A gene for hereditary pancreatitis maps to chromosome 7q35.
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.
Whitcomb
D C
DC
Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA. Whitcomb+@pitt.edu
Preston
R A
RA
Aston
C E
CE
Sossenheimer
M J
MJ
Barua
P S
PS
Zhang
Y
Y
Wong-Chong
A
A
White
G J
GJ
Wood
P G
PG
Gates
L K
LK
Ulrich
C
C
Martin
S P
SP
Post
J C
JC
Ehrlich
G D
GD
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