Ring lethal: an early embryonic failure in medium white turkeys

Ring lethal denotes an early embryonic failure of developing blastoderms in medium white turkeys that can be recognized macroscopically in situ after 48 hours of incubation. The condition is characterized by a white ring of amorphous cells in the area opaca with or without the presence of cells in the area pellucida. The disorder is inherited as an autosomal recessive trait that is expressed in the homozygous condition. Attempts to elucidate the cause of the ring lethal gene's expression have been unsuccessful. The symbol rl is proposed for the gene.     

Blastoderm degeneration, an early embryonic failure in dwarf Single Comb White Leghorn chickens.

Blastoderm degeneration is an early embryonic lethal condition observed in selected paired matings within a line of dwarf Single Comb White Leghorn chickens that results in a 25% reduction of the hatch of fertilized eggs. The disorder is macroscopically evident at 32 h of incubation by the presence of a small localized indentation on the outer periphery of the expanding blastoderm. The affected blastoderms undergo a series of rapid macroscopic degenerative changes that conclude at about 120 h characterized by the presence of dispersed blastoderm fragments on the surface of the egg's yolk. Microscopically, this embryonic failure appears to manifest itself between Hamburger-Hamilton stages 8 and 9 of development and is characterized by a series of retarded developmental processes: closure of the anterior neuropore, brain vesicle differentiation, somite formation, and cardiac development. The disorder is inherited as an autosomal recessive trait. Attempts to identify factors that influence the disorder have thus far been unsuccessful. The symbol bld is proposed for this recessive gene.     

"Trembler"--a nervous disorder in chickens

The trembler chickens, which spontaneously occurred in the Poultry farm of Animal Genetics Laboratory of Nagoya University, showed the phenotypic symptoms as of the tremor of the head, neck and body. Mild symptoms of shaking were observed in most of the day-old affected chicks, but this sign will be kept calm during 1-4 weeks old. Subsequently, trembling became clearly evident. Progressing with age, the trembling severely increased inducing the chickens to walk with a stumbling gait. In the terminal stages the chickens were hardly to stand and die from inanition. Mating experiments between half-sib and sire-daughter have revealed that the responsible gene (tr) for the trembler chicken is an autosomal recessive gene.     

Microphthalmia-4: a sex-influenced inherited eye condition of the chicken.

A new mutation of the chicken that causes a reduction in eyeball size is described. Eyeball size reduction is extreme in over 80% of affected individuals. Two-thirds of affected chickens have bilateral expression, while the rest are unilaterally affected. The trait appears to affect liveability beyond that which might be expected of blind individuals. Embryonic mortality was increased five-fold among microphthalmic individuals, and all but two of the 35 microphthalmic chicks that hatched died within a week. Data from various crosses indicate that this condition is inherited as an autosomal recessive with expression being limited primarily to females. The name microphthalmia-4 and the gene symbol mi-4 are proposed for this trait.     

A missense mutation in TYRP1 causes the chocolate plumage color in chicken and alters melanosome structure

The chocolate plumage color in chickens is due to a sex‐linked recessive mutation, choc, which dilutes eumelanin pigmentation. Because TYRP1 is sex‐linked in chickens, and TYRP1 mutations determine brown coat color in mammals, TYRP1 appeared as the obvious candidate gene for the choc mutation. By combining gene mapping with gene capture, a complete association was identified between the chocolate phenotype and a missense mutation leading to a His214Asn change in the ZnA zinc‐binding domain of the protein. A diagnostic test confirmed complete association by screening 428 non‐chocolate chickens of various origins. This is the first TYRP1 mutation described in the chicken. Electron microscopy analysis showed that melanosomes were more numerous in feather follicles of chocolate chickens but exhibited an abnormal structure characterized by a granular content and an irregular shape. A similar altered morphology was observed on melanosomes of another TYRP1 mutant in birds, the roux mutation of the quail.     

