Publications by authors named "Frank W Nicholas"

40 Publications

Philosophy: Religion's openness towards science.

Authors:
Frank W Nicholas

Nature 2017 06;546(7659):474

University of Sydney, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/546474bDOI Listing
June 2017

Hybrid vigour in dogs?

Vet J 2016 Aug 30;214:77-83. Epub 2016 May 30.

School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.

Evidence from other species justifies the hypotheses that useful hybrid vigour occurs in dogs and that it can be exploited for improved health, welfare and fitness for purpose. Unfortunately, most of the relevant published canine studies do not provide estimates of actual hybrid vigour because of inadequate specification of the parentage of mixed-bred dogs. To our knowledge, only three published studies have shed any light on actual hybrid vigour in dogs. There are two reports of actual hybrid vigour between Labrador and Golden retrievers, the first ranging from +2.5% to -6.0% for components of a standardised applied-stimulus behavioural test, and the second being at least +12.4% for chance of graduating as a guide dog. The third study provides a minimum estimate of negative actual hybrid vigour: crossbreds between Labrador retrievers and poodles had a higher prevalence of multifocal retinal dysplasia than the average prevalence in their purebred parent breeds. The lack of estimates of actual hybrid vigour can be overcome by including the exact nature of the cross (e.g. F1, F2 or backcross) and their purebred parental breeds in the specification of mixed-bred dogs. Even if only F1 crossbreds can be categorised, this change would enable researchers to conduct substantial investigations to determine whether hybrid vigour has any utility for dog breeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2016.05.013DOI Listing
August 2016

Canine hip dysplasia - towards more effective selection.

N Z Vet J 2015 Mar 27;63(2):67-8. Epub 2015 Jan 27.

a Faculty of Veterinary Science , University of Sydney , NSW 2006 , Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00480169.2015.985562DOI Listing
March 2015

The sheep genome illuminates biology of the rumen and lipid metabolism.

Science 2014 Jun;344(6188):1168-1173

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1252806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157056PMC
June 2014

Mutation discovery for Mendelian traits in non-laboratory animals: a review of achievements up to 2012.

Anim Genet 2014 Apr 26;45(2):157-70. Epub 2013 Dec 26.

Faculty of Veterinary Science, University of Sydney, Sydney, NSW, 2006, Australia.

Within two years of the re-discovery of Mendelism, Bateson and Saunders had described six traits in non-laboratory animals (five in chickens and one in cattle) that show single-locus (Mendelian) inheritance. In the ensuing decades, much progress was made in documenting an ever-increasing number of such traits. In 1987 came the first discovery of a causal mutation for a Mendelian trait in non-laboratory animals: a non-sense mutation in the thyroglobulin gene (TG), causing familial goitre in cattle. In the years that followed, the rate of discovery of causal mutations increased, aided mightily by the creation of genome-wide microsatellite maps in the 1990s and even more mightily by genome assemblies and single-nucleotide polymorphism (SNP) chips in the 2000s. With sequencing costs decreasing rapidly, by 2012 causal mutations were being discovered in non-laboratory animals at a rate of more than one per week. By the end of 2012, the total number of Mendelian traits in non-laboratory animals with known causal mutations had reached 499, which was half the number of published single-locus (Mendelian) traits in those species. The distribution of types of mutations documented in non-laboratory animals is fairly similar to that in humans, with almost half being missense or non-sense mutations. The ratio of missense to non-sense mutations in non-laboratory animals to the end of 2012 was 193:78. The fraction of non-sense mutations (78/271 = 0.29) was not very different from the fraction of non-stop codons that are just one base substitution away from a stop codon (21/61 = 0.34).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/age.12103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225684PMC
April 2014

Genetic correlations among canine hip dysplasia radiographic traits in a cohort of Australian German Shepherd Dogs, and implications for the design of a more effective genetic control program.

PLoS One 2013 7;8(11):e78929. Epub 2013 Nov 7.

Faculty of Veterinary Science, The University of Sydney, Sydney, New South Wales, Australia.

