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Single nucleotide polymorphism (SNP) analysis of mouse quantitative trait loci for identification of candidate genes
  1. Y Yan,
  2. M Wang,
  3. W J Lemon,
  4. M You
  1. Department of Surgery and Alvin J Siteman Cancer Center, Washington University in St Louis, St Louis, Missouri, USA
  1. Correspondence to:
 Professor Ming You
 Department of Surgery and Alvin J Siteman Cancer Center, Washington University in St Louis, School of Medicine, 660 S Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA; yoummsnotes.wustl.edu

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Mouse models are widely used for studying polygenic traits underlying various diseases to identify the low penetrance disease susceptibility genes. Classical genetic studies using cross breeding of mouse strains with differing susceptibilities to different diseases have identified chromosomal regions associated with predisposition to lung tumours, lung injury, disease resistance, and seizure.1,2 The process, called quantitative trait loci (QTL) mapping, involves the use of evenly spaced polymorphic DNA markers to create landmarks across each chromosome to find correlations between marker alleles and the phenotypic variation.3 Inbred mouse strains vary in their susceptibility to lung tumours, lung injury, disease resistance, and seizures, with two extreme strains being A/J (susceptible) and C57BL/6J (B6, resistant).1,2 As the mouse genome sequences for both the A/J and B6 strains of mice have been completed, identification of candidate genes responsible for disease related QTL, mapped using these two strains of mice as parental strains, becomes feasible by undertaking single nucleotide polymorphism (SNP) analysis.

One set of mouse QTL is associated with genetic predisposition to lung tumour. In humans, the wide variety of carcinogens and varying degrees of exposure make identifying the predisposing genes difficult, but in a mouse model, such confounding variables can be controlled. There is evidence that, although lung cancer incidence is largely associated with environmental factors such as smoking or occupational exposure, genetic components are involved in lung cancer development. Genetic linkage studies using various strains of inbred mice mapped pulmonary adenoma susceptibility (Pas), pulmonary adenoma resistance (Par), and susceptibility to lung cancer (Sluc) loci.1 Recently, we have mapped three major QTL, named mouse lung tumour (MLT) 1–3, in 25 strains of mice with known susceptibility to lung cancer development, using a whole genome LD analysis with 5638 genetic markers.4 MLT1 locates between D4Mit50 and D4Mit361, MLT2 …

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