Genomic-scale analysis of Pasteurella multocida gene expression during growth within liver tissue of chickens with fowl cholera

We have recently reported the gene expression profile of Pasteurella multocida during growth in the blood of chickens with fowl cholera. Here we report the gene expression profile of P. multocida during growth in the livers of similarly infected chickens. We compared expression profiles of bacteria harvested from the livers of infected chickens with late-stage fowl cholera with those of bacteria grown in rich medium. Independent analysis of bacterial expression profiles from three individual chickens indicated that 93 P. multocida genes were always differentially expressed during growth in liver tissue. Of these 93 genes, 49 were upregulated and 44 downregulated in the host. Many of the upregulated genes were involved in energy production and conversion (9/49) and carbohydrate transport and metabolism (8/49), and a number of these have been shown to be induced under anaerobic conditions in other species. The downregulated genes were generally of unknown or poorly characterised functions (14/44). Comparison of the differentially regulated gene sets identified for growth in liver with those identified previously for growth in blood allowed the identification of a core set of 13 upregulated and 16 downregulated genes that were differentially regulated in at least five of the six infections studied.     

Suppression of humoral immunity in chickens prevents transient paralysis caused by a herpesvirus

Marek's disease virus (MDV)3 is a highly oncogenic herpesvirus that usually causes visceral lymphomas and lymphoid infiltration of the peripheral nerves in chickens. A relatively rare encephalitic condition, first found in farm flocks and referred to as transient paralysis (TP), is also caused by MDV(1). TP symptoms occur 9 to 11 days after MDV inoculation and range from mild ataxia to profound coma. Most birds recover by 24 to 72 hr after onset of symptoms, although severely affected birds may die within the same time period. Previous studies in this laboratory (2) showed that susceptibility to TP is a recessive trait controlled by major histocompatibility complex (MHC) genes (i.e., B complex genes of chickens). Inbred line G-B1 chickens (B13/B13) are resistant to TP, whereas chickens from related inbred lines G-B2 (B6/B6) and G-B3 (B15/B15) are highly susceptible. In this study chickens were immunosuppressed by neonatal cyclophosphamide (CY) treatment or surgical bursectomy (BX) to determine the possible role of antibodies in the pathogenesis of TP.     

Aneuploidy-Cancer Predisposition Syndromes: A New Link between the Mitotic Spindle Checkpoint and Cancer

Genetic cancer predisposition syndromes have been crucial to the identification of genes and pathways involved in carcinogenesis. Constitutional gene mutations segregating with distinctive cancer phenotypes provide unequivocal evidence of a gene’s causal role in cancer. This type of evidence has been central in proving that oncogenes and tumor suppressor genes can cause human cancers, but has been lacking for genes implicated in generating aneuploidy. However, recently we identified mutations in the mitotic checkpoint gene BUB1B in an autosomal recessive condition characterised by mosaic aneuploidies and childhood cancers. This finding strongly suggests that aneuploidy is causally related to cancer development.     

Influence of triiodothyronine and growth hormone on growth of dwarf and normal chickens: interactions of hormones and genotype

The effects of dietary triiodothyronine (T3), injections of a preparation of growth hormone (GH) (purified from chicken pituitary tissue) and their combination on growth were investigated in three lines of chickens. The three lines were the Cornell K strain (K) (a single Comb White Leghorn strain), the Cornell K strain hemizygous for the sex-linked dwarfing gene (SLD), and the Cornell K strain homozygous recessive for the autosomal dwarfing gene (ADW). A dietary T3 treatment by genotype interaction was observed. Dietary T3 (0.1 ppm) decreased growth in the K line, tended to decrease growth in the ADW line while it tended to increase growth in the SLD line. Chicken growth hormone (100 micrograms/kg body wt) alone did not affect growth in any of the lines studied. There was, however, a GH treatment by T3 treatment interaction. Chicken GH overcame the growth-depressing effects of T3 in the K and ADW lines while it tended to promote growth in T3 treated SLD birds. Dwarf (SLD) chickens had higher basal circulating GH concentrations, lower circulating immunoreactive somatomedin C concentrations, and lower circulating T3 concentrations than the K or ADW chickens.     