Canine hip dysplasia (CHD) is a common musculoskeletal disease in pedigree dog populations. It can cause severe pain and dysfunction which may require extensive medication and/or surgical treatment and often ultimately requires humane euthanasia. CHD has been found to be moderately heritable and, given its impact on welfare, should be considered an imperative breeding priority. The British Veterinary Association/Kennel Club scoring method is one of several measures used to assess the genetic propensity of potential breeding stock for dysplastic changes to the hips based on radiographic examination. It is a complex measure composed of nine ordinal traits, intended to evaluate both early and late dysplastic changes. It would be highly desirable if estimated breeding values (EBVs) for these nine traits were consolidated into a simpler, EBV-based, selection index more easily usable by breeders. A multivariate analysis on the phenotype scores from an Australian cohort of 13,124 German Shepherd Dogs (GSDs) returned genetic correlations between 0.48-0.97 for the nine traits which fell into two trait groups, Group 1 reflecting early changes ("laxity") and Group 2 reflecting late changes ("osteoarthritis"). Principal components analysis of the ordinal EBVs suggested the same pattern, with strong differentiation between "laxity" and "osteoarthritis" traits in the second component. Taking account of all results, we recommend interim use of two selection indexes: the first being the average of ordinal EBVs for "laxity" traits and the second being the average of ordinal EBVs for "osteoarthritis" traits. The correlation between these two selection indexes (0.771-0.774) is sufficiently less than unity enabling the selection of dogs with different genetic propensity for laxity and for osteoarthritic CHD changes in GSDs; this may also be applicable in other breeds. Dogs with low propensity for severe osteoarthritic change in the presence of laxity may be of interest both in molecular research and breeding programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078929PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820674PMC
August 2014

Estimated breeding values for canine hip dysplasia radiographic traits in a cohort of Australian German Shepherd dogs.

PLoS One 2013 29;8(10):e77470. Epub 2013 Oct 29.

Faculty of Veterinary Science, The University of Sydney, Sydney, New South Wales, Australia.

Canine hip dysplasia (CHD) is a serious and common musculoskeletal disease of pedigree dogs and therefore represents both an important welfare concern and an imperative breeding priority. The typical heritability estimates for radiographic CHD traits suggest that the accuracy of breeding dog selection could be substantially improved by the use of estimated breeding values (EBVs) in place of selection based on phenotypes of individuals. The British Veterinary Association/Kennel Club scoring method is a complex measure composed of nine bilateral ordinal traits, intended to evaluate both early and late dysplastic changes. However, the ordinal nature of the traits may represent a technical challenge for calculation of EBVs using linear methods. The purpose of the current study was to calculate EBVs of British Veterinary Association/Kennel Club traits in the Australian population of German Shepherd Dogs, using linear (both as individual traits and a summed phenotype), binary and ordinal methods to determine the optimal method for EBV calculation. Ordinal EBVs correlated well with linear EBVs (r = 0.90-0.99) and somewhat well with EBVs for the sum of the individual traits (r = 0.58-0.92). Correlation of ordinal and binary EBVs varied widely (r = 0.24-0.99) depending on the trait and cut-point considered. The ordinal EBVs have increased accuracy (0.48-0.69) of selection compared with accuracies from individual phenotype-based selection (0.40-0.52). Despite the high correlations between linear and ordinal EBVs, the underlying relationship between EBVs calculated by the two methods was not always linear, leading us to suggest that ordinal models should be used wherever possible. As the population of German Shepherd Dogs which was studied was purportedly under selection for the traits studied, we examined the EBVs for evidence of a genetic trend in these traits and found substantial genetic improvement over time. This study suggests the use of ordinal EBVs could increase the rate of genetic improvement in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077470PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812223PMC
August 2014

Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs.

PLoS One 2012 27;7(6):e39620. Epub 2012 Jun 27.

Faculty of Veterinary Science, The University of Sydney, Sydney, New South Wales, Australia.

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039620PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384595PMC
March 2013

A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii).

BMC Genet 2011 Aug 19;12:72. Epub 2011 Aug 19.

Reprogen, Faculty of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia.

Background: The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species.

Results: A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a) sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH), (b) End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c) tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers) to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map.

Conclusions: Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby genome and considerably extends that of the first-generation map. It will be a valuable resource for ongoing tammar wallaby genetic research and assembling the genome sequence. The sex-pooled map is available online at http://compldb.angis.org.au/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2156-12-72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176194PMC
August 2011

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

Genome Biol 2011 Aug 29;12(8):R81. Epub 2011 Aug 29.

