Online Mendelian Inheritance in Animals (OMIA): a record of advances in animal genetics, freely available on the Internet for 25 years.

For the last 25 years, Online Mendelian Inheritance in Animals (OMIA) has been providing free global access to an ever-increasing record of discoveries made by animal geneticists around the world. To mark this 25-year milestone, this document provides a brief account (including some pre-history) of how OMIA came to be; some timelines of important discoveries and advances in the genetics of the animal species covered by OMIA, gleaned from the OMIA database; and an analysis of the current state of knowledge regarding likely causal variants of single-locus traits in OMIA species, also gleaned from the OMIA database.

Molecular basis of a new ovine model for human 3M syndrome-2.

BACKGROUND: Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595-9940 ) is a previously reported recessively inherited disorder in Australian Poll Merino/Merino sheep. Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2. Here we report the identification of a likely disease-causing variant and propose an ovine model for human 3M syndrome-2. RESULTS: Eight positional candidate genes were identified among the 39 genes in the approximately 1 Mb interval to which the disease was mapped previously. Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220472248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant. A genotyping assay was developed to genotype 583 animals from the original flock, giving an estimated allele frequency of 5%. CONCLUSIONS: The identification of a likely disease-causing variant resulting in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein has enabled improved breeding management of the implicated flock. The opportunity for an ovine model for human 3M syndrome and ensuing therapeutic research is promising given the availability of carrier ram semen for BCRHS.

Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Merino sheep maps to a 1.1-megabase region on ovine chromosome OAR2.

A genome scan was conducted to map the autosomal recessive lethal disorder brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Poll Merino sheep. The scan involved 10 affected and 27 unaffected animals from a single Poll Merino/Merino sheep flock, which were genotyped with the Illumina Ovine SNP50 BeadChip. Association and homozygosity mapping analyses located the disorder in a region comprising 20 consecutive SNPs spanning 1.1 Mb towards the distal end of chromosome OAR2. All affected animals and none of the unaffected animals were homozygous for the associated haplotype in this region. These results provide the basis for identifying the causative mutation(s) and should enable the development of a DNA test to identify carriers in the Poll Merino sheep population. Understanding the molecular control of BCRHS may provide insight into the fundamental genetic control and regulation of the affected organ systems.

Symmetry of hip dysplasia traits in the German Shepherd Dog in Australia.

Canine hip dysplasia (CHD) is a common and debilitating developmental condition of the canine coxofemoral (hip) joint, exhibiting a multifactorial pattern of inheritance. British Veterinary Association hip traits (BVAHTs) are nine radiographic features of hips used in several countries to ordinally score both the right and left hip of potential breeding candidates to assess their suitability for breeding. The objective of this study was to examine some aspects of the relationship between contralateral scores for each BVAHT in a cohort of 13 124 Australian-registered German Shepherd Dogs. Goodman and Kruskal gamma coefficients of 0.48-0.95 and correlation coefficients of 0.50-0.74 demonstrate that the association between right and left hip scores varies between moderate and strong for BVAHTs. Principal component analysis of scores detected a sizeable left-versus-right effect, a finding supported by symmetry and quasi-symmetry analyses which found that seven of the nine BVAHTs display significant marginal asymmetry. Dogs showing asymmetry for one BVAHT are significantly more likely to display asymmetry at other BVAHTs. When asymmetry is expressed as a binary trait (either symmetrical or asymmetrical), it displays low to moderate heritability. Estimates of genetic correlations between right and left scores are very high for all BVAHTs (>0.945), suggesting right and left scores for each BVAHT are largely determined by the same set of genes. The marginal asymmetries are therefore more likely to be of environmental and non-additive genetic origin. In breeding programmes for CHD, we recommend that scores from both hips be used to estimate breeding values, with a term for side-of-hip included in the model to account for score variation owing to asymmetry.

Population genetics of invasive common carp Cyprinus carpio L. in coastal drainages in eastern Australia.

The common carp Cyprinus carpio introduced in two drainages in eastern Australia are largely descended from European common carp, and in a third drainage they descend largely from East Asian common carp. The partial genetic differentiation among the species in those drainages is consistent with their origins.

Molecular cytogenetics and gene mapping in sheep (Ovis aries, 2n = 54).

