title: High-resolution identity by descent mapping uncovers the genetic basis for blood pressure differences between spontaneously hypertensive rat lines.
abstract: BACKGROUND
  The recent development of a large panel of genome-wide single nucleotide polymorphisms (SNPs) provides the opportunity to examine genetic relationships between distinct SHR lines that share hypertension but differ in their susceptibility to hypertensive end-organ disease.
  
  
  RESULTS
  We compared genotypes at nearly 10,000 SNPs obtained for the hypertension end-organ injury-susceptible spontaneously hypertensive rat (SHR)-A3 (SHRSP, SHR-stroke prone) line and the injury-resistant SHR-B2 line. This revealed that that the 2 lines were genetically identical by descent (IBD) across 86.6% of the genome. Areas of the genome that were not IBD were distributed across 19 of the 20 autosomes and the X chromosome. A block structure of non-IBD comprising a total of 121 haplotype blocks was formed by clustering of SNPs inherited from different ancestors. To test the null hypothesis that distinct SHR lines share a common set of hypertension susceptibility alleles, we compared blood pressure in adult SHR animals from both lines and their F1 and F2 progeny using telemetry. In 16- to 18-week-old animals fed a normal diet, systolic blood pressure (SBP, mm Hg) in SHR-A3 was 205.7 ± 3.86 (mean ± SEM, n = 26), whereas in similar SHR-B2 animals, SBP was 186.7 ± 2.53 (n = 20). In F1 and F2 animals, SBP was 188.2 ± 4.23 (n = 19) and 185.6 ± 1.1 (n = 211), respectively (P<10(-6), ANOVA). To identify non-IBD haplotype blocks contributing to blood pressure differences between these SHR lines, we developed a high-throughput SNP genotyping system to genotype SNPs marking non-IBD blocks. We mapped a single non-IBD block on chromosome 17 extending over <10 Mb, at which SHR-A3 alleles significantly elevate blood pressure compared with SHR-B2.
  
  
  CONCLUSIONS
  Thus hypertension in SHR-A3 and -B2 appears to arise from an overlapping set of susceptibility alleles, with SHR-A3 possessing an additional hypertension locus that contributes to further increase blood pressure.
authors.affiliation: Institute of Molecular Medicine, University of Texas HSC at Houston, Houston, TX 77030, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bell
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Herring
authors.forename: Nisha
authors.initials: N
authors.lastname: Gokul
authors.forename: Monique
authors.initials: M
authors.lastname: Monita
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Peter A
authors.initials: PA
authors.lastname: Doris
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*