Sex Differences in Response to Marek's Disease: Mapping Quantitative Trait Loci Regions (QTLRs) to the Z Chromosome.

Marek's Disease (MD) has a significant impact on both the global poultry economy and animal welfare. The disease pathology can include neurological damage and tumour formation. Sexual dimorphism in immunity and known higher susceptibility of females to MD makes the chicken Z chromosome (GGZ) a particularly attractive target to study the chicken MD response. Previously, we used a Hy-Line F6 population from a full-sib advanced intercross line to map MD QTL regions (QTLRs) on all chicken autosomes. Here, we mapped MD QTLRs on GGZ in the previously utilized F6 population with individual genotypes and phenotypes, and in eight elite commercial egg production lines with daughter-tested sires and selective DNA pooling (SDP). Four MD QTLRs were found from each analysis. Some of these QTLRs overlap regions from previous reports. All QTLRs were tested by individuals from the same eight lines used in the SDP and genotyped with markers located within and around the QTLRs. All QTLRs were confirmed. The results exemplify the complexity of MD resistance in chickens and the complex distribution of p-values and Linkage Disequilibrium (LD) pattern and their effect on localization of the causative elements. Considering the fragments and interdigitated LD blocks while using LD to aid localization of causative elements, one must look beyond the non-significant markers, for possible distant markers and blocks in high LD with the significant block. The QTLRs found here may explain at least part of the gender differences in MD tolerance, and provide targets for mitigating the effects of MD.

Mapping QTL Associated with Resistance to Avian Oncogenic Marek's Disease Virus (MDV) Reveals Major Candidate Genes and Variants.

Marek's disease (MD) represents a significant global economic and animal welfare issue. Marek's disease virus (MDV) is a highly contagious oncogenic and highly immune-suppressive α-herpes virus, which infects chickens, causing neurological effects and tumour formation. Though partially controlled by vaccination, MD continues to have a profound impact on animal health and on the poultry industry. Genetic selection provides an alternative and complementary method to vaccination. However, even after years of study, the genetic mechanisms underlying resistance to MDV remain poorly understood. The Major Histocompatability Complex (MHC) is known to play a role in disease resistance, along with a handful of other non-MHC genes. In this study, one of the largest to date, we used a multi-facetted approach to identify QTL regions (QTLR) influencing resistance to MDV, including an F6 population from a full-sib advanced intercross line (FSIL) between two elite commercial layer lines differing in resistance to MDV, RNA-seq information from virus challenged chicks, and genome wide association study (GWAS) from multiple commercial lines. Candidate genomic elements residing in the QTLR were further tested for association with offspring mortality in the face of MDV challenge in eight pure lines of elite egg-layer birds. Thirty-eight QTLR were found on 19 chicken chromosomes. Candidate genes, miRNAs, lncRNAs and potentially functional mutations were identified in these regions. Association tests were carried out in 26 of the QTLR, using eight pure lines of elite egg-layer birds. Numerous candidate genomic elements were strongly associated with MD resistance. Genomic regions significantly associated with resistance to MDV were mapped and candidate genes identified. Various QTLR elements were shown to have a strong genetic association with resistance. These results provide a large number of significant targets for mitigating the effects of MDV infection on both poultry health and the economy, whether by means of selective breeding, improved vaccine design, or gene-editing technologies.

Mapping Ethanol Tolerance in Budding Yeast Reveals High Genetic Variation in a Wild Isolate.

Ethanol tolerance, a polygenic trait of the yeast Saccharomyces cerevisiae, is the primary factor determining industrial bioethanol productivity. Until now, genomic elements affecting ethanol tolerance have been mapped only at low resolution, hindering their identification. Here, we explore the genetic architecture of ethanol tolerance, in the F6 generation of an Advanced Intercrossed Line (AIL) mapping population between two phylogenetically distinct, but phenotypically similar, S. cerevisiae strains (a common laboratory strain and a wild strain isolated from nature). Under ethanol stress, 51 quantitative trait loci (QTLs) affecting growth and 96 QTLs affecting survival, most of them novel, were identified, with high resolution, in some cases to single genes, using a High-Resolution Mapping Package of methodologies that provided high power and high resolution. We confirmed our results experimentally by showing the effects of the novel mapped genes: MOG1, MGS1, and YJR154W. The mapped QTLs explained 34% of phenotypic variation for growth and 72% for survival. High statistical power provided by our analysis allowed detection of many loci with small, but mappable effects, uncovering a novel "quasi-infinitesimal" genetic architecture. These results are striking demonstration of tremendous amounts of hidden genetic variation exposed in crosses between phylogenetically separated strains with similar phenotypes; as opposed to the more common design where strains with distinct phenotypes are crossed. Our findings suggest that ethanol tolerance is under natural evolutionary fitness-selection for an optimum phenotype that would tend to eliminate alleles of large effect. The study provides a platform for development of superior ethanol-tolerant strains using genome editing or selection.

FABP4 gene has a very large effect on feed efficiency in lactating Israeli Holstein cows.

