title: A gene for hereditary pancreatitis maps to chromosome 7q35.
abstract: OBJECTIVE
  Hereditary pancreatitis (HP) is an autosomal-dominant disorder with incomplete penetrance characterized by recurrent bouts of severe epigastric pain with onset usually at 5-10 years of age. A genetic linkage study was designed to identify the HP gene.
  
  
  METHODS
  A 500-member pedigree was constructed from a U.S. kindred centered in eastern Kentucky and western Virginia. A genome-wide search strategy was employed using a 36-member subset of this family to determine the genetic locus for HP. Testing for linkage to microsatellite loci was performed at 20-cM intervals.
  
  
  RESULTS
  Linkage was established between the HP phenotype and chromosome 7q in this subset of the family. Modeled as an autosomal dominant disorder with 80% penetrance, a maximal multipoint logarithm of the odds score of 4.3 was obtained using a four-point analysis consisting of markers D7S684, D7S661, D7S505, and the HP locus. Two microsatellite markers, D7S661 and D7S505, that correspond to the 7q35 region of chromosome 7 spanning a 6-cM region did not evidence obligate recombinations with HP. The centromeric and telomeric limits are defined by recombinations at D7S684 and D7S483, respectively, which generates a 19-cM locus for HP. Utilizing family members from the extended pedigree, a break in the high-risk haplotype between D7S684 and D7S661 was observed, which suggests it may be possible to exclude an additional 8 cM from the HP locus. A maximal pairwise logarithm of the odds score of 4.73 at a recombination fraction of theta at D7S684 was obtained with the addition of these extended family members.
  
  
  CONCLUSIONS
  Linkage of HP to 7q35 represents a major advancement in our understanding of the genetic basis of this disorder.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA. Whitcomb+@pitt.edu
authors.forename: D C
authors.initials: DC
authors.lastname: Whitcomb
authors.forename: R A
authors.initials: RA
authors.lastname: Preston
authors.forename: C E
authors.initials: CE
authors.lastname: Aston
authors.forename: M J
authors.initials: MJ
authors.lastname: Sossenheimer
authors.forename: P S
authors.initials: PS
authors.lastname: Barua
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Wong-Chong
authors.forename: G J
authors.initials: GJ
authors.lastname: White
authors.forename: P G
authors.initials: PG
authors.lastname: Wood
authors.forename: L K
authors.initials: LK
authors.lastname: Gates
authors.forename: C
authors.initials: C
authors.lastname: Ulrich
authors.forename: S P
authors.initials: SP
authors.lastname: Martin
authors.forename: J C
authors.initials: JC
authors.lastname: Post
authors.forename: G D
authors.initials: GD
authors.lastname: Ehrlich
mesh_terms: D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D005796:Genes; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010195:Pancreatitis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype