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Frank W Nicholas

Publications and source records attributed to Frank W Nicholas.

9 recordsLinked to original sources
PubMed2026

The Animal Variant Classification Guidelines v2: An Update With New Criteria and Improved Clarifications.

The Animal Variant Classification Guidelines (AVCG) were developed to standardize and objectify the classification of putative disease-causing variants. These guidelines are sufficiently reproducible and are used to classify previously published and new disease-causing variants across species. Here, the guidelines are updated (AVCG.v2), based on a three-phase decision process. Overall, four new criteria and seven clarifying comments were added. The number of criteria has increased from 23 to 27, with three new criteria supporting pathogenicity and one new criterion supporting benign classification. Pharmacogenomic variants were determined to fall within the scope of the guidelines. These updated guidelines are being used by the Variant Pathogenicity Working Group (VPWG), part of the Animal Genetic Testing Standardization standing committee, which is a committee of elected members of the International Society for Animal Genetics (ISAG). Under the auspices of ISAG, the VPWG retrospectively classifies published putative disease-causing variants. The pathogenicity label for a variant will be presented in the variant tables of Online Mendelian Inheritance in Animals (OMIA; https://omia.org/). The AVCGv.2 criteria and recommendations were developed by the expertise of the animal genetics community and the ISAG Executive Committee through the Animal Genetics Testing Standardization Committee endorses and strongly encourages their use to evaluate the evidence supporting pathogenicity of putative disease-causing variants.

Animals↗
PubMed2006

Linkage disequilibrium on chromosome 6 in Australian Holstein-Friesian cattle.

We analysed linkage disequilibrium (LD) in Australian Holstein-Friesian cattle by genotyping a sample of 45 bulls for 15 closely-spaced microsatellites on two regions of BTA6 reported to carry important QTL for dairy traits. The order and distance of markers were based on the USDA-MARC linkage map. Frequencies of haplotypes were estimated using the E-M approach and a more computationally-intensive Bayesian approach as implemented in PHASE. LD was then estimated using the Hedrick multiallelic extension of Lewontin normalised coefficient D'. Estimates of D' from the two approaches were in close agreement (r = 0.91). The mean estimates of D' for marker pairs with an inter-marker distance of less than 5 cM (n = 13) are 0.57 and 0.51, and for distances more than 20 cM (n = 44) are 0.29 and 0.17, estimated from the E-M and Bayesian approaches, respectively. The Malecot model was fitted for the exponential decline of LD with map distance between markers. The swept radii (the distance at which LD has declined to 1/e ( approximately 37%) of its initial value) are 11.6 and 13.7 cM for the above two methods, respectively. The Malecot model was also fitted using map distance in Mb from the bovine integrated map (bovine location database, bLDB) in addition to cM from the MARC map. Overall, the results indicate a high level of LD on chromosome 6 in Australian dairy cattle.

Animals↗
PubMed2006

A first-generation metric linkage disequilibrium map of bovine chromosome 6.

We constructed a metric linkage disequilibrium (LD) map of bovine chromosome 6 (BTA6) on the basis of data from 220 SNPs genotyped on 433 Australian dairy bulls. This metric LD map has distances in LD units (LDUs) that are analogous to centimorgans in linkage maps. The LD map of BTA6 has a total length of 8.9 LDUs. Within the LD map, regions of high LD (represented as blocks) and regions of low LD (steps) are observed, when plotted against the integrated map in kilobases. At the most stringent block definition, namely a set of loci with zero LDU increase over the span of these markers, BTA6 comprises 40 blocks, accounting for 41% of the chromosome. At a slightly lower stringency of block definition (a set of loci covering a maximum of 0.2 LDUs on the LD map), up to 81% of BTA6 is spanned by 46 blocks and with 13 steps that are likely to reflect recombination hot spots. The mean swept radius (the distance over which LD is likely to be useful for mapping) is 13.3 Mb, confirming extensive LD in Holstein-Friesian dairy cattle, which makes such populations ideal for whole-genome association studies.

