Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis. 1991

E R Maher, and E Bentley, and J R Yates, and F Latif, and M Lerman, and B Zbar, and N A Affara, and M A Ferguson-Smith
Department of Pathology, University of Cambridge, United Kingdom.

Genetic linkage studies were performed in 22 families with von Hippel-Lindau (VHL) disease by using polymorphic DNA markers from distal chromosome 3p. Linkage was detected between VHL disease and the markers D3S18 (Zmax = 6.6 at theta = 0.0, confidence interval (CI) 0.00-0.06), RAF1 (Zmax = 5.9 at theta = 0.06, CI 0.01-0.16), and THRB (Zmax 3.4 at theta = 0.11). Multipoint linkage analysis localized the VHL disease gene within a small region (approximately 8 cM) of 3p25-p26 between RAF1 and (D3S191, D3S225) and close to the D3S18 locus. There was no evidence of locus heterogeneity, and families with and without pheochromocytoma showed linkage to D3S18. The identification of DNA markers flanking the VHL disease gene allows reliable presymptomatic and prenatal diagnosis to be offered to informative families.

UI MeSH Term Description Entries
D008040 Genetic Linkage The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME. Genetic Linkage Analysis,Linkage, Genetic,Analyses, Genetic Linkage,Analysis, Genetic Linkage,Genetic Linkage Analyses,Linkage Analyses, Genetic,Linkage Analysis, Genetic
D008126 Lod Score The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds." Lod Scores,Score, Lod,Scores, Lod
D010673 Pheochromocytoma A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of EPINEPHRINE and NOREPINEPHRINE, is HYPERTENSION, which may be persistent or intermittent. During severe attacks, there may be HEADACHE; SWEATING, palpitation, apprehension, TREMOR; PALLOR or FLUSHING of the face, NAUSEA and VOMITING, pain in the CHEST and ABDOMEN, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1298) Pheochromocytoma, Extra-Adrenal,Extra-Adrenal Pheochromocytoma,Extra-Adrenal Pheochromocytomas,Pheochromocytoma, Extra Adrenal,Pheochromocytomas,Pheochromocytomas, Extra-Adrenal
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D002893 Chromosomes, Human, Pair 3 A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification. Chromosome 3
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005190 Family A social group consisting of parents or parent substitutes and children. Family Life Cycles,Family Members,Family Life Cycle,Family Research,Filiation,Kinship Networks,Relatives,Families,Family Member,Kinship Network,Life Cycle, Family,Life Cycles, Family,Network, Kinship,Networks, Kinship,Research, Family
D005819 Genetic Markers A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. Chromosome Markers,DNA Markers,Markers, DNA,Markers, Genetic,Genetic Marker,Marker, Genetic,Chromosome Marker,DNA Marker,Marker, Chromosome,Marker, DNA,Markers, Chromosome
D006623 von Hippel-Lindau Disease An autosomal dominant disorder caused by mutations in a tumor suppressor gene. This syndrome is characterized by abnormal growth of small blood vessels leading to a host of neoplasms. They include HEMANGIOBLASTOMA in the RETINA; CEREBELLUM; and SPINAL CORD; PHEOCHROMOCYTOMA; pancreatic tumors; and renal cell carcinoma (see CARCINOMA, RENAL CELL). Common clinical signs include HYPERTENSION and neurological dysfunctions. Cerebelloretinal Angiomatosis, Familial,Lindau Disease,Angiomatosis Retinae,Familial Cerebello-Retinal Angiomatosis,Hippel-Lindau Disease,Lindau's Disease,VHL Syndrome,von Hippel-Lindau Syndrome,Angiomatoses, Familial Cerebello-Retinal,Angiomatoses, Familial Cerebelloretinal,Angiomatosis, Familial Cerebello-Retinal,Angiomatosis, Familial Cerebelloretinal,Cerebello-Retinal Angiomatoses, Familial,Cerebello-Retinal Angiomatosis, Familial,Cerebelloretinal Angiomatoses, Familial,Familial Cerebello Retinal Angiomatosis,Familial Cerebello-Retinal Angiomatoses,Familial Cerebelloretinal Angiomatoses,Familial Cerebelloretinal Angiomatosis,Hippel Lindau Disease,Lindau's Diseases,Lindaus Disease,VHL Syndromes,von Hippel Lindau Disease,von Hippel Lindau Syndrome

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