Exclusion of epidermal growth factor and high-resolution physical mapping across the Rieger syndrome locus. Am J Hum Genet 1996 Dec;59(6):1288-96
Date
12/01/1996Pubmed ID
8940274Pubmed Central ID
PMC1914874Scopus ID
2-s2.0-19244364500 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
We have evaluated the 4q25-4q26 region where the autosomal dominant disorder Rieger syndrome has been previously mapped by linkage. We first excluded epidermal growth factor as a candidate gene by carrying out SSCP analysis of each of its 24 exons using a panel of seven unrelated individuals with Rieger syndrome. No evidence for etiologic mutations was detected in these individuals, although four polymorphic variants were identified, including three that resulted in amino acid changes. We next made use of two apparently balanced translocations, one familial and one sporadic, to identify a narrow physical localization likely to contain the gene or to be involved in regulation of gene function. Somatic cell hybrids were established from individuals with these balanced translocations, and these hybrids were used as a physical mapping resource for, first, preliminary mapping of the translocation breakpoints using known sequence tagged sites from chromosome 4 and then, after creating YAC and cosmids contigs encompassing the region, for fine mapping of those breakpoints. A cosmid contig spanning these breakpoints was identified and localized the gene to within approximately 150 kb of D4S193 on chromosome 4. The interval between the two independent translocations is approximately 50 kb in length and provides a powerful resource for gene identification.
Author List
Semina EV, Datson NA, Leysens NJ, Zabel BU, Carey JC, Bell GI, Bitoun P, Lindgren C, Stevenson T, Frants RR, van Ommen G, Murray JCAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Chromosome MappingChromosomes, Human, Pair 4
Craniofacial Abnormalities
Epidermal Growth Factor
Genetic Markers
Glaucoma
Humans
Polymorphism, Single-Stranded Conformational
Sequence Analysis, DNA
Syndrome
Tooth Abnormalities
Translocation, Genetic
Umbilicus