Improved predictive test for MEN2, using flanking dinucleotide repeats and RFLPs

Gene(s) for the autosomal dominant endocrine cancer syndromes, multiple endocrine neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B (MEN2B), and familial medullary thyroid carcinoma (MTC1) all map to the pericentromeric region of chromosome 10. Predictive testing for the inheritance of...

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Bibliographic Details
Published in:American journal of human genetics 1992-12, Vol.51 (6), p.1430-1442
Main Authors: HOWE, J. R, LAIRMORE, T. C, MISHRA, S. K, DOU, S, VEILE, R, WELLS, S. A, DONIS-KELLER, H
Format: Article
Language:English
Subjects:
AVAILABILITY
Base Sequence
BASIC BIOLOGICAL SCIENCES
Biological and medical sciences
BIOLOGICAL MARKERS
BIOLOGY
BODY
CARCINOMAS
CHROMOSOMES
Chromosomes, Fungal
Chromosomes, Human, Pair 10
DISEASES
DNA, Single-Stranded
ENDOCRINE DISEASES
ENDOCRINE GLANDS
Endocrinopathies
Female
General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes
Genetic Linkage
GENETIC MAPPING
Genetic Markers
GENETICS
Genome, Human
Genomic Library
Genotype
GLANDS
HUMAN CHROMOSOMES
Humans
HYBRIDIZATION
In Situ Hybridization, Fluorescence
Karyotyping
Male
man
MAPPING
Medical sciences
Molecular Sequence Data
multiple endocrine neoplasia
Multiple Endocrine Neoplasia - diagnosis
Multiple Endocrine Neoplasia - genetics
NEOPLASMS
ORGANS 550400 > Genetics
Pedigree
Polymorphism, Restriction Fragment Length
predictions
Predictive Value of Tests
Repetitive Sequences, Nucleic Acid
restriction fragment length polymorphism
RFLPS
TESTING
THYROID
type 2A
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Description
Summary:Gene(s) for the autosomal dominant endocrine cancer syndromes, multiple endocrine neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B (MEN2B), and familial medullary thyroid carcinoma (MTC1) all map to the pericentromeric region of chromosome 10. Predictive testing for the inheritance of mutant alleles in individuals at risk for these disorders has been limited by the availability of highly informative and closely linked flanking markers. We describe the development of eight new markers, including two PCR-based dinucleotide repeat polymorphisms and six RFLPs that flank the disease loci. One of the dinucleotide repeat markers (sJRH-1) derives from the RBP3 locus on 10q11.2 and has a PIC of .88. The other dinucleotide repeat (sTCL-1) defines a new locus, D10S176, that maps by in situ hybridization to 10p11.2 and has a PIC of .68. We have constructed a new genetic linkage map of the pericentromeric region of chromosome 10, on the basis of 13 polymorphisms at six loci, which places the MEN2A locus between the dinucleotide repeat markers, with odds of 5,750:1 over the next most likely position. Using this set of markers, predictive genetic testing of 130 at-risk individuals from six families segregating MEN2A revealed that 95% were jointly informative with flanking markers, representing a significant improvement in genetic testing capabilities.
ISSN:0002-9297
1537-6605