Open AccessPositional cloning of disease genes on chromosome 16
Author(s) -
Norman A. Doggett,
M. Bruening,
David F. Callen,
Melissa Gardiner,
Terry J. Lerner
Publication year - 1996
Language(s) - English
Resource type - Reports
DOI - 10.2172/212498
Subject(s) - batten disease , positional cloning , genetics , biology , exon , gene , neuronal ceroid lipofuscinosis , candidate gene , cosmid , haplotype , disease gene identification , chromosome 16 , genetic linkage , gene mapping , chromosome , mutation , locus (genetics) , allele , exome sequencing
The project seeks to elucidate the molecular basis of an important genetic disease (Batten`s disease) by molecular cloning of the affected gene by utilizing an overlapping clone map of chromosome 16. Batten disease (also known as juvenile neuronal ceroid lipofuscinosis) is a recessively inherited neurodegenerative disorder of childhood characterized by progressive loss of vision, seizures, and psychomoter disturbances. The Batten disease gene was genetically mapped to the chromosome region 16p 12.1 in close linkage with the genetic markers D16S299 and D16S298. Exon amplification of a cosmid containing D16S298 yielded a candidate gene that was disrupted by a 1 kb genomic deletion in all patients containing the most common haplotype for the disease. Two separate deletions and a point mutation altering a splice site in three unrelated families have confirmed the gene as the Batten disease gene. The disease gene encodes a novel 438 amino acid membrane binding protein of unknown function