title: Distinct genetic signatures for variability in total and free serum thyroxine levels in four sets of recombinant inbred mice.
abstract: C3H/He and BALB/c mice have elevated serum thyroxine levels associated with low deiodinase type-1 activity whereas C57BL/6 (B6) mice have low thyroxine levels and elevated deiodinase type-1 activity. High-resolution genetic maps are available for four sets of recombinant inbred (RI) mice derived from B6 parents bred to C3H/He, BALB/c, DBA/2, or A strains. Total and free T4 (T-T4 and F-T4) levels in females from these RI sets (BXH, CXB, BXD, and AXBXA) were analyzed to test two hypotheses: first, serum T4 variability is linked to the deiodinase type-1 gene; second, because of their shared B6 parent, the RI sets will share linkages responsible for T-T4 or F-T4 variability. A number of chromosomes (Chr) and loci were linked to T-T4 (Chr 1, 4, 13, 11) or F-T4 (Chr 1, 6, 13, 18, 19). Linkage between T-T4 and Chr 4 was limited to CXB and BXH strains, but the locus was distinct from the deiodinase type-1 gene. Surprisingly, many linkages were unique providing "genetic signatures" for T-T4 or F-T4 in each set of RI mice. Indeed, the strongest linkage between T-T4 (or F-T4) and a Chr 2 locus (logarithm of the odds scores >4.4) was only observed in AXBXA strains. Some loci corresponded to genes/Chr associated in humans with variable TSH or T-T4 levels. Unlike inbred mice, human populations are extremely diverse. Consequently, our data suggest that the contributions of unique chromosomes/loci controlling T-T4 and F-T4 in distinct human subgroups are likely to be "buried" in genetic analyses of heterogeneous human populations.
authors.affiliation: Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and University of California, Los Angeles School of Medicine, Los Angeles, California 90048, USA. mclachlans@cshs.org
authors.forename: Sandra M
authors.initials: SM
authors.lastname: McLachlan
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Holly A
authors.initials: HA
authors.lastname: Aliesky
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Basil
authors.initials: B
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D016678:Genome; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D013974:Thyroxine / Q000097:blood* / Q000235:genetics*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013974:Thyroxine; D000097564:Iodothyronine Deiodinase Type II