%0 Journal Article %J Circ Cardiovasc Genet %D 2011 %T High-resolution identity by descent mapping uncovers the genetic basis for blood pressure differences between spontaneously hypertensive rat lines. %A Bell, Rebecca %A Herring, Stacy M %A Gokul, Nisha %A Monita, Monique %A Grove, Megan L %A Boerwinkle, Eric %A Doris, Peter A %K Animals %K Blood Pressure %K Chromosome Mapping %K Female %K Gene Expression %K Genetic Predisposition to Disease %K Genotype %K Haplotypes %K Lod Score %K Male %K Molecular Sequence Data %K Polymorphism, Single Nucleotide %K Rats %K Rats, Inbred SHR %X

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.

METHODS AND 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.

%B Circ Cardiovasc Genet %V 4 %P 223-31 %8 2011 Jun %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/21406686?dopt=Abstract %R 10.1161/CIRCGENETICS.110.958934