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New heart rate quantitative trait loci (QTL) on SHR chromosome 8
Author(s) -
Silva Gustavo José Justo,
Costa Pereira Alexandre,
Krieger José Eduardo
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1406-c
Hypertensive patients often display autonomic nervous system derangements manifested by heart rate changes, which may underlie primary or secondary phenomenon. To test the former hypothesis, we conducted a linkage analyses for QTL mapping of heart rate loci in a F2 intercross population [SHR x Brown Norway (BN)]. Basal heart rate showed increased values in SHR compared to the normotensive Brown Norway strain (365±3 vs. 314±6 bpm p<0.05 for SHR and BN, respectively). The linkage analysis uncored one heart rate QTL on 6,78cM of chromosome 8 with a 18.67 LR. Within this chromosomal interval there are 241 genes, including 75 known genes. Interestingly, a gene cluster encoding for nicotinic acetylcholine receptors subtypes α3 (Chrna3), α5 (Chrna5) and β4 (Chrnb4) is included. Comparative genomics analysis revealed a similar genomic structure of these nicotinic receptors subtypes sequences among human, mouse, rat, chicken and zebrafish, mainly in the exon regions. Moreover, computational analysis revealed the presence of single nucleotide polymorphisms (SNPs) in 3′/5′ untranslated region, introns, and exons (synonymous or nonsynonymous SNPs) in both humans (Ch15q24) and rats (Ch8q22). Our results uncovered a new QTL for heart rate, which may influence this phenotype. A gene cluster encoding nicotinic acetylcholine receptor subtypes is under investigation as a potential candidate gene.