The Tabby cat locus maps to feline chromosome B1

The Tabby markings of the domestic cat are unique coat patterns for which no causative candidate gene has been inferred from other mammals. In this study, a genome scan was performed on a large pedigree of cats that segregated for Tabby coat markings, specifically for the Abyssinian (Ta-) and blotched (tbtb) phenotypes. There was linkage between the Tabby locus and eight markers on cat chromosome B1. The most significant linkage was between marker FCA700 and Tabby (Z = 7.56, theta = 0.03). Two additional markers in the region supported linkage, although not with significant LOD scores. Pairwise analysis of the markers supported the published genetic map of the cat, although additional meioses are required to refine the region. The linked markers cover a 17-cM region and flank an evolutionary breakpoint, suggesting that the Tabby gene has a homologue on either human chromosome 4 or 8. Alternatively, Tabby could be a unique locus in cats.     

Population Sizes and Distribution of Primates in the Lower Tana River Forests,Kenya

We studied the population size and distribution of diurnal primates in the lower Tana River forests, Kenya. They are the only remaining habitats for 2 threatened primates: the Tana River red colobus (Procolobus rufomitratus) and the Tana River crested mangabey (Cercocebus galeritus galeritus). We conducted censuses in 73 forest patches from January through March 2001. We estimate population size of the red colobus to be 788 individuals in 82 groups and that of the crested mangabeys to be 2,070 individuals in 59 groups. The data suggest that over a 7-year period (1994-2001), there was an 18% increase in the crested mangabey population and a 5% decline in red colobus numbers. Further, the red colobus range has expanded both north and south, whereas that of crested mangabeys has only expanded south. Fifty-six percent of crested mangabeys and 46% of red colobus groups were inside the Tana River Primate National Reserve (TRPNR). Other primates encountered included 170 groups of Sykes' monkeys (Cercopithecus mitis), 70 groups of yellow baboons (Papio cynocephalus) and 4 groups of grivets [Chlorocebus (Cercopithecus) aethiops]. Mean group densities of the 2 endangered primates and of baboons were higher inside than outside the TRPNR, reinforcing the importance of TRPNR for their conservation. An intervention program is required to stem further decline in the red colobus population and to protect small isolated groups in forest patches outside TRPNR.     

Diet‐induced early‐stage atherosclerosis in baboons: Lipoproteins,atherogenesis, and arterial compliance

Background

The purpose of this study was to determine whether dietary manipulation can reliably induce early‐stage atherosclerosis and clinically relevant changes in vascular function in an established, well‐characterized non‐human primate model.

Methods

We fed 112 baboons a high‐cholesterol, high‐fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy.

Results

We observed evidence of atherosclerosis in all but one baboon fed the two‐year challenge diet. CVD risk biomarkers, the prevalence, size, and complexity of arterial lesions, plus consequent arterial stiffness, were increased in comparison with dietary control animals.

Conclusions

Feeding baboons a high‐cholesterol, high‐fat diet for two years reliably induces atherosclerosis, with risk factor profiles, arterial lesions, and changes in vascular function also seen in humans.     

Primate census and habitat evaluation in the Tana delta region, Kenya

Nineteen indigenous forest patches in the Tana River delta region, Kenya were surveyed between October and November 2000 for primates and habitat disturbance. Special emphasis was placed on the endangered Tana River red colobus (Procolobus rufomitratus Peters) and crested mangabeys (Cercocebus galeritus galeritus Peters), both of which are endemic to the region. Habitat disturbances evident in the forests included cutting of trees, harvesting of thatching material, firewood collection, dyke construction, cultivation, palm wine tapping and charcoal burning. A total of 85 groups of five primate species were counted. These comprised eighteen, ten, 22, 31 and four groups of red colobus, crested mangabey, baboons (Papio cynocephalus L.), sykes monkeys (Cercopithecus mitis Wolf) and vervet monkeys (Cercopithecus aethiops L.), respectively. A wider distribution of red colobus and crested mangabeys than was documented previously was noted, implying that they are probably more abundant than hitherto reported. It is hypothesized that extensive studies on some fauna considered endangered world‐wide would probably redefine their conservation status. Future studies in the lower Tana River region should cover the previously unsurveyed forests and focus on ways of curbing forest destruction.     

