BoneQTL: Selectable markers for bone strength for the poultry industry

Bone fractures and other forms of skeletal damage are a major welfare problem in laying hens. Osteoporosis is a major contributory factor in the problem. It results in a progressive loss of structural bone over the egg laying period, rendering the bones more fragile and consequently more susceptible to fracture. A long-running programme of work at Roslin on laying hen osteoporosis has established the causes of the problem and studied factors influencing its occurrence. Exercise resulting from housing birds in enriched cages or other alternative systems can delay the onset of osteoporosis but fracture rates still remain high because of the more damaging impacts birds can have with perches and other environmental components. Good nutrition has a small effect in lessening the severity of osteoporosis but cannot prevent it. Genetics has the largest influence on osteoporosis and a breeding programme at Roslin based on divergent selection using a bone index comprising key bone indicators has resulted after 9 generations in a line of hens with over 50% greater bone strength. This improvement is additive to nutritional and environmental effects so this genetic approach should decrease fracture incidences in all husbandry systems. The experimental selection has been based on retrospective selection of progeny after post mortem analysis of dams at end of lay. It is time-consuming and not appropriate for large-scale commercial selection. Dead chickens can not reproduce! A system based on marker assisted selection (MAS) would be much more efficient. Studies on an F2 backcross between the divergently selected lines have identified a strong quantitative trait locus (QTL) for the bone index on chromosome 1. A related gene expression comparison identified genes associated with bone and cartilage development within the region of the QTL. The new project will identify functional single nucleotide polymorphisms (SNPs) within the region of the QTL, which can be used to select for improved bone quality in commercial birds.. The ultimate output of the project will be markers that can be used in MAS strategies for breeding laying hens and other types of poultry that have improved resistance to skeletal damage. Furthermore this will demonstrate that the approach can deliver a useable marker which can be extended for other QTL regions. The study will also identify candidate genes or regions controlling the genes and take the first steps to understanding how these genes influence variation in bone strength.

The research programme will fine-map a previosuly identifed QTL and provide selectable markers for bone quality to the poultry industry. The research programme aims to unravel the genetic basis of the QTL and suggest functional mecahnisms from DNA variation to variation in bone strength. The project also aims to identify additonal genomic regions affecting bone quality for future exploitation by the breeding industry. The project will have the following components: 1) High density SNP genotypes using the Illumina BeadXpress in the region of a previously identified QTL on chromosome 1 and lower density across the remainder of the genome. This will be done in the original F2 cross as well as in the founder population of the commercial chickens. 2) High throughput targeted re-sequencing in the regions of identified candidate genes to identify potential causative mutations. Re-sequencing of individuals from divergent selection lines (for bone strength) will further refine the haplotypes identified under Step 1) and identify sequence and structural variation that is present in these haplotypes. 3) To erect hypothesis on the candidate genes and to take suitable steps to test the hypothesis including examining the expression of identified candidates in bone or other tissue to establish their role in the aetiology of variation in bone quality. Birds from the selection lines will be studied further for 'endo-phenotypes' to provide insights in how the DNA variation leads to phenotypic variation. Deliverables: -SNP(s) at or near QTL location(s) that explain variation in bone strength. -Candidate genes and sequence differences that explain variance in bone strength -The location of further QTL which explain additional variation in bone strength for pursuit by industry. -Hypothesis on the function of candidate genes and the observed differences in them in determining bone strength.

There are 16 billion chickens worldwide, producing 78 million tonnes of poultry meat and 58 million tonnes of eggs annually. In Britain, 28.7 million laying hens produce more than 8.6 million eggs per year. Over 30% of laying hens are likely to suffer from bone fracture caused by osteoporosis making this the major welfare challenge in the egg production industry. Our previous work has shown that genetic factors underlie variation in the susceptibility of individual birds to osteoporosis and bone fracture. Recent information suggests that the severity and scale of the problem is getting worse. High incidences of skeletal damage are being reported from birds over the range of husbandry systems now being introduced and it is obvious that the problem is not confined to hens in conventional battery cages. There are sound biological reasons why the problem is getting worse: laying hens are being selected for continuing improvements in egg output and persistency of lay and this is resulting in strains of birds that have decreased opportunity to regenerate structural bone during rest periods in egg production. In consequence, a progressive osteoporosis develops over the laying period that leads to increased bone fragility and susceptibility to fracture. The problem of skeletal damage is thus likely to continue to get worse unless a fundamentally new approach to breeding laying hens is introduced. While some may argue that selection should be eased, the reality is that in a world of reducing resources it is certain that efficiency and cost will continue to be key components of agriculture and will form part of our need to ensure food security. However we should strive for the best welfare that can be achieved for the animals we keep. The current project will provide selectable markers to the poultry industry facilitating Marker Assisted Selection for improved bone strength. Improved bone strength will not only benefit individual bird welfare but also increase the productive life of entire flocks of laying hence and thereby contributing considerable to lower turnover of resources in egg production.