Genetic Analysis of Substrain Divergence in Non-Obese Diabetic (NOD) Mice

G3 : Genes - Genomes - Genetics
Petr SimecekE H Leiter

Abstract

The non-obese diabetic (NOD) mouse is a polygenic model for type 1 diabetes that is characterized by insulitis, a leukocytic infiltration of the pancreatic islets. During ~35 years since the original inbred strain was developed in Japan, NOD substrains have been established at different laboratories around the world. Although environmental differences among NOD colonies capable of impacting diabetes incidence have been recognized, differences arising from genetic divergence have not been analyzed previously. We use both mouse diversity array and whole-exome capture sequencing platforms to identify genetic differences distinguishing five NOD substrains. We describe 64 single-nucleotide polymorphisms, and two short indels that differ in coding regions of the five NOD substrains. A 100-kb deletion on Chromosome 3 distinguishes NOD/ShiLtJ and NOD/ShiLtDvs from three other substrains, whereas a 111-kb deletion in the Icam2 gene on Chromosome 11 is unique to the NOD/ShiLtDvs genome. The extent of genetic divergence for NOD substrains is compared with similar studies for C57BL6 and BALB/c substrains. As mutations are fixed to homozygosity by continued inbreeding, significant differences in substrain phenotypes are to be expected. Thes...Continue Reading

References

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Citations

Jul 3, 2015·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Andrew P Morgan, Catherine E Welsh
Nov 12, 2016·BMC Genomics·James DenvirJung Han Kim
Aug 26, 2017·G3 : Genes - Genomes - Genetics·Petr SimecekGary A Churchill
Nov 23, 2019·Human Gene Therapy Methods·Deirdre M O'ConnorAnthony Donsante
Sep 18, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeremy J RacineDavid V Serreze

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Datasets Mentioned

BETA
SRP045183

Methods Mentioned

BETA
genotyping
chip
MDA
PCR
exome
exome sequencing

Software Mentioned

UnifiedGenotyper
R package
Ensembl
IGV
UnifiedGenotyper of Genome Analysis Toolkit
bwa
MDA
Ensembl Variant Effect Predictor
MouseDivGeno
Ensembl Effect Predictor

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