11p15 have been published. In a large family, we demonstrate linkage of RWLQTS to marker D11S932 on chromosome 11p15.4 with a LOD score of 3.14 ({theta}=0;90% penetrance). An unaffected individual and her two unaffected offspring inherited the affected haplotype for the H-ras-1 region telomeric to D11S932. All three have QTc measurements of {le} 0.40 seconds and no history of syncope, making the diagnosis of RWLQTS extremely unlikely. This suggests that, although the gene for the RWlQTS is linked to 11p15 in this family, a recombination event may have occurred that separated the RWLQTS gene from the affected H-ras-1 region haplotype. To investigate a possible telomeric recombination event, cosmids telomeric to H-ras-1 were isolated. A highly polymorphic, complex CA/CT repeat marker (78% heterozygosity) was characterized and its location telomeric to H-ras-1 verified by interphase FISH. The same three unaffected individuals had the affected allele for this marker, ruling our recombination telomeric to H-ras-1 but proximal to the new marker. As the most telemeric marker on 11p to date, this marker will aid the physical and genetic mapping of the 11p telomere. The potential recombination event in this family apparently excludes H-ras-1 as a candidate gene and may aid the localization of the RWLQTS gene linked to 11p15.5. However, it remains a possibility that another genetic locus on 11p15, in addition to the one near the H-ras-1 gene, can cause the RWLQTS phenotype. This is the first report of recombination between H-ras-1 and RWLQTS in a family linked to 11p15.
- OSTI ID:
- 134719
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1457
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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