Dahl (S × R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats

Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP) quantitative trait loci (QTLs) that co-localized with navigational performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5)), diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5)), and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5)) compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM) task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05). The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males

Congenic analysis of <i>Nav-5</i> QTL region on chromosome 17.

<p>On the left of the figure is shown the relevant region of the physical map of rat chromosome 17. Values in parenthesis next to the marker names denote physical locations in base pairs. The mapped <i>Nav-5</i> QTL region of approximately 9.64 Mbp is noted (to the right). Congenic strains are shown as solid bars (representing the Dahl R introgressed fragments) flanked by open bars (representing the putative regions of recombination).</p

Annotated genes in rat chromosome 2 176.6–179.9 Mbp region.

<p>Gene list and gene locations on rat chromosome 2 176.6–179.9 Mbp region as per NCBI Rat Genome Assembly v3.4.</p

Congenic analysis of <i>BP-f4/Nav-8</i> QTL region on chromosome 2.

<p>On the left of the figure is shown the relevant region of the physical map of rat chromosome 2. Values in parenthesis next to the marker names denote physical locations in base pairs. The mapped <i>BP-f4/Nav-8</i> QTL region of approximately 3.26 Mbp is noted (to the right). Congenic strains are shown as solid bars (representing the Dahl R introgressed fragments) flanked by open bars (representing the putative regions of recombination).</p

Overlapping blood pressure and spatial navigation QTLs detected in F2 (Dahl S×R) intercross rats.

<p>QTL, quantitative trait locus; BP, blood pressure; Nav, spatial navigation; Chr, chromosome.</p