Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  14
• Reference
  J:171768 Sinke AP, et al., Genetic analysis of mouse strains with variable serum sodium concentrations identifies the Nalcn sodium channel as a novel player in osmoregulation. Physiol Genomics. 2011 Mar 16;43(5):265-70
• ID
  MGI:7286101

Genes

Gene	Assay Type
Ssc3	visible phenotype
Ssc5	visible phenotype

Notes

• Experiment
  In central osmoregulation, a 1-2% rise in plasma osmolality is detected by specialized osmoreceptors located in the circumventricular organs of the hypothalamus. A disturbance in this tightly regulated balance will result in either hyponatremia or hypernatremia, which are both common electrolyte disorders in hospitalized patients.
  
  To identify novel genes involved in the (patho-)physiology of osmoregulation, the authors employed haplotype association mapping on an aging group of 27 inbred mouse strains (listed in Table 1; n = 20 per sex per strain). Serum sodium concentrations were determined in all strains at 6, 12, and 18 months of age, and high-resolution mapping was performed for males and females separately. Haplotype association mapping was performed as follows: trait data at strain mean levels were input as vectors, and genotype data (SNPs) across multiple inbred mouse strains were input as a matrix. A hidden Markov model (HMM) was applied, fitting five states at each SNP, for the primary purpose of missing genotype imputation and for the secondary purpose of haplotype identification. At each SNP, the strain distribution pattern was determined using the HMM smoothed haplotype states (HMMpath).
  
  With the imputed 63,222 SNP set with an average spacing of 40.53 Kb between each SNP, the authors obtained high-resolution mapping with small associated intervals.
  
  The authors identified a total of five suggestive loci associated with the serum sodium concentration (genome coordinates relative to NCBI37/mm9):
  
  Ssc1 (serum sodium concentration 1, 6 mos, males only) maps to Chr 5: 114.1 - 114.4 Mb with a peak LOD score of 3.64.
  
  Ssc2 (serum sodium concentration 2, 6 mos, males only) maps to Chr 7: 107.2 - 109.0 Mb with a peak LOD score of 3.76.
  
  Ssc3 (serum sodium concentration 3, 12 mos, females only) maps to Chr 14: 55.9 - 56.3 Mb with a peak LOD score of 4.42. Ssc3 contains only one known gene (Nalcn; MGI:2444306). Within this Ssc3 locus three different haplotypes could be distinguished, which associated with different average serum sodium levels.
  
  Ssc4 (serum sodium concentration 4, 18 mos, females only) maps to Chr 12: 114.6 - 114.8 Mb with a peak LOD score of 3.83.
  
  Ssc5 (serum sodium concentration 5, 18 mos, females) maps to Chr 14: 123.5 - 123.7 Mb with a peak LOD score of 4.53.
  
  The association of Nalcn with sodium levels was confirmed by analysis of heterozygous Nalcn knockout mice, which displayed hypernatremia compared with wild-type littermates.