The development of a completely annotated sheep genome sequence is a key need for understanding the phylogenetic relationships and genetic diversity among the many different sheep breeds worldwide and for identifying genes controlling economically and physiologically important traits. The ovine genome sequence assembly will be crucial for developing optimized breeding programs based on highly productive, healthy sheep phenotypes that are adapted to modern breeding and production conditions. Scientists and breeders around the globe have been contributing to this goal by generating genomic and cDNA libraries, performing genome-wide and trait-associated analyses of polymorphism, expression analysis, genome sequencing, and by developing virtual and physical comparative maps. The International Sheep Genomics Consortium (ISGC), an informal network of sheep genomics researchers, is playing a major role in coordinating many of these activities. In addition to serving as an essential tool for monitoring chromosome abnormalities in specific sheep populations, ovine molecular cytogenetics provides physical anchors which link and order genome regions, such as sequence contigs, genes and polymorphic DNA markers to ovine chromosomes. Likewise, molecular cytogenetics can contribute to the process of defining evolutionary breakpoints between related species. The selective expansion of the sheep cytogenetic map, using loci to connect maps and identify chromosome bands, can substantially contribute to improving the quality of the annotated sheep genome sequence and will also accelerate its assembly. Furthermore, identifying major morphological chromosome anomalies and micro-rearrangements, such as gene duplications or deletions, that might occur between different sheep breeds and other Ovis species will also be important to understand the diversity of sheep chromosome structure and its implications for cross-breeding. To date, 566 loci have been assigned to specific chromosome regions in sheep and the new cytogenetic map is presented as part of this review. This review will also summarize the current cytogenomic status of the sheep genome, describe current activities in the sheep cytogenomics research sector, and will discuss the cytogenomics data in context with other major sheep genomics projects.

Population genetics and management units of invasive common carp Cyprinus carpio in the Murray-Darling Basin, Australia.

Common carp Cyprinus carpio were introduced into Australia on several occasions and are now the dominant fish in the Murray-Darling Basin (MDB), the continent's largest river system. In this study, variability at 14 microsatellite loci was examined in C. carpio (n = 1037) from 34 sites throughout the major rivers in the MDB, from 3 cultured populations, from Prospect Reservoir in the Sydney Basin and from Lake Sorrell in Tasmania. Consistent with previous studies, assignment testing indicated that the Boolara, Yanco and koi strains of C. carpio are present in the MDB. Unique to this study, however, the Prospect strain was widely distributed throughout the MDB. Significant genetic structuring of populations (Fisher's exact test, AMOVA and distribution of the different strains) amongst the MDB sub-drainages was detected, and was strongly associated with contemporary barriers to dispersal and population history. The distributions of the strains were used to infer the history of introduction and spread of C. carpio in the MDB. Fifteen management units are proposed for control programmes that have high levels of genetic diversity, contain multiple interbreeding strains and show no evidence of founder effects or recent population bottlenecks.

Predicting genetic merit for mastitis and fertility in dairy cattle using genome wide selection and high density SNP screens.

Two novel methods for genome wide selection (GWS) were examined for predicting the genetic merit of animals using SNP information alone. A panel of 1,546 dairy bulls with reliable EBVs was genotyped for 15,380 SNPs that spanned the whole bovine genome. Two complexity reduction methods were used, partial least squares (PLS) and regression using a genetic algorithm (GAR), to find optimal solutions of EBVs against SNP information. Extensive internal cross-validation was used tofind the best predictive models followed by external validation (without direct use of the pedigree or SNP location). Both PLS and GAR provided both accurate fit to the training data set for somatic cell count (SCC) (max r = 0.83) and fertility (max r = 0.88) and showed an accuracy of prediction of r = 0.47 for SCC, and r = 0.72 for fertility. This is the first empirical demonstration that genome wide selection can account for a very high proportion of additive genetic variation in fitness traits whilst exploiting only a small percentage of available SNP information, without use of pedigree or QTL mapping. PLS was computationally more efficient than GAR.

A pedigree-analysis approach to the descriptive epidemiology of autosomal-recessive disorders.

We describe a pedigree-analysis approach to estimating descriptive epidemiological parameters for autosomal-recessive disorders when the ancestral source of the disorder is known. We show that the expected frequency of carriers in a cohort equals the gene contribution of the ancestral source to that cohort, which is equivalent to the direct (additive) genetic relationship of that ancestor to the cohort. Also, the expected incidence of affected foetuses ranges from (1/2)F* to F*, where F* is the mean partial inbreeding coefficient (due to the ancestor) of the cohort. We applied this approach to complex vertebral malformation (CVM) in Holstein-Friesians in Australia, for which the ancestral source is a USA-born bull, Carlin-M Ivanhoe Bell. The estimated frequency of carriers was 2.47% for the 1992-born and 4.44% for the 1997-born cohort of Holstein-Friesian cows in Australia. The estimated incidence of affected foetuses/calves was considerably less than one per thousand, ranging from 0.0024 to 0.0048% for the 1992-born cohort, and from 0.0288 to 0.0576% for the 1997-born cohort. These incidences correspond to expected numbers of affected female foetuses/calves ranging from 2 to 4 for the 1992-born cohort and from 28 to 56 for the 1997-born cohort. This approach is easy to implement using software that is readily available.

