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

ABSTRACT: 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 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.

SUBMITTER: Perry GML

PROVIDER: S-EPMC6404620 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Perry Guy M L GML

G3 (Bethesda, Md.) 20190307 3

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 mapp ...[more]

PMID: 30606755

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Project description:BACKGROUND: Insights into the micro-evolutionary patterns of morphological traits require an assessment of the natural variation of the trait within and between populations and closely related species. The mouse mandible is a particularly suitable morphological trait for such an analysis, since it has long been used as a model to study the quantitative genetics of shape. In addition, many distinct populations, sub-species and closely related species are known for the house mouse. However, morphological comparisons among wild caught animals require an assessment in how far environmental and technical factors could interfere with the shape change measurements. RESULTS: Using geometric morphometrics, we have surveyed mandible shapes in 15 natural populations of the genus Mus, with a focus on the subspecies Mus musculus domesticus. In parallel we have carefully assessed possibly confounding technical and biological factors. We find that there are distinct differences on average between populations, subspecies and species, but these differences are smaller than differences between individuals within populations. Populations from summer-dry regions, although more ancestral, are less distinct from each other than are populations from the more recently colonized northern areas. Populations with especially distinct shapes occur in an area of sympatry of M. m. domesticus and M. spretus and on recently colonized sub-antarctic islands. We have also studied a number of inbred strains to assess in how far their mandible shapes resemble those from the wild. We find that they fall indeed into the shape space of natural variation between individuals in populations. CONCLUSIONS: Although mandible shapes in natural populations can be influenced by environmental variables, these influences are insufficient to explain the average extent of shape differences between populations, such that evolutionary processes must be invoked to explain this level of diversity. We discuss that adaptive evolution may contribute to shape changes between populations, in particular in newly colonized areas. A comparison between inbred strains and wild mice suggests that the laboratory environment has no major systematic effect on the mandible shape and that such strains can be used as representatives of the natural shape differences between individuals.

Dataset Information

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

Publications

Genetic Effects on Dispersion in Urinary Albumin and Creatinine in Three House Mouse (<i>Mus musculus</i>) Cohorts.

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