Genetic Effects on Dispersion in Urinary Albumin and Creatinine in Three House Mouse (Mus musculus) Cohorts

Guy M. L. Perry
2019 G3: Genes, Genomes, Genetics  
Conventionally, quantitative genetics concerns the heredity of trait means, but there is growing evidence for the existence of architectures in which certain alleles cause random variance in phenotype, termed 'phenotypic dispersion' (PD) or 'variance QTL' (vQTL), including in physiological traits like disease signs. However, the structure of this phenomenon is still poorly known. PD for urinary albumin (PDUAlb) and creatinine (PDUCrea) was mapped using curated data from two nearly genetically
more » ... early genetically identical F2 mouse (Mus musculus) cohorts (383 male F2 C57BL/6J×A/J (97 SNP) and 207 male F2 C57BL/6J×A/J ApoE knockout mice (144 SNP)) and a related mapping cohort (340 male F2 DBA/2J×C57BL/6J (83 SNP, 8 microsatellites)). PDUAlb was associated with markers in regions of Chr 1 (5-64 megabases (MB); 141-158 MB), 3 (∼113 MB), 8 (37-68 MB), 14 (92-117 MB) and 17 (14-24 MB) with several positions and quantitative architectures in common between the two C57BL/6J×A/J cohorts, most of which had a negative dominant construction. One locus for PDUCrea was detected on Chr 19 (57 MB) in the C57BL/6J×A/J ApoE-/- cohort. The large number of negative dominant loci for albuminuria dispersion relative to conventional quantitative trait loci suggests that the development of albuminuria may be largely genetically dynamic and that randomization in this development is detrimental.
doi:10.1534/g3.118.200940 pmid:33575775 fatcat:qfzy5uwc2fg2jijdjo67hc5hde