Faded shaker, a lethal pigment and neurological mutation in the chicken

Faded shaker (fs) is a lethal condition in chickens resulting in a congenital tremor and a dilution of down and feather melanin. It is inherited as an autosomal recessive gene with the homozygote showing incomplete penetrance, the apparent result of a single dominant gene masking the effects of the fs/fs genotype. Mortality of the mutants occurred between 18 days of incubation and three months of age; most died before one week of age with half of the mutants dying before hatching. No specific cause of death was observed. The tremor had a frequency of 6 to 10 vibrations per second, was more pronounced in the posterior end of the bird and was constant over time within an individual. Weight of the faded shaker cerebellum was reduced by 7.6%, presumably due to an observed deficiency of myelin. The down and feather color of faded shakers ranged from almost normal to near white, but was constant over several feather generations within an individual. Faded shaker melanosomes were both deficient in number and incompletely melanized. Melanocyte dendrition and melanosome distribution were both normal. Skin transplants showed that the dilution was a result of a defect located in the fs/fs skin. Pigmentation of the retinal pigment epithelium also was abnormal.     

The inheritance of fingerprint patterns.

Analysis of the fingerprints of 571 members of the Habbanite isolate suggest inherited patterns and pattern sequences. A genetic theory has been developed; it assumes that the basic fingerprint pattern sequence is all ulnar loops and that a variety of genes cause deviations from this pattern sequence. Genes that have been proposed include: (1) a semidominant gene for whorls on the thumbs (one homozygote has whorls on both thumbs, the other has ulnar loops on both thumbs and the heterozygote usually has two ulnar loops or one ulnar loop and one whorl); (2) a semidominant gene for whorls on the ring fingers which acts like the gene for whorls on the thumbs; (3) a dominant gene for arches on the thumbs and often on other fingers; (4) one or more dominant genes for arches on the fingers; (5) a dominant gene for whorls on all fingers except for an ulnar loop on the middle finger; (6) a dominant gene for radial loops on the index fingers, frequently associated with an arch on the middle fingers; and (7) a recessive gene for radial loops on the ring and little fingers. These genes may act independently or may show epistasis.     

Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci

Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases. Mohammad Mahdi Motazacker and Masoud Garshasbi have contributed equally to this work.     

Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21.

Sclerosteosis is an uncommon, autosomal recessive, progressive, sclerosing, bone dysplasia characterized by generalized osteosclerosis and hyperostosis of the skeleton, affecting mainly the skull and mandible. In most patients this causes facial paralysis and hearing loss. Other features are gigantism and hand abnormalities. In the present study, linkage analysis in two consanguineous families with sclerosteosis resulted in the assignment of the sclerosteosis gene to chromosome 17q12-q21. This region was analyzed because of the recent assignment to this chromosomal region of the gene causing van Buchem disease, a rare autosomal recessive condition with a hyperostosis similar to sclerosteosis. Because of the clinical similarities between sclerosteosis and van Buchem disease, it has previously been suggested that both conditions might be caused by mutations in the same gene. Our study now provides genetic evidence for this hypothesis.     

Shankless, a new mutation on chromosome 2 in the chicken

A mutant condition characterized by absence of shanks is invariably present in chickens that are homokaryotypic for an X-ray-induced pericentric inversion to chromosome 2. The mutation was studied in 260 embryos at 19 days of incubation. Embryos produced from matings of parents with and without the inversion were karyotyped and their skeletons observed and measured. The mutant phenotype, which was seen in all birds homokaryotypic for the inversion, is characterized by malformed and reduced metacarpals, absence of tarsometatarsal shanks, increased tibia length, extra bones in digits two, three, and four, and fusion of proximal phalanges. Heterokaryotypic and homokaryotypic normal embryos had normal phenotypes, but the length of metacarpals was slightly reduced in heterokaryotypes. The primary effect of the mutation is to cause misplacement, malformation, and underdevelopment of metatarsals II, III, and IV. The recessive mutation, located in the proximal region of chromosome 2, has been designated shankless (shl).     

Epigenetic modification of TLRs in leukocytes is associated with increased susceptibility to Salmonella enteritidis in chickens

Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonella enteritidis (S. enteritidis) infection but the molecular mechanism underlying susceptibility to S. enteritidis infection in chicken remains unclear. SPF chickens injected with S. enteritidis were partitioned into two groups, one consisted of those from Salmonella-susceptible chickens (died within 5 d after injection, n = 6), the other consisted of six Salmonella-resistant chickens that survived for 15 d after injection. The present study shows that the bacterial load in susceptible chickens was significantly higher than that in resistant chickens and TLR4, TLR2-1 and TLR21 expression was strongly diminished in the leukocytes of susceptible chickens compared with those of resistant chickens. The induction of expression of pro-inflammatory cytokine genes, IL-6 and IFN-β, was greatly enhanced in the resistant but not in susceptible chickens. Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens. Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1. DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens. Taken together, the results demonstrate that ZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility to S. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21 and TLR2-1.     

