@article{dorshorst_molin_rubin_johansson_stromstedt_pham_chen_hallbook_ashwell_andersson_2011, title={A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken}, volume={7}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1002412}, abstractNote={Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals.}, number={12}, journal={PLOS GENETICS}, author={Dorshorst, Ben and Molin, Anna-Maja and Rubin, Carl-Johan and Johansson, Anna M. and Stromstedt, Lina and Pham, Manh-Hung and Chen, Chih-Feng and Hallbook, Finn and Ashwell, Chris and Andersson, Leif}, year={2011}, month={Dec} }
 @article{dorshorst_okimoto_ashwell_2010, title={Genomic Regions Associated with Dermal Hyperpigmentation, Polydactyly and Other Morphological Traits in the Silkie Chicken}, volume={101}, ISSN={["0022-1503"]}, DOI={10.1093/jhered/esp120}, abstractNote={The Silkie chicken has been a model of melanoctye precursor and neural crest cell migration and proliferation in the developing embryo due to its extensive hyperpigmentation of dermal and connective tissues. Although previous studies have focused on the distribution and structure of the Silkie's pigment or the general mechanisms by which this phenotype presents itself, the causal genetic variants have not been identified. Classical breeding experiments have determined this trait to be controlled by 2 interacting genes, the sex-linked inhibitor of dermal melanin (Id) and autosomal fibromelanosis (Fm) genes. Genome-wide single nucleotide polymorphism (SNP)-trait association analysis was used to detect genomic regions showing significant association with these pigmentation genes in 2 chicken mapping populations designed to segregate independently for Id and Fm. The SNP showing the highest association with Id was located at 72.3 Mb on chromosome Z and 10.3-13.1 Mb on chromosome 20 showed the highest association with Fm. Prior to this study, the linkage group to which Fm belonged was unknown. Although the primary focus of this study was to identify loci contributing to dermal pigmentation in the Silkie chicken, loci associated with various other morphological traits segregating in these populations were also detected. A single SNP in a highly conserved cis-regulatory region of Sonic Hedgehog was significantly associated with polydactyly (Po). Genomic regions in association with silkie feathering or hookless (h), feathered legs (Pti), vulture hock (V), rose comb (R), and duplex comb (D) were also identified.}, number={3}, journal={JOURNAL OF HEREDITY}, author={Dorshorst, Ben and Okimoto, Ron and Ashwell, Chris}, year={2010}, pages={339–350} }
 @article{dorshorst_siegel_ashwell_2011, title={Genomic regions associated with antibody response to sheep red blood cells in the chicken}, volume={42}, ISSN={["0268-9146"]}, DOI={10.1111/j.1365-2052.2010.02146.x}, abstractNote={Summary F
          1 and F2 populations were generated by crossing two lines of chickens divergently selected from a common founder population for 32 generations for either high or low antibody response 5 days post‐injection of a non‐pathogenic antigen, sheep red blood cells (SRBCs). The number of loci with major effects on day 5 SRBC titers was estimated to be more than 7 in this population. There was a significant association between MHC haplotype and day 5 antibody titers as well as body weight at sexual maturity. A significant difference between reciprocal F2 crosses for both 5‐ and 12‐day antibody titers suggests that sex chromosome and/or parent of origin effects on autosomal loci have an important role in immune response. A single marker‐trait association analysis on 1024 genetic markers and 128 F2 individuals detected 11 genomic regions associated with antibody response traits and 17 regions associated with body weight gain. Several of the genomic regions identified as being associated with antibody response have been described previously, while novel regions associated with antibody response were identified on chromosomes 11 and 24. Based on the lack of overlap of the regions associated with body weight and antibody response, we conclude that while these phenotypes are inversely correlated in the selected lines, they are controlled by distinct genetic loci and may be reflective of intense selection pressure on loci affecting the partitioning of nutrients between the immune system and growth pathways.}, number={3}, journal={ANIMAL GENETICS}, author={Dorshorst, B. J. and Siegel, P. B. and Ashwell, C. M.}, year={2011}, month={Jun}, pages={300–308} }
 @article{dorshorst_ashwell_2009, title={Genetic mapping of the sex-linked barring gene in the chicken}, volume={88}, ISSN={["1525-3171"]}, DOI={10.3382/ps.2009-00134}, abstractNote={The sex-linked barring gene of the chicken (Gallus gallus), first identified in 1908, produces an alternating pattern of white and black bars in the adult plumage. More recent studies have shown that melanocytes in the developing feather follicle of the Barred Plymouth Rock experience premature cell death, whereas initially it was thought that melanocytes remained viable in the region of the feather devoid of pigmentation but were simply inhibited from synthesizing melanin. In an attempt to reconcile these 2 different hypotheses at the molecular level, we have taken a gene mapping approach to isolate the sex-linked barring gene variant. We developed a mapping population consisting of 71 F2 chickens from crossing a single Barred Plymouth Rock female with a White Crested Black Polish male. Existing and novel microsatellite markers located on the chicken chromosome Z were used to genotype all individuals in our mapping population. Single marker association analysis revealed a 2.8-Mb region of the distal q arm of chicken chromosome Z to be significantly associated with the barring phenotype (P<0.001). Further analysis suggests that the causal mutation is located within a 355-kb region showing complete association with the barring phenotype and containing 5 known genes [micro-RNA 31 (miRNA-31), methylthioadenosine phosphorylase (MTAP), cyclin-dependent kinase inhibitor 2B (CDKN2B), tripartite motif 36 (TRIM36), and protein geranylgeranyltransferase type I, beta subunit (PGGT1B)], none of which have a defined role in normal melanocyte function. Although several of these genes or their homologs are known to be involved in processes that could potentially explain the barring phenotype, our results indicate that further work directed at fine-mapping this region is necessary to identify this novel mechanism of melanocyte regulation.}, number={9}, journal={POULTRY SCIENCE}, author={Dorshorst, B. J. and Ashwell, C. M.}, year={2009}, month={Sep} }