An ~140-kb deletion associated with feline spinal muscular atrophy implies an essential<i>LIX1</i>function for motor neuron survival

Fyfe, John C.; Menotti‐Raymond, Marilyn; David, Victor A.; Brichta, Lars; Schäffer, Alejandro A.; Agarwala, Richa; Murphy, William J.; Wedemeyer, William J.; Gregory, Brittany L.; Buzzell, Bethany G.; Drummond, Meghan C.; Wirth, Brunhilde; O’Brien, Stephen J.

doi:10.1101/gr.5268806

Cited by 47 publications

(29 citation statements)

References 43 publications

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“…With knowledge of recombination distances across the cat genome, markers can be selected at even recombination intervals across the genome. We have utilized the genetic linkage map and these additional mapping resources in recent years to demonstrate that 1) a novel gene, LIX1 , is disrupted in feline spinal muscular atrophy in the cat [28], 2) the gene CEP290 is mutated in retinal degeneration in Abyssinian cats ( rdAc ) [29], which is a model of human retinal degeneration, 3) FGF5 is mutated in long-haired cats [30], 4) MLPH is mutated in dilute cats [31], (5) ASIP is mutated in black cats and MC1R is implicated in melanism in the jaguar and jagaroundi [32], (6) TYRP1 is mutated in brown and cinnamon cats [33]. Mutations in TYR have also been reported as causative of Siamese and Burmese phenotypes [34; 33].…”

Section: Discussionmentioning

confidence: 99%

An autosomal genetic linkage map of the domestic cat, Felis silvestris catus

et al. 2009

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We report on the completion of an autosomal genetic linkage (GL) map of the domestic cat (Felis silvestris catus). Unlike two previous linkage maps of the cat constructed with a hybrid pedigree between the domestic cat and the Asian leopard cat, this map was generated entirely with domestic cats, using a large multi-generational pedigree (n=256) maintained by the Nestlé Purina PetCare Company. Four hundred eighty-three simple tandem repeat (STR) loci have been assigned to linkage groups on the cat’s 18 autosomes. A single linkage group spans each autosome. The length of the cat map, estimated at 4370 cM, is long relative to most reported mammalian maps. A high degree of concordance in marker order was observed between the third-generation map and the 1.5 Mb-resolution radiation hybrid (RH) map of the cat. Using the cat 1.9X whole-genome sequence, we identified map coordinates for 85#x00025; of the loci in the cat assembly, with high concordance observed in marker order between the linkage map and the cat sequence assembly. The present version represents a marked improvement over previous cat linkage maps as it (i) nearly doubles the number of markers that were present in the second-generation linkage map in the cat, (ii) provides a linkage map generated in a domestic cat pedigree which will more accurately reflect recombination distances than previous maps generated in a hybrid pedigree, and (iii) provides single linkage groups spanning each autosome. Marker order was largely consistent between this and the previous maps, though the use of a hybrid pedigree in the earlier versions appears to have contributed to some suppression of recombination. The improved linkage map will provide an added resource for the mapping of phenotypic variation in the domestic cat and the use of this species as a model system for biological research.

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Section: Discussionmentioning

confidence: 99%

An autosomal genetic linkage map of the domestic cat, Felis silvestris catus

et al. 2009

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“…Lix1-l has been defined only by its sequence similarity to Lix1. The biological functions of these genes have not been described, although genetic mapping of a feline spinal muscular atrophy identified LIX1 as a candidate gene (Fyfe et al, 2006). …”

Section: Introductionmentioning

confidence: 99%

Drosophila lowfat, a novel modulator of Fat signaling

2009

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The Fat-Hippo-Warts signaling network regulates both transcription and planar cell polarity. Despite its crucial importance to the normal control of growth and planar polarity, we have only a limited understanding of the mechanisms that regulate Fat. We report here the identification of a conserved cytoplasmic protein, Lowfat (Lft), as a modulator of Fat signaling. Drosophila Lft, and its human homologs LIX1 and LIX1-like, bind to the cytoplasmic domains of the Fat ligand Dachsous, the receptor protein Fat,and its human homolog FAT4. Lft protein can localize to the sub-apical membrane in disc cells, and this membrane localization is influenced by Fat and Dachsous. Lft expression is normally upregulated along the dorsoventral boundary of the developing wing, and is responsible for elevated levels of Fat protein there. Levels of Fat and Dachsous protein are reduced in lftmutant cells, and can be increased by overexpression of Lft. lftmutant animals exhibit a wing phenotype similar to that of animals with weak alleles of fat, and lft interacts genetically with both fat and dachsous. These studies identify Lft as a novel component of the Fat signaling pathway, and the Lft-mediated elevation of Fat levels as a mechanism for modulating Fat signaling.

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“…These include mutations in functional candidate genes that control coat morphology [5; 6; 7], as well as those that are causative for monogenic diseases such as polycystic kidney disease [8], and hypertrophic cardiomyopathy [9]. The maps were also used in genome scans to identify disease genes not previously implicated in human studies at the time of the scan [10; 11], suggesting the value of multiple animal models in understanding the pathogenesis of human disease. The ability to narrow candidate regions and identify causative mutations in the feline model is currently limited by appropriate animal cohorts and by the quality of feline-human comparative gene maps.…”

Section: Introductionmentioning

confidence: 99%

A high-resolution cat radiation hybrid and integrated FISH mapping resource for phylogenomic studies across Felidae

et al. 2009

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We describe the construction of a high-resolution radiation hybrid (RH) map of the domestic cat genome, which includes 2,662 markers, translating to an estimated average intermarker distance of 939 kilobases (Kb). Targeted marker selection utilized the recent feline 1.9x genome assembly, concentrating on regions of low marker density on feline autosomes and the X chromosome, in addition to regions flanking interspecies chromosomal breakpoints. Average gap (breakpoint) size between cat-human ordered conserved segments is less than 900 Kb. The map was used for a fine-scale comparison of conserved syntenic blocks with the human and canine genomes. Corroborative fluorescence in situ hybridization (FISH) data were generated using 129 domestic cat BAC-clones as probes, providing independent confirmation of the long-range correctness of the map. Cross-species hybridization of BAC probes on divergent felids from the genera Profelis (serval) and Panthera (snow leopard) provides further evidence for karyotypic conservation within felids, and demonstrates the utility of such probes for future studies of chromosome evolution within the cat family and in related carnivores. The integrated map constitutes a comprehensive framework for identifying genes controlling feline phenotypes of interest, and to aid in assembly of a higher coverage feline genome sequence.

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An ~140-kb deletion associated with feline spinal muscular atrophy implies an essentialLIX1function for motor neuron survival

Cited by 47 publications

References 43 publications

An autosomal genetic linkage map of the domestic cat, Felis silvestris catus

An autosomal genetic linkage map of the domestic cat, Felis silvestris catus

Drosophila lowfat, a novel modulator of Fat signaling

A high-resolution cat radiation hybrid and integrated FISH mapping resource for phylogenomic studies across Felidae

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