Use of diagnostic reports to estimate prevalence and distribution of skeletal lesions in young Thoroughbreds.

Diagnostic reports written to assist stud managers in the sale of young Thoroughbreds have not previously been used as a data source for the study of skeletal lesions. However, analyses of these reports may provide efficient and cost-effective insights into the prevalence and distribution of skeletal lesions within a population. Diagnostic reports written by veterinarians were acquired from Thoroughbred stud managers in Australia and New Zealand. The reports were based on approximately 1300 sets of weanling and yearling radiographs taken between 2002 and 2007. The prevalence and anatomical distribution of skeletal lesions in weanlings (299 horses) and yearlings (1004 horses) were determined from these reports. Overall, 69.9% of weanlings and 64.5% of yearlings were reported as having one or more skeletal lesions. Diagnostic reports in weanlings were a strong indication of what was likely to be seen in subsequent yearling reports. These diagnostic reports are typically used by stud managers in the sales process and the potential drawback is that some categories of skeletal lesions may be under-reported. However, there was substantial agreement between the prevalence and distribution of several skeletal lesions reported in this study and those previously reported from direct evaluation of radiographs for Australian and New Zealand Thoroughbred yearlings. Strong agreement was found for osteophytes, enthesiophytes and other modelling in the hocks, and for lesions in the hind fetlocks and stifles. This indicates that written diagnostic reports are a useful and a reliable source of data for the study of some skeletal lesions in young Thoroughbred horses.

P element transposition contributes substantial new variation for a quantitative trait in Drosophila melanogaster.

The P-M system of transposition in Drosophila melanogaster is a powerful mutator for many visible and lethal loci. Experiments using crosses between unrelated P and M stocks to assess the importance of transposition-mediated mutations affecting quantitative loci and response to selection have yielded unrepeatable or ambiguous results. In a different approach, we have used a P stock produced by microinjection of the ry506 M stock. Selection responses were compared between transposition lines that were initiated by crossing M strain females with males from the "co-isogenic" P strain, and ry506 M control lines. Unlike previous attempts to quantify the effects of P element transposition, there is no possibility of P transposition in the controls. During 10 generations of selection for the quantitative trait abdominal bristle number, none of the four control lines showed any response to selection, indicative of isogenicity for those loci affecting abdominal bristle number. In contrast, three of the four transposition lines showed substantial response, with regression of cumulative response on cumulative selection differential ranging from 15% to 25%. Transposition of P elements has produced new additive genetic variance at a rate which is more than 30 times greater than the rate expected from spontaneous mutation.

The prevalence of feline A/B blood types in the Sydney region.

OBJECTIVE: To determine the distribution of A/B blood types in pedigree and crossbred cats in the Sydney region, and to estimate the associated risk of administering incompatible blood in an unmatched random transfusion. DESIGN: A prospective/retrospective study of blood specimens collected from both sick and healthy cats. MATERIALS AND METHODS: Blood was collected from 355 cats from the Sydney region over a 12-year period from 1992 to 2003. Specimens were obtained from 187 domestic crossbred cats (short and long-haired) and 168 pedigree cats. The blood type of each cat was determined by one of three different laboratories using standard methods that varied over the duration of the survey. RESULTS: The distributions of blood types obtained by the three laboratories were not significantly different. The prevalence of type-A, type-B and type-AB blood types in crossbred cats was 62%, 36% and 1.6%, respectively. This is the highest percentage of type-B cats so far reported for an outbred population of domestic cats, and is significantly higher than the 26% reported previously for cats in the Brisbane region. The calculated frequency for the type-B allele assuming Hardy-Weinberg equilibrium for this feline population is 0.60; the corresponding frequency of the type-A allele is thus approximately 0.40. The calculated proportion of random transfusions from this population giving rise to an incompatible blood transfusion is 46%, with half of these being life-threatening events. The calculated proportion of random matings from this population at risk for developing neonatal isoerythrolysis is 23%. The distribution of A and B blood types for pedigree cats was in general agreement with data reported previously for cats in North America and Europe, suggesting that the distribution of blood types in these purebred populations is relatively consistent throughout the world. CONCLUSIONS: The prevalence of type B cats in the owned domestic and pedigree cat population is so high that blood typing or cross matching prior to transfusion should be mandatory, except in Siamese/Oriental cats.