The Australian Research Council Centre of Excellence in Kangaroo Genomics, Australia.

Background: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development.

Results: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements.

Conclusions: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/gb-2011-12-8-r81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277949PMC
August 2011

A first-generation integrated tammar wallaby map and its use in creating a tammar wallaby first-generation virtual genome map.

BMC Genomics 2011 Aug 19;12:422. Epub 2011 Aug 19.

Australian Research Council (ARC) Centre of Excellence for Kangaroo Genomics.

Background: The limited (2X) coverage of the tammar wallaby (Macropus eugenii) genome sequence dataset currently presents a challenge for assembly and anchoring onto chromosomes. To provide a framework for this assembly, it would be a great advantage to have a dense map of the tammar wallaby genome. However, only limited mapping data are available for this non-model species, comprising a physical map and a linkage map.

Results: We combined all available tammar wallaby mapping data to create a tammar wallaby integrated map, using the Location DataBase (LDB) strategy. This first-generation integrated map combines all available information from the second-generation tammar wallaby linkage map with 148 loci, and extensive FISH mapping data for 492 loci, especially for genes likely to be located at the ends of wallaby chromosomes or at evolutionary breakpoints inferred from comparative information. For loci whose positions are only approximately known, their location in the integrated map was refined on the basis of comparative information from opossum (Monodelphis domestica) and human. Interpolation of segments from the opossum and human assemblies into the integrated map enabled the subsequent construction of a tammar wallaby first-generation virtual genome map, which comprises 14336 markers, including 13783 genes recruited from opossum and human assemblies. Both maps are freely available at http://compldb.angis.org.au.

Conclusions: The first-generation integrated map and the first-generation virtual genome map provide a backbone for the chromosome assembly of the tammar wallaby genome sequence. For example, 78% of the 10257 gene-scaffolds in the Ensembl annotation of the tammar wallaby genome sequence (including 10522 protein-coding genes) can now be given a chromosome location in the tammar wallaby virtual genome map.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-12-422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170641PMC
August 2011

Response to the documentary Pedigree Dogs Exposed: three reports and their recommendations.

Authors:
Frank W Nicholas

Vet J 2011 Aug 13;189(2):126-8. Epub 2011 Jul 13.

The BBC documentary Pedigree Dogs Exposed precipitated three inquiries into dog breeding and showing in the UK. Recommendations arising from the inquiries have been and are being implemented. The organisation that was most criticised in the documentary, the Kennel Club, responded quickly to address the major issues and has, for the most part, embraced the inquiries' recommendations. When the recommendations are fully implemented, there will have been some major changes in dog breeding and showing, with a far stronger emphasis placed on health and welfare of dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2011.06.007DOI Listing
August 2011

A genealogical survey of Australian registered dog breeds.

Vet J 2011 Aug 7;189(2):203-10. Epub 2011 Jul 7.

Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia.

Breeding practices were analysed for 32 registered dog breeds representing very small registries (120 Central Asian shepherd dogs) through to very large registries (252,521 German shepherd dogs) in Australia. The vast majority (91%) of registered kennels in Australia that were sampled did not regularly employ either close breeding or popular sire usage in their kennels and the weighted mean inbreeding coefficient of Australian pedigree dogs was <5%. Australian breed mean inbreeding coefficients ranged from 0% (Central Asian shepherd dog) to 10.1% (Bichon Frise). Breed effective population sizes ranged from 26 (Ibizan hound) to 1090 (Golden retriever), comparable with other species of domesticated animals. The relatively low levels of inbreeding suggest that pedigree dog disorders are unlikely to arise frequently from the use of popular sires or close breeding in Australian registered dog breeds. It is possible that deleterious allele fixation might be driven by founder effects, genetic drift or adverse selection practices, which were not assessed in this analysis. European popular sire definitions should be revisited for rare breeds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2011.06.020DOI Listing
August 2011

Canine genetics: a very special issue.

Vet J 2011 Aug 6;189(2):123-5. Epub 2011 Jul 6.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2011.06.006DOI Listing
August 2011

Internet resources cataloguing inherited disorders in dogs.