Animals↗
PubMed2006

OMIA (Online Mendelian Inheritance in Animals): an enhanced platform and integration into the Entrez search interface at NCBI.

Online Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited disorders and other familial traits in animals other than humans and mice. Structured as a comparative biology resource, OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible. OMIA is modelled on and is complementary to Online Mendelian Inheritance in Man (OMIM). OMIA has been moved to a MySQL database at the Australian National Genomic Information Service (ANGIS) and can be accessed at http://omia.angis.org.au/. It has also been integrated into the Entrez search interface at the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=omia). Curation of OMIA data by researchers working on particular species and disorders has also been enabled.

Animals↗
PubMed2005

Animal breeding and disease.

Single-locus disorders in domesticated animals were among the first Mendelian traits to be documented after the rediscovery of Mendelism, and to be included in early linkage maps. The use of linkage maps and (increasingly) comparative genomics has been central to the identification of the causative gene for single-locus disorders of considerable practical importance. The 'score-card' in domestic animals is now more than 100 disorders for which the molecular lesion has been identified and hence for which a DNA test is available. Because of the limited lifespan of any such test, a cost-effective and hence popular means of protecting the intellectual property inherent in a DNA test is not to publish the discovery. While understandable, this practice creates a disconcerting precedent. For multifactorial disorders that are scored on an all-or-none basis or into many classes, the effectiveness of control schemes could be greatly enhanced by selection on estimated breeding values for liability. Genetic variation for resistance to pathogens and parasites is ubiquitous. Selection for resistance can therefore be successful. Because of the technical and welfare challenges inherent in the requirement to expose animals to pathogens or parasites in order to be able to select for resistance, there is a very active search for DNA markers for resistance. The first practical fruits of this research were seen in 2002, with the launch of a national scrapie control programme in the UK.

Animal Diseases↗
PubMed2005

Listing of inherited disorders in animals (LIDA): an online relational database, using non-technical descriptions written by veterinary students.

This online database uses a search facility that allows users to select from the 180 recognized dog breeds in Australia and find out which ones are prone to the more than 500 inherited disorders on record. It was developed in consultation with a number of supporting organizations, including the local breeders' governing body and animal-welfare groups, as well as owners. It is hoped that, although primarily for veterinary education, the Web site will increase awareness among breeders and may encourage them to adopt breeding programs that decrease the occurrence of the most prevalent disorders.

Animal Diseases↗
PubMed2004

Development of a highly fecund inbred strain of mice.

A highly fecund inbred mouse line has been established from the Quackenbush Swiss (QS) outbred strain by full-sib inbreeding combined with selection for high number of pups born alive (NBA) and low interlitter interval (ILI). After more than 50 generations of inbreeding and selection, this line, named QSi5, has an NBA of 13.4 and an ILI of 29 days, averaged over the first four parities, and a total productivity of 50.7 NBA. With its exceptional reproductive performance, this line will be very useful in the creation of resources (including advanced intercross lines) for analysis of quantitative trait loci for a wide range of traits, and for the cost-effective creation of congenic lines.

Animals↗
PubMed2003

Online Mendelian Inheritance in Animals (OMIA): a comparative knowledgebase of genetic disorders and other familial traits in non-laboratory animals.

Online Mendelian Inheritance in Animals (OMIA) provides up-to-date information on inherited disorders and other familial traits in non-laboratory animals. It is freely available online at http://www.angis.org.au/omia. With a strong emphasis on comparative biology, OMIA is modelled on, and reciprocally hyperlinked with, Online Mendelian Inheritance in Man (OMIM). It provides a comprehensive catalog of animal models of human inherited disorders, and also provides comprehensive access to information on potential human homologues of inherited disorders and traits in animals. Because its whole structure is based on comparative biology, it provides phenotypic information in a format that is complementary to all the relevant mapping and sequence databases now existing or being created across the animal kingdom.

Animals↗