Neuronal ceroid lipofuscinosis in Australian Merino sheep: a new animal model.

In 1997, neuronal ceroid lipofuscinosis (NCL) was identified for the first time in Merino sheep in Australia. A homozygosity mapping approach localized the disease gene in Merino sheep to the same region on chromosome 7 in which NCL was recently mapped in South Hampshire sheep. This region shows conserved synteny with the region on human chromosome 15 in which the human late infantile NCL variant CLN6 was mapped. NCL in Merino and South Hampshire sheep are therefore potential animal models for the human late infantile variant CLN6.

Class I antigens of the bovine major histocompatibility system and resistance to the cattle tick (Boophilus microplus) assessed in three different seasons.

Two consecutive calf crops consisting of 141 three-quarters Brahman/one-quarter Shorthorn cattle were assessed for resistance to the Australian cattle tick Boophilus microplus in May, July and October 1983. Although the level of expressed resistance to artificial infestation varied considerably between seasons, the animals maintained very similar rankings for resistance in all three seasons, and the repeatability of tick resistance ranged from 0.59 to 0.82. The cattle were typed for 30 bovine class I lymphocyte antigens. Antigens W6 and CA31 were associated with susceptibility to artificial tick infestation but none of the other lymphocyte antigens showed strong associations with resistance or susceptibility.

The relationships among ecto- and endoparasite levels, class I antigens of the bovine major histocompatibility system, immunoglobulin E levels and weight gain.

Natural infestations of the cattle tick Boophilus microplus, levels of the buffalo fly Haematobia irritants exigua and faecal nematode egg concentrations (Bunostomum phlebotomum, Cooperia spp., Haemonchus placei, Oesophagostomum radiatum and Trichostrongylus axei) were assessed in 221 Belmont Red calves during the post-weaning period, when the animals were between 9 and 18 months of age. In addition, the 98 males of this group were challenged with B. microplus larvae on two separate occasions. There were strong positive correlations among replicate assessments of the same parasite. Field tick counts and tick counts following deliberate challenge were strongly correlated, and both showed negative correlations with post-weaning weight gain. There was a weak positive correlation between buffalo fly counts and post-weaning weight gain. There was a negative correlation between total worm egg count and weight gain. Among worm species, only the effect of O. radiatum on weight gain was significant. Cattle with bovine major histocompatibility (BoLA) antigens W6.1 and W7 had significantly fewer ticks than cattle lacking these antigens. Cattle with BoLA antigens W7 and CA36 had lower concentrations of nematode eggs in their faeces than cattle lacking these BoLA antigens.

Canine fucosidosis: a biochemical and genetic investigation.

Plasma and leucocytes from six springer spaniels with clinical signs of fucosidosis had low activities of alpha-L-fucosidase. Fucosidase activities in plasma and leucocytes from parents of springers with fucosidosis were approximately half those in non-springer dogs. Examination of pedigree information in relation to classifications based upon plasma and leucocyte assays provided convincing evidence that fucosidosis is inherited in an autosomal recessive manner and that it is possible to detect heterozygotes using plasma and leucocyte assays.

Genetic databases: online catalogues of inherited disorders.

Current information on inherited disorders in domestic animals is available on the internet: Online Mendelian inheritance in animals (OMIA) and Mendelian inheritance in sheep (MIS) are the two major sources of information. OMIA was created (and is maintained) by workers at the University of Sydney. MIS has been compiled by the Committee on Genetic Nomenclature of Sheep and Goats (COGNOSAG), an international group of geneticists. In the future, similar catalogues for other species (starting with goats and cattle) will be made available by COGNOSAG. Electronic access to this information is freely accessible on the world-wide web at http:/(/)www.angis.su.oz.au/Databases/BIRX/om ia (for OMIA), http:/(/)probe.nalusda.gov:8300/animal/omia.h tml (for OMIA in the United States of America) and at http:/(/)www.angis.org.au/Databases/BIRX/mis (for MIS).

Inherited disorders: the comparative picture.

When confronted with a novel familial disorder, veterinarians should consult McKusick's catalogue of inherited disorders in humans, called Mendelian Inheritance in Man (MIM), or its online version (OMIM), to see whether a similar disorder has been reported in humans. They should also consult the other readily available sources of comparative information on mice and domesticated species. Increasingly, such consultations can be conducted on the Internet via the World Wide Web. If it is thought that an animal disorder is homologous with a human disorder, publications describing the animal disorder should include the MIM number(s) for that disorder. Future research can then test the hypothesis of homology, until a consensus is reached.