Vet J 2011 Aug 6;189(2):132-5. Epub 2011 Jul 6.

Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia.

Up-to-date annotated catalogues of known inherited disorders in dogs are freely available on the Internet, providing vital information to existing and prospective dog owners, dog breeders, veterinarians, geneticists and others interested in the occurrence and control of inherited disorders. These resources are the Canine Inherited Disorders Database (CIDD), Inherited Diseases in Dogs (IDID) and Online Mendelian Inheritance in Animals (OMIA) the latter associated with Listing of Inherited Disorders in Animals (LIDA). The history and features of these resources are summarised.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2011.06.009DOI Listing
August 2011

Selection against canine hip dysplasia: success or failure?

Vet J 2011 Aug 2;189(2):160-8. Epub 2011 Jul 2.

Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia.

Canine hip dysplasia (CHD) is a multifactorial skeletal disorder which is very common in pedigree dogs and represents a huge concern for canine welfare. Control schemes based on selective breeding have been in operation for decades. The aim of these schemes is to reduce the impact of CHD on canine welfare by selecting for reduced radiographic evidence of CHD pathology as assessed by a variety of phenotypes. There is less information regarding the genotypic correlation between these phenotypes and the impact of CHD on canine welfare. Although the phenotypes chosen as the basis for these control schemes have displayed heritable phenotypic variation in many studies, success in achieving improvement in the phenotypes has been mixed. There is significant room for improvement in the current schemes through the use of estimated breeding values (EBVs), which can combine a dog's CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are proven to be genetically correlated with CHD (especially elbow dysplasia phenotypes), and information from genetic tests for population-relevant DNA markers, as such tests become available. Additionally, breed clubs should be encouraged and assisted to formulate rational, evidenced-based breeding recommendations for CHD which suit their individual circumstances and dynamically to adjust the breeding recommendations based on continuous tracking of CHD genetic trends. These improvements can assist in safely and effectively reducing the impact of CHD on pedigree dog welfare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2011.06.014DOI Listing
August 2011

Assignment of chromosomal locations for unassigned SNPs/scaffolds based on pair-wise linkage disequilibrium estimates.

BMC Bioinformatics 2010 Apr 7;11:171. Epub 2010 Apr 7.

Reprogen-Animal Bioscience, Faculty of Veterinary Science, University of Sydney, Camden NSW 2570, Australia.

Background: Recent developments of high-density SNP chips across a number of species require accurate genetic maps. Despite rapid advances in genome sequence assembly and availability of a number of tools for creating genetic maps, the exact genome location for a number of SNPs from these SNP chips still remains unknown. We have developed a locus ordering procedure based on linkage disequilibrium (LODE) which provides estimation of the chromosomal positions of unaligned SNPs and scaffolds. It also provides an alternative means for verification of genetic maps. We exemplified LODE in cattle.

Results: The utility of the LODE procedure was demonstrated using data from 1,943 bulls genotyped for 73,569 SNPs across three different SNP chips. First, the utility of the procedure was tested by analysing the masked positions of 1,500 randomly-chosen SNPs with known locations (50 from each chromosome), representing three classes of minor allele frequencies (MAF), namely >0.05, 0.01
Conclusion: The LODE procedure described in this study is an efficient and accurate method for positioning SNPs (MAF>0.05), for validating and checking the quality of a genome assembly, and offers a means for positioning of unordered scaffolds containing SNPs. The LODE procedure will be helpful in refining genome sequence assemblies, especially those being created from next-generation sequencing where high-throughput SNP discovery and genotyping platforms are integrated components of genome analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-11-171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859757PMC
April 2010

Disorders in pedigree dogs: assembling the evidence.

Vet J 2010 Jan 5;183(1):8-9. Epub 2009 Dec 5.

Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2009.11.008DOI Listing
January 2010

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

Science 2009 Apr;324(5926):522-8

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1169588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200PMC
April 2009

Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage map and QTL for growth rate and body weight.

Genet Sel Evol 2009 Apr 24;41:34. Epub 2009 Apr 24.

ReproGen--Advanced Technologies in Animal Genetics and Reproduction, Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia.