Highly pathogenic H5N1 influenza virus causes coagulopathy in chickens

Severe hemorrhage at multiple organs is frequently observed in chickens infected with highly pathogenic avian influenza (HPAI) A viruses. In this study we examined whether HPAI virus infection leads to coagulation disorder in chickens. Pathological examinations showed that the fibrin thrombi were formed in arterioles at the lung, associated with the viral antigens in endothelial cells of chickens infected intravenously with HPAI virus. Hematological analyses of peripheral blood collected from the chickens revealed that coagulopathy was initiated at early stage of infection when viral antigens were detected only in the endothelial cells and monocytes/macrophages. Furthermore, gene expression of the tissue factor, the main initiator of blood coagulation, was upregulated in the spleen, lung, and brain of HPAI virus-infected chickens. These results suggest that dysfunction of endothelial cells and monocytes/macrophages upon HPAI virus infection may induce hemostasis abnormalities represented by the excessive blood coagulation and consumptive coagulopathy in chickens.     

Evidence for multiple cell surface chicken fetal-leukemic antigens (CFA) in the developing chick and other avian species.

Chicken fetal antigen (CFA), a membrane antigen present on fetal chicken red blood cells is lost with chicken development, and reappears on the red blood cells of leukemic chickens. Seven avian species were found to possess CFA. A species hierarchy comparing the quantitative expression of CFA has been established. The levels of CFA expression with development are compared in the chicken and Japanese quail. Specific adsorptions of R-anti-CFA with avian red blood cells revealed the existence of multiple CFAs. Four groups of antigenic determinants (CFA a,b,c,d) have been characterized and defined by their expression among avian species. Multiple CFA determinants are discussed with regard to possible membrane alterations and gene function.     

Evaluation of SNPs in the chicken HMGA2 gene as markers for body weight gain

A QTL affecting body weight in chickens has been mapped to GGA1, between the markers GCT0006 and MCW0106. The gene HMGA2, which was previously identified as a candidate gene for determining body height in humans and mice, is also conspicuously close to the MCW0106 marker in chickens. Subsequently, 14 SNP markers of HMGA2 were genotyped in CAU chicken resource populations, and the associations between body weight and those SNP markers that displayed polymorphisms were analysed. Three SNPs (rs13849241, rs15231472 and rs13849381) were found to be significantly correlated with body weight in chickens (P < 0.05). Furthermore, haplotypes constructed based on these three SNPs were also discovered to be associated with body weight in chickens at the ages of 6, 7, 9 and 12 weeks. These results suggest that the chicken HMGA2 gene is indeed involved in body weight gain.     

伴性矮小型鸡GH、GHR和IGF-1基因的表达变化

采用荧光实时定量PCR的方法, 从转录水平上分析了伴性矮小型鸡和普通鸡肝脏中GH、GHR和IGF-1基因的表达变化趋势。结果表明：伴性矮小型鸡和普通鸡肝脏组织中GH的mRNA表达量没有明显差异, 而GHR在矮小鸡中的表达量明显比普通鸡的高3倍多, 但IGF-1基因在矮小鸡肝脏中的表达量却远远低于普通鸡, 差异达到2个数量级。这表明, 伴性矮小型鸡GHR外显子10 和3′非翻译区的长片断缺失并没有降低GHR基因的表达, 相反有所增高, 这一过程中可能存在相应的功能代偿机制。与此同时, 在伴性矮小型鸡肝脏中几乎观察不到IGF-1基因的表达, 证明正是由于GHR基因的缺陷影响了GH生理效应的发挥。实验结果印证了伴性矮小表型与GH和GHR的转录水平无关, 而可能是GHR编码产物异常阻碍了GH-GHR-IGF信号通路, 导致IGF-1表达受阻, 不能发挥正常的生理功能。