Identification of candidate genes encoding an LDL-C QTL in baboons

Cardiovascular disease (CVD) is the leading cause of death in developed countries, and dyslipidemia is a major risk factor for CVD. We previously identified a cluster of quantitative trait loci (QTL) on baboon chromosome 11 for multiple, related quantitative traits for serum LDL-cholesterol (LDL-C). Here we report differentially regulated hepatic genes encoding an LDL-C QTL that influences LDL-C levels in baboons. We performed hepatic whole-genome expression profiling for LDL-C-discordant baboons fed a high-cholesterol, high-fat (HCHF) diet for seven weeks. We detected expression of 117 genes within the QTL 2-LOD support interval. Three genes were differentially expressed in low LDL-C responders and 8 in high LDL-C responders in response to a HCHF diet. Seven genes (ACVR1B, CALCOCO1, DGKA, ERBB3, KRT73, MYL6B, TENC1) showed discordant expression between low and high LDL-C responders. To prioritize candidate genes, we integrated miRNA and mRNA expression profiles using network tools and found that four candidates (ACVR1B, DGKA, ERBB3, TENC1) were miRNA targets and that the miRNAs were inversely expressed to the target genes. Candidate gene expression was validated using QRT-PCR and Western blotting. This study reveals candidate genes that influence variation in LDL-C in baboons and potential genetic mechanisms for further investigation.     

Differential microRNA response to a high-cholesterol, high-fat diet in livers of low and high LDL-C baboons

ABSTRACT: BACKGROUND: Dysregulation of microRNA (miRNA) expression has been implicated in molecular geneticevents leading to the progression and development of atherosclerosis. We hypothesized thatmiRNA expression profiles differ between baboons with low and high serum low-densitylipoprotein cholesterol (LDL-C) concentrations in response to diet, and that a subset of thesemiRNAs regulate genes relevant to dyslipidemia and risk of atherosclerosis. RESULTS: Using Next Generation Illumina sequencing methods, we sequenced hepatic small RNAlibraries from baboons differing in their LDL-C response to a high-cholesterol, high-fat(HCHF) challenge diet (low LDL-C, n = 3; high LDL-C, n = 3), resulting in 517 baboonmiRNAs: 490 were identical to human miRNAs and 27 were novel. We compared miRNAexpression profiles from liver biopsies collected before and after the challenge diet andobserved that HCHF diet elicited expression of more miRNAs compared to baseline (chow)diet for both low and high LDL-C baboons. Eighteen miRNAs exhibited differentialexpression in response to HCHF diet in high LDL-C baboons compared to 10 miRNAs in low LDL-C baboons. We used TargetScan/Base tools to predict putative miRNA targets;miRNAs expressed in high LDL-C baboons had significantly more gene targets thanmiRNAs expressed in low LDL-C responders. Further, we identified miRNA isomers andother non-coding RNAs that were differentially expressed in response to the challenge diet inboth high LDL-C and low LDL-C baboons. CONCLUSIONS: We sequenced and annotated baboon liver miRNAs from low LDL-C and high LDL-Cresponders using high coverage Next Gen sequencing methods, determined expressionchanges in response to a HCHF diet challenge, and predicted target genes regulated by thedifferentially expressed miRNAs. The identified miRNAs will enrich the database for noncodingsmall RNAs including the extent of variation in these sequences. Further, weidentified other small non-coding RNAs differentially expressed in response to diet. Ourdiscovery of differentially expressed baboon miRNAs in response to a HCHF diet challengethat differ by LDL-C phenotype is a fundamental step in understating the role of non-codingRNAs in dyslipidemia.     

A high-resolution radiation hybrid map of rhesus macaque chromosome 5 identifies rearrangements in the genome assembly

A 10,000-rad radiation hybrid (RH) cell panel of the rhesus macaque was generated to construct a comprehensive RH map of chromosome 5. The map represents 218 markers typed in 185 RH clones. The 4846-cR map has an average marker spacing of 798 kb. Alignments of the RH map to macaque and human genome sequences confirm a large inversion and reveal a previously unreported telomeric inversion. The macaque genome sequence indicates small translocations from the ancestral homolog of macaque chromosome 5 to macaque chromosomes 1 and 6. The RH map suggests that these are probably assembly artifacts. Unlike the genome sequence, the RH mapping data indicate the conservation of synteny between macaque chromosome 5 and human chromosome 4. This study shows that the 10,000-rad panel is appropriate for the generation of a high-resolution whole-genome RH map suitable for the verification of the rhesus genome assembly.     

Identification of baboon microRNAs expressed in liver and lymphocytes

Background  

MicroRNAs (miRNAs) are small noncoding RNAs (~22 nucleotides) that regulate gene expression by cleaving mRNAs or inhibiting translation. The baboon is a well-characterized cardiovascular disease model; however, no baboon miRNAs have been identified. Evidence indicates that the baboon and human genomes are highly conserved; based on this conservation, we hypothesized that comparative genomic methods could be used to identify baboon miRNAs.