A male sheep linkage map comprising 191 microsatellites was generated from a single family of 510 Awassi-Merino backcross progeny. Except for ovine chromosomes 1, 2, 10 and 17, all other chromosomes yielded a LOD score difference greater than 3.0 between the best and second-best map order. The map is on average 11% longer than the Sheep Linkage Map v4.7 male-specific map. This map was employed in quantitative trait loci (QTL) analyses on body-weight and growth-rate traits between birth and 98 weeks of age. A custom maximum likelihood program was developed to map QTL in half-sib families for non-inbred strains (QTL-MLE) and is freely available on request. The new analysis package offers the advantage of enabling QTL x fixed effect interactions to be included in the model. Fifty-four putative QTL were identified on nine chromosomes. Significant QTL with sex-specific effects (i.e. QTL x sex interaction) in the range of 0.4 to 0.7 SD were found on ovine chromosomes 1, 3, 6, 11, 21, 23, 24 and 26.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1297-9686-41-34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686678PMC
April 2009

A genome wide survey of SNP variation reveals the genetic structure of sheep breeds.

PLoS One 2009 3;4(3):e4668. Epub 2009 Mar 3.

CSIRO Livestock Industries, St Lucia, Brisbane, Queensland, Australia.

The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0004668PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652362PMC
May 2009

Extent of genome-wide linkage disequilibrium in Australian Holstein-Friesian cattle based on a high-density SNP panel.

BMC Genomics 2008 Apr 24;9:187. Epub 2008 Apr 24.

Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), University of Sydney, Camden, NSW 2570, Australia.

Background: The extent of linkage disequilibrium (LD) within a population determines the number of markers that will be required for successful association mapping and marker-assisted selection. Most studies on LD in cattle reported to date are based on microsatellite markers or small numbers of single nucleotide polymorphisms (SNPs) covering one or only a few chromosomes. This is the first comprehensive study on the extent of LD in cattle by analyzing data on 1,546 Holstein-Friesian bulls genotyped for 15,036 SNP markers covering all regions of all autosomes. Furthermore, most studies in cattle have used relatively small sample sizes and, consequently, may have had biased estimates of measures commonly used to describe LD. We examine minimum sample sizes required to estimate LD without bias and loss in accuracy. Finally, relatively little information is available on comparative LD structures including other mammalian species such as human and mouse, and we compare LD structure in cattle with public-domain data from both human and mouse.

Results: We computed three LD estimates, D', Dvol and r2, for 1,566,890 syntenic SNP pairs and a sample of 365,400 non-syntenic pairs. Mean D' is 0.189 among syntenic SNPs, and 0.105 among non-syntenic SNPs; mean r2 is 0.024 among syntenic SNPs and 0.0032 among non-syntenic SNPs. All three measures of LD for syntenic pairs decline with distance; the decline is much steeper for r2 than for D' and Dvol. The value of D' and Dvol are quite similar. Significant LD in cattle extends to 40 kb (when estimated as r2) and 8.2 Mb (when estimated as D'). The mean values for LD at large physical distances are close to those for non-syntenic SNPs. Minor allelic frequency threshold affects the distribution and extent of LD. For unbiased and accurate estimates of LD across marker intervals spanning < 1 kb to > 50 Mb, minimum sample sizes of 400 (for D') and 75 (for r2) are required. The bias due to small samples sizes increases with inter-marker interval. LD in cattle is much less extensive than in a mouse population created from crossing inbred lines, and more extensive than in humans.

Conclusion: For association mapping in Holstein-Friesian cattle, for a given design, at least one SNP is required for each 40 kb, giving a total requirement of at least 75,000 SNPs for a low power whole-genome scan (median r2 > 0.19) and up to 300,000 markers at 10 kb intervals for a high power genome scan (median r2 > 0.62). For estimation of LD by D' and Dvol with sufficient precision, a sample size of at least 400 is required, whereas for r2 a minimum sample of 75 is adequate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-9-187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386485PMC
April 2008

Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN.

Mamm Genome 2007 Nov 22;18(11):808-14. Epub 2007 Oct 22.

ReproGen, The University of Sydney, PMB3, Camden, New South Wales 2570, Australia.

