Construction of a high-resolution linkage map for Xp22.1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene
- Institut de Chimie Biologique, Strasbourg (France); and others
The genes responsible for two X-linked diseases, the Coffin-Lowry syndrome (CLS) and juvenile retinoschisis (RS), have been previously mapped, through linkage studies, to an 8-cM region, in Xp22.1-p22.2, flanked distally by two tightly linked markers, DXS207 and DXS43, and proximally by DXS274. In the present study, five Genethon markers have been assigned to the (DXS207, DXS43) - DXS274 interval using somatic cell hybrids and a meiotic breakpoint panel and ordered together with three markers previously mapped to this region. A genetic map, which includes 13 loci and spans a distance of approximately 13 cM, was derived from linkage analysis using the CEPH families. The most likely locus order and map distances (in centimorgans) are Xpter - DXS16 - (3.4) - (DXS207, DXS43, DXS1053) - (2.0) - (DXS999, DXS257) - (1.7) - AFM291wf5 - (1.4) - DXS443 - (2.0) - (DXS1229, DXS3654) - (2.1) - (DXS1052, DXS274, DXS41) - Xcen. Analysis of multiple informative crossovers established AFM291wf5 and DXS1052 as new flanking markers for CLS, which significantly reduces the candidate region for this disease gene to a 4- to 5-cM interval. Three markers, DXS443, DXS1229, and DXS365, mapping within this interval showed complete cosegregation with the disease phenotype, giving a multipoint lod score of 14.2. The present map provides the framework for constructing a YAC contig for the CLS and RS region and should be useful for refining the localization of other disease genes mapping to this region. The panel of somatic cell hybrids characterized for the present study has also allowed us to refine the localization of five genes (CALB3, GRPR, PDHA1, GLRA2, and PHKA2) and two expressed sequence tags (DXS1118E and DXS1006E) previously assigned to the Xp22 region. 35 refs., 4 figs., 3 tabs.
- OSTI ID:
- 186033
- Journal Information:
- Genomics, Vol. 22, Issue 3; Other Information: PBD: Aug 1994
- Country of Publication:
- United States
- Language:
- English
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BASIC STUDIES
GENES
GENE MUTATIONS
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN X CHROMOSOME
CROSSING-OVER
MEIOSIS
RESOLUTION
PATIENTS
SENSE ORGANS DISEASES
CONGENITAL MALFORMATIONS
MENTAL DISORDERS
SOMATIC CELLS
HYBRIDIZATION
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STATISTICS
BIOLOGICAL MARKERS
YEASTS
CONTIGS
POLYMERASE CHAIN REACTION
NUCLEOTIDES
RFLPS