8/14/2023 0 Comments Lg four combin![]() ![]() The LG/J strain also can regenerate damaged articular cartilage and is protected from post-traumatic osteoarthritis. The LG/J strain regenerates ear pinna tissues after a 2mm hole-punch while the SM/J strain does not. In addition to these diverse metabolic and skeletal phenotypes, the LG/J strain shows the rare ability to regenerate tissues after injury. The two strains also differ for maternal genetic effects on offspring growth and offspring adult metabolic traits and their cross has been useful in mapping parent-of-origin genetic effects on metabolic traits. The SM/J strain responds more strongly than LG/J to a high-fat diet for these metabolic traits. They also differ for a variety of metabolic traits including obesity, diabetes, and serum cholesterol, triglycerides, and free fatty acids levels. The parental strains and their crosses differ in skeletal morphology, including the size and shape of the skull, mandible, tooth morphology, long-bone lengths, and a variety of other skeletal elements as well as bone biomechanical and structural properties. LG/J and SM/J differ in many complex traits in addition to size and growth. The strains have remained phenotypically stable over time, except that the SM/J strain is now about 6g heavier than it was in Chai’s studies. This result has been confirmed in many quantitative trait locus (QTL) mapping studies. Early genetic studies of these two strains found the differences in body size are caused by many genes of individually small effects. They are at the extremes of the adult body size distribution among the common laboratory inbred strains and have been profitably studied for genetic variation in adult body size and growth. Subsequent to selection, the LG/J and SM/J strains are fully inbred and have been maintained at the Jackson Laboratory since the 1950s by brother-sister mating. Attempts to fix the SM/J strain or its Recombinant Inbred Strain offspring for the SM/J allele at agouti have resulted in strain failure. The SM/J strain is kept heterozygous at the agouti locus by mating black animals ( a/a) with their white-bellied agouti ( A w /a) siblings. It is unclear whether any of these strains are related to current laboratory inbred strains. SM/J was created from a pool of mice derived from four crosses of seven inbred strains: dilute brown agouti ( dba), silver chocolate ( sv ba), black and tan ( a t), pink-eyed, short-eared dilute brown agouti ( ps e dba), albino ( c), cinnamon spotted ( bs), and agouti ( a). LG/J was created from a pool of albino mice obtained from a commercial breeder over a nine-month period and selected for increased body size for over 50 generations. The LG/J (large) and SM/J (small) strains of inbred mice were independently derived from selection experiments for large and small body size at 60 days, respectively. Additionally, given the LG/J and SM/J phylogenetic context among inbred strains, these data contribute important information to the genomic landscape of the laboratory mouse. We show how integrating genomic sequence with QTL reduces the QTL search space and helps researchers prioritize candidate genes and nucleotides for experimental follow-up. Variants in QTL associated with metabolic (231 QTL identified in an F 16 generation) and developmental (41 QTL identified in an F 34 generation) traits were interrogated and we highlight candidate quantitative trait genes (QTG) and nucleotides (QTN) in a QTL on chr13 associated with variation in basal glucose levels and in a QTL on chr6 associated with variation in tibia length. We find that QTL are both over-represented in non-IBD regions and highly enriched for variants predicted to have a functional impact. We intersected these functional predictions with quantitative trait loci (QTL) mapped in advanced intercrosses of these two strains. We also identified polymorphisms between LG/J and SM/J that fall in regulatory regions and highly informative transcription factor binding sites (TFBS). We characterized amino-acid changing mutations using three algorithms: LRT, PolyPhen-2 and SIFT. We find that 39% of the LG/J and SM/J genomes are identical-by-descent (IBD). We identified small nucleotide variants (SNVs) and structural variants (SVs) in the LG/J and SM/J strains relative to the reference genome and discovered novel variants in these two strains by comparing their sequences to other mouse genomes. Here we present the whole-genome sequences of two inbred strains, LG/J and SM/J, which are frequently used to study variation in complex traits as diverse as aging, bone-growth, adiposity, maternal behavior, and methamphetamine sensitivity. The laboratory mouse is the most commonly used model for studying variation in complex traits relevant to human disease. ![]()
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