Bulldog dwarfism in Dexter cattle is one of the earliest single-locus disorders described in animals. Affected fetuses display extreme disproportionate dwarfism, reflecting abnormal cartilage development (chondrodysplasia). Typically, they die around the seventh month of gestation, precipitating a natural abortion. Heterozygotes show a milder form of dwarfism, most noticeably having shorter legs. Homozygosity mapping in candidate regions in a small Dexter pedigree suggested aggrecan (ACAN) as the most likely candidate gene. Mutation screening revealed a 4-bp insertion in exon 11 (2266_2267insGGCA) (called BD1 for diagnostic testing) and a second, rarer transition in exon 1 (-198C>T) (called BD2) that cosegregate with the disorder. In chondrocytes from cattle heterozygous for the insertion, mutant mRNA is subject to nonsense-mediated decay, showing only 8% of normal expression. Genotyping in Dexter families throughout the world shows a one-to-one correspondence between genotype and phenotype at this locus. The heterozygous and homozygous-affected Dexter cattle could prove invaluable as a model for human disorders caused by mutations in ACAN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00335-007-9066-9DOI Listing
November 2007

A physical map of the bovine genome.

Genome Biol 2007 ;8(8):R165

USDA, ARS, US Meat Animal Research Center, Clay Center, NE 68933, USA.

Background: Cattle are important agriculturally and relevant as a model organism. Previously described genetic and radiation hybrid (RH) maps of the bovine genome have been used to identify genomic regions and genes affecting specific traits. Application of these maps to identify influential genetic polymorphisms will be enhanced by integration with each other and with bacterial artificial chromosome (BAC) libraries. The BAC libraries and clone maps are essential for the hybrid clone-by-clone/whole-genome shotgun sequencing approach taken by the bovine genome sequencing project.

Results: A bovine BAC map was constructed with HindIII restriction digest fragments of 290,797 BAC clones from animals of three different breeds. Comparative mapping of 422,522 BAC end sequences assisted with BAC map ordering and assembly. Genotypes and pedigree from two genetic maps and marker scores from three whole-genome RH panels were consolidated on a 17,254-marker composite map. Sequence similarity allowed integrating the BAC and composite maps with the bovine draft assembly (Btau3.1), establishing a comprehensive resource describing the bovine genome. Agreement between the marker and BAC maps and the draft assembly is high, although discrepancies exist. The composite and BAC maps are more similar than either is to the draft assembly.

Conclusion: Further refinement of the maps and greater integration into the genome assembly process may contribute to a high quality assembly. The maps provide resources to associate phenotypic variation with underlying genomic variation, and are crucial resources for understanding the biology underpinning this important ruminant species so closely associated with humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/gb-2007-8-8-r165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374996PMC
February 2008

A comparative location database (CompLDB): map integration within and between species.

Mamm Genome 2007 May 23;18(5):287-99. Epub 2007 Jun 23.

Reprogen, Faculty of Veterinary Science, University of Sydney, B19, New South Wales 2006, Australia.

We have adapted the Location Database (LDB) map-integration strategy of Morton et al. [Ann Hum Genet 56:223-232] (1992) as above to create an integrated map for each of several species for which fully annotated genome sequences are not yet available (sheep, cattle, pig, wallaby), using all types of partial maps for that species, including cytogenetic, linkage, somatic-cell hybrid, and radiation hybrid maps. An integrated map provides not only predictions of the kilobase location of every locus, but also predicts locations (in cM) and cytogenetic band locations for every locus. In this way a comprehensive linkage map and a comprehensive cytogenetic map are created, including all loci, irrespective of whether they have ever been linkage mapped or physically mapped, respectively. High-resolution physical maps from annotated sequenced species have also been placed alongside the integrated maps. This has created a powerful tool for comparative genomics. The LDB map-integration strategy has been extended to make use of zoo-FISH comparative information. It has also been extended to enable the creation of a "virtual" map for each species not yet sequenced by using mapping data from fully sequenced species. All of the partial maps, together with the integrated map, for each species have been placed in a database called Comparative Location Database (CompLDB), which is available for querying, browsing, or download in tabular form at http://medvet.angis.org.au/ldb/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00335-007-9020-xDOI Listing
May 2007
-->