Improving feed efficiency (FE) is a major goal for the livestock industry. Previously, we have identified 48 SNP markers distributed over 32 genes significantly associated with residual feed intake (RFI) in Israeli Holstein male calves, the most significant of which are located in the bovine FABP4 gene. In the present study, we tested associations of eight of the FABP4 markers with RFI and feed conversion ratio (FCR), along with milk composition and feeding behavioral traits, in 114 lactating Israeli Holstein cows. Large allele effects were found, along with large contributions of FABP4 markers to the phenotypic variation [mean contribution of all significant markers (P < 0.05), 15.4 and 12.0% for RFI and FCR, respectively] and genotypic variation [means of all significant markers (P < 0.05), 75.7 and 32.4% in RFI and FCR, respectively]. However, the association of all significant FABP4 markers with FE and milk content traits was found in opposite directions, such that improved FE was accompanied by decreased milk content. Hence, before inclusion in breeding programs, the gain in FE must be economically balanced with the loss in milk contents. On the other hand, these findings imply that in any current improvement program concentrated on milk traits alone, without taking into account the effect on FE, the progress in milk composition is probably accompanied by deterioration of FE. These results, if confirmed in other populations and breeds, set FABP4 as a prime candidate in any marker-assisted selection program targeting FE as a whole and RFI in particular.

The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.

FABP4 is a leading candidate gene associated with residual feed intake in growing Holstein calves.

Ecological and economic concerns drive the need to improve feed utilization by domestic animals. Residual feed intake (RFI) is one of the most acceptable measures for feed efficiency (FE). However, phenotyping RFI-related traits is complex and expensive and requires special equipment. Advances in marker technology allow the development of various DNA-based selection tools. To assimilate these technologies for the benefit of RFI-based selection, reliable phenotypic measures are prerequisite. In the current study, we identified single nucleotide polymorphisms (SNPs) associated with RFI phenotypic consistency across different ages and diets (named RFI 1-3), using DNA samples of high or low RFI ranked Holstein calves. Using targeted sequencing of chromosomal regions associated with FE- and RFI-related traits, we identified 48 top SNPs significantly associated with at least one of three defined RFIs. Eleven of these SNPs were harbored by the fatty acid binding protein 4 (FABP4). While 10 significant SNPs found in FABP4 were common for RFI 1 and RFI 3, one SNP (FABP4_5; A

Genome-wide association study for somatic cell score in Valdostana Red Pied cattle breed using pooled DNA.

BACKGROUND: Mastitis is a major disease of dairy cattle occurring in response to environmental exposure to infective agents with a great economic impact on dairy industry. Somatic cell count (SCC) and its log transformation in somatic cell score (SCS) are traits that have been used as indirect measures of resistance to mastitis for decades in selective breeding. A selective DNA pooling (SDP) approach was applied to identify Quantitative Trait Loci (QTL) for SCS in Valdostana Red Pied cattle using the Illumina Bovine HD BeadChip. RESULTS: A total of 171 SNPs reached the genome-wide significance for association with SCS. Fifty-two SNPs were annotated within genes, some of those involved in the immune response to mastitis. On BTAs 1, 2, 3, 4, 9, 13, 15, 17, 21 and 22 the largest number of markers in association to the trait was found. These regions identified novel genomic regions related to mastitis (1-Mb SNP windows) and confirmed those already mapped. The largest number of significant SNPs exceeding the threshold for genome-wide significant signal was found on BTA 15, located at 50.43-51.63 Mb. CONCLUSIONS: The genomic regions identified in this study contribute to a better understanding of the genetic control of the mastitis immune response in cattle and may allow the inclusion of more detailed QTL information in selection programs.

Body composition and reproductive performance at entry into lay of anno 1980 versus anno 2000 broiler breeder females under fast and slow release from feed restriction.

During the 1990s, various disturbances arose affecting broiler breeder females at entry into lay. These disturbances were associated with even slight overfeeding during release of feed restriction in this critical maturation period. The present experiment was carried out to gain some insight into the causes of these disturbances by comparing the effect of fast (FF) and slow (SF) release from feed restriction at entry into lay in 2 broiler breeder populations: B1980, representing the genetic level of 1980, and B2000, the genetic level of 2000. Under the FF treatment, B1980 entered lay 19.2 d earlier than B2000; this increased to 37.4 d earlier under SF. The B1980 population entered lay at virtually the same mean age for SF and FF, whereas B2000 entered lay 15.7 d earlier under the FF. Body weight at first egg were 2,621 g for the B1980 and 3,591 g for B2000. Differences in BW at first egg between feeding treatments within lines were minor. As a percentage of BW, ovary, oviduct, and follicle weights were the same for B1980 and B2000; breast weight was 14.9% for B1980 and 21.2% for B2000; abdominal fat pad weight was 5.37% for B1980 and 2.67% for B2000. Follicle weight and absolute difference in weight between successive follicles was greater in B2000 than in B1980. It is concluded that body fat content does not limit entry into lay, and that threshold BW for onset of sexual maturity of broiler breeder hens increased by about 1,000 g between 1980 and 2000, indicating a tight association between juvenile growth rate and threshold BW for onset of sexual maturity. It is also concluded that disturbances at entry into lay due to overfeeding are not due to smaller differences between successive follicles in B2000 compared with B1980. There are hints, however, that overfeeding may contribute to these disturbances by decreasing differences between successive follicles.

Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis.

Single-gene disorders offer unique opportunities to shed light upon fundamental physiological processes in humans. We investigated an autosomal-recessive phenotype characterized by alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome). By using homozygosity mapping and candidate-gene analysis, we identified a loss-of-function mutation in RBM28, encoding a nucleolar protein. RBM28 yeast ortholog, Nop4p, was previously found to regulate ribosome biogenesis. Accordingly, electron microscopy revealed marked ribosome depletion and structural abnormalities of the rough endoplasmic reticulum in patient cells, ascribing ANE syndrome to the restricted group of inherited disorders associated with ribosomal dysfunction.