THE HUMAN GENE FOR NEUROTROPHIC TYROSINE KINASE RECEPTOR-TYPE-2 (NTRK2) IS LOCATED ON CHROMOSOME-9 BUT IS NOT THE FAMILIAL DYSAUTONOMIA GENE

The neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene is a mem ber of the trk family of tyrosine protein kinases, which encode recept ors for the nerve growth factor-related proteins known as neurotrophin s. The neurotrophins and their receptors have long been considered can didate genes for familial dysautonomia (FD), a hereditary sensory neur opathy resulting from the congenital loss of both sensory and autonomi c neurons. The DYS gene has recently been mapped to human chromosome 9 q31-q33, and therefore we set out to determine the chromosomal localiz ation of the candidate gene NTRK2. A mouse trkB probe was hybridized t o both somatic cell hybrids containing human chromosome 9 and a human chromosome 9 how-sorted cosmid library, The human homologue of trkB, N TRK2 was assigned to chromosome 9. To localize the NTRK2 gene further, a dinucleotide repeat polymorphism was identified within a cosmid tha t contains NTRK;2 exon sequences. This marker was genotyped in the CEP H reference pedigrees and places the NTRK2 gene near D9S1 on the proxi mal long arm of human chromosome 9. The NTRK2 gene is located approxim ately 22 cm proximal to DYS and shows several recombinants in disease families. Therefore, the NTRK2 gene can now be excluded as a candidate gene for familial dysautonomia. (C) 1995 Academic Press, Inc.