Fine resolution genetic mapping of galamin-GMAP (GALN) excludes a candidate gene for multiple endocrine neoplasia type 1 (MEN1)
- Univ. of Cleveland, OH (United States); and others
Galamin is a 30 amino acid peptide in the human that has been suggested to potentiate the release of growth hormone; inhibit insulin secretion; play a role in gonadotropin modulation, in neuronal regeneration, and in the control of satiety; may mediate estrogen`s mitogenic role in development of prolactinomas; and may be associated with the development of pituitary hyperplasia in hGHRH transgenic mice. The preprogalanin gene, GALN, is predominantly expressed in the pituitary, hypothalamus, duodenum and pancreas. A second peptide, GMAP, is produced by proteolysis of preprogalanin, but is of unknown function. We previously isolated a 200 kb YAC containing the human galanin gene and localized it to chromosome 11q13 by fluorescence in situ hybridization (FISH). The multiple endocrine neoplasia type 1 (MEN1) gene has also been assigned to 11q13. Tumors in MEN1 develop in the anterior pituitary, parathroid glands, neuroendocrine pancreas and the duodenum, which is similar to the expression specificity of GALN. Based on the similar gene localization and expression, we tested GALN as a candidate gene for MEN1. Studies of chromosome 11q13 have defined a genetic map, cen-D11S480-PYGM-MEN1-D11S146-INT2-tel. Whereas PCR analysis of a panel of radiation-reduced somatic cell hybrids from 11q13 mapped GALN distal to PYGM, and within the 1NT2 segregation group, the use of two-color FISH suggested a localization of GALN proximal to 1NT2. Subsequently, TaqI and SinI RFLPs in the GALN gene were identified and genotyped in a 228 member Venezuelan reference pedigree. Multipoint analysis suggested the order; cen-D11S480-[FAEES-III, GALN]-INT2-D11S527, with this order having 100:1 odds vs. placement of GALN distal to INT2. Since other studies place FAEES-III distal of MEN1, our studies exclude the GALN gene from having a role in MEN1.
- OSTI ID:
- 134022
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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