Sequence variability and protein domain architectures for bovine Toll-like receptors 1, 5, and 10.

The mammalian Toll-like receptors (TLRs) play an important role in the recognition of invading pathogens and the modulation of innate immune responses. The primary objective of this study was to characterize single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (indels) within bovine TLRs 1, 5, and 10, thereby facilitating future TLR signaling and association studies relevant to bovine innate immunity. Comparative sequence analysis for 10 bovine breeds derived from Bos taurus and Bos indicus revealed 98 polymorphisms (92 SNPs and 6 indels), with at least 14 nonsynonymous SNPs located within predicted TLR domains considered to be of functional significance. Of the 98 polymorphisms detected, 94 are reported here for the first time. Notably, 2 nonsynonymous SNPs were determined to modulate the prediction of a novel leucine-rich repeat (LRR) domain within B. indicusTLR5. Prediction and comparison of TLR protein domain architectures for multiple species revealed seven conserved regions of LRR patterning associated with the three genes investigated.

Detection of polymorphisms in bovine toll-like receptors 3, 7, 8, and 9.

The toll-like receptors (TLRs) detect molecular signatures of invaders known as pathogen-associated molecular patterns (PAMPs). Ten members of the TLR family have been identified in cattle to date and 4 of these recognize PAMPs specific to viruses (TLRs 3, 7, 8, 9). The objective of this work was to detect polymorphisms in the genomic sequences of bovine TLRs 3, 7, 8, and 9. To achieve this objective, a panel of nine breeds representing Bos taurus and Bos indicus was assembled for sequencing and comparison with the Bovine Genome Project sequence. Comparative sequence analysis revealed a total of 139 polymorphisms, which include single-nucleotide polymorphisms and insertion-deletion polymorphisms. Of the 139 polymorphisms, 88% (N=123) are novel. In addition, the protein domain architecture of these four TLRs was examined between human, mouse, cow, and dog, which revealed several regions of conservation in the TLR variable leucine-rich-repeat patterning.

Assignment of canine MSS1 microsatellite markers to chromosomes by linkage data.

Recent advances in mapping the canine genome have led to an increase in the number of linkage studies aimed at dissecting the genetic causes of many hereditary diseases that affect the domestic dog. The first step in developing molecular tools for a whole genome scan was the characterization of a set of microsatellite markers, termed minimal screening set 1 (MSS1), that provided an estimated coverage of 10 cM. A limiting factor in use of the MSS1 is not all of the 172 MSS1 markers have been localized to specific chromosomes. Seventy-five of the markers were positioned on a total of 15 chromosomes with the original publication of the MSS1. The localization based on linkage data of 14 additional MSS1 markers to chromosomes using CRIMAP v. 2.4 to build a linkage map of 113 MSS1 markers that were polymorphic in a kindred of Dalmatians is reported here.

Heritability and segregation analysis of deafness in U.S. Dalmatians.

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Digging up the canine genome--a tale to wag about.

There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics and genomics is of importance to comparative genomics, evolutionary biology and study of human hereditary diseases. The most recent version of the map of the canine genome is comprised of 3,270 markers mapped to 3,021 unique positions with an average intermarker distance of approximately 1 Mb. The markers include approximately 1,600 microsatellite markers, about 1,000 gene-based markers, and almost 700 bacterial artificial chromosome-end markers. Importantly, integration of radiation hybrid and linkage maps has greatly enhanced the utility of the map. Additionally, mapping the genome has led directly to characterization of microsatellite markers ideal for whole genome linkage scans. Thus, workers are now able to exploit the canine genome for a wide variety of genetic studies. Finally, the decision to sequence the canine genome highlights the dog's evolutionary and physiologic position between the mouse and human and its importance as a model for study of mammalian genetics and human hereditary diseases.

Localization of a recessive juvenile cataract mutation to proximal chromosome 7 in mice.

OBJECTIVE: To localize the chromosomal position of a novel cataract mutation (juvenile recessive cataract; jrc) in mice. METHODS: A mapping population was developed by crossing cataract males (albino MH) to wild-type females (black C57BL/6J). F1 females were backcrossed to albino MH males with cataracts. RESULTS: The results were consistent with a model of a single autosomal recessive gene [153 cataract, 169 wild-type; chi2 = 0.8, 1 degree of freedom (d.f.), p > 0.35]. Linkage with the albino (tyrosinase; Tyr) locus was evident (chi2 = 61.5, 1 d.f., p < 0.0001), implicating chromosome 7 as the location of jrc. Recombination percentages (+/- SE) between jrc and D7Mit340 (1.2 cM location), D7Mit227 (16.0 cM) and D7Mit270 (18.0 cM) were 17.1 +/- 2.1, 3.7 +/- 1.1 and 6.2 +/- 1.3%, respectively. Multi-point mapping determined that the most likely order of these loci is D7Mit340 - jrc - D7Mit227 - D7Mit270 - Tyr. Although animals with the mutant phenotype appeared to have little or no sense of sight, their growth was not different (p >0.20) from that of normal mice. CONCLUSION: The jrc mutation model may be useful in the study of the genetics of cataracts in other animal species, including humans.