Identification of Orch3, a Locus Controlling Dominant Resistance to Autoimmune Orchitis, as Kinesin Family Member 1C
Roxana del RíoRyan D. McAllisterNathan D. MeekerE.H. WallJeffrey P. BondVasileios C. KyttarisGeorge C. TsokosKenneth S. K. TungCory Teuscher
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Experimental autoimmune orchitis (EAO), the principal model of non-infectious testicular inflammatory disease, can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants. As previously established, the genome of DBA/2J mice encodes genes that are capable of conferring dominant resistance to EAO, while the genome of BALB/cByJ mice does not and they are therefore susceptible to EAO. In a genome scan, we previously identified Orch3 as the major quantitative trait locus controlling dominant resistance to EAO and mapped it to chromosome 11. Here, by utilizing a forward genetic approach, we identified kinesin family member 1C (Kif1c) as a positional candidate for Orch3 and, using a transgenic approach, demonstrated that Kif1c is Orch3. Mechanistically, we showed that the resistant Kif1cD2 allele leads to a reduced antigen-specific T cell proliferative response as a consequence of decreased MHC class II expression by antigen presenting cells, and that the L578→P578 and S1027→P1027 polymorphisms distinguishing the BALB/cByJ and DBA/2J alleles, respectively, can play a role in transcriptional regulation. These findings may provide mechanistic insight into how polymorphism in other kinesins such as KIF21B and KIF5A influence susceptibility and resistance to human autoimmune diseases.Keywords:
Orchitis
Two new alleles were sited at the sm 1 locus of tetraploid Gossypium hirsutum L., upland cotton. One allele, derived from the wild Hawaiian tetraploid species, G.tomentosum Nutt. ex Seem., removed all trichomes from stems and most of the trichomes from mature leaves. The allele is dominant to “normally pubescent”, the phenotype of most cultivars of upland cotton. The second allele steins from the Peruvian diploid species, G. raimondii Ulbr. The allele greatly enhanced density of tomentum of the upland cultivar ‘Empire,’ is dominant to “normally pubescent,” and masks the expression of Sm 2 (A subgenome glabrousness allele). The finding of an allele at the sm 1 locus that enhances the density of pubescence, taken along with three other alleles at the locus that remove varying amounts of pubescence from the cotton plant, suggests that the sm 1 , locus of the D subgenome is the homoeologue of the sm 2 , or h 1 , locus of the A subgenome which bears an assortment of alleles that produce similar effects.
Trichome
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Abstract. Allele specific milk proteins were measured in 4544 samples from 2054 Fleckvieh (FV) cows in two succeeding years and in one year from 1809 Braunvieh (BV) cows partly crossbreds with Brown Swiss. The cows were from 454 and 403 sires, and in 316 and 46 farms, respectively. The allele specific milk proteins were measured photometrically. Gene action was mainly additive, but the aS1-CN BC was 2 to 4 % above the mean of the homozygotes and the heterozygotes at the CSN2 locus deviated from –2 to + 8 % from the means of the respective homozygotes. The extent of expression of the alleles varied. At CSN1S1 higher expression was shown by the B alleles in heterozygotes, and by the C alleles in homozygotes. At the CSN2 locus the statistically highly significant order of degree of expression was C>B>A. At the LGB locus allele both breeds showed higher expression than allele B and the difference between the expression of the two alleles in heterozygotes is twice of that observed in homozygotes. The CSN1S1 and CSN2 loci affected the synthesis of all caseins. The CSN3 locus shows statistically significant influence on κ-CN in FV. κ-CN appears to be influenced in particular by C2N2 alleles. The LGB locus shows much influence on the ß-LG content but little on caseins. The effects of CSN1S1 and CSN2 loci on the contents of αS2-CN and k-CN indicate epistasis. Polygenic influence accounted for one third to one half of the overall genetic variance of contents of Ca-sensitive caseins. k-CN shows much greater polygenic influence (two thirds to four fifth of the genetic variance) and ß-LG less (1/6 and less). The action of LGB was specific with none or very little influence on the caseins. Moreover, ß-LG was also unaffected by the casein loci. The effects of the alleles on the contents were similar in the two breeds. Repeatabilities were 2/5 to almost 3/5, heritabilities 1/4 to 1/3 with the exception of αS2-CN and k-CN where it was lower.
Heterozygote advantage
Epistasis
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Abstract Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using antibiotics and broad-spectrum anti-inflammatory drugs are ineffective against non-bacterial orchitis and induce side effects. This highlights the need to explore the pathogenesis of orchitis and develop alternative therapeutic strategies. In this study, we demonstrated that Gasdermin D (GSDMD) was activated in the testes during uropathogenic Escherichia coli (UPEC)-induced acute orchitis, and that GSDMD in macrophages induced inflammation and affected spermatogenesis during acute and chronic orchitis. In testicular macrophages, GSDMD promoted inflammation and antigen presentation, thereby enhancing the T-cell response after orchitis. Furthermore, the pharmacological inhibition of GSDMD alleviated the symