Quantitative Trait Locus Analysis for Chronic Pancreatitis and Diabetes Mellitus in the WBN/Kob Rat

• Published in: Genomics (San Diego, Calif.) Vol. 74; no. 3; pp. 365 - 369
• Main Authors: Tsuji, Atsushi, Nishikawa, Tetsu, Mori, Masayuki, Suda, Koichi, Nishimori, Isao, Nishimura, Masahiko
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15-06-2001; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - genetics; CFTR gene; chromosome 7; Chromosome Mapping; Chronic Disease; Classical genetics, quantitative genetics, hybrids; Crosses, Genetic; Diabetes Mellitus - genetics; Diabetes Mellitus - pathology; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genome; Genotype; Insulin - blood; Male; Microsatellite Repeats; Pancreatitis - genetics; Pancreatitis - pathology; PRSS1 gene; Quantitative Trait, Heritable; Rats; Rats, Inbred BN; SPINK1 gene; Vertebrata; Endocrinopathy; Genetic mapping; Hyperinsulinemia; Animal model; Rat; Quantitative character; Diabetes mellitus; Rodentia; Pancreatitis; Chromosome; Vertebrata; Chronic; Mammalia; Digestive diseases; Pancreatic disease
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2001.6557

A causative gene mutation is still undefined in approximately half of patients with hereditary pancreatitis, and no genetic factor has been identified in most patients with sporadic chronic pancreatitis. To identify a pancreatitis-associated gene, we performed a quantitative trait locus (QTL) analysis for the traits of chronic pancreatitis and diabetes mellitus in WBN/Kob rats. We identified two highly significant QTLs for chronic pancreatitis and/or hyperinsulinemia on chromosomes 7 and X. These QTLs were located on completely different chromosomal regions from those of causative genes that have been reported for human chronic pancreatitis: PRSS1, CFTR, and SPINK1. For these QTLs, prevalences of the WBN/Kob allele significantly increased in the rats with chronic pancreatitis. These findings indicate that chronic pancreatitis in WBN/Kob rats is controlled by multiple genes, and a genetic analysis in WBN/Kob rats might be useful for gene targeting for human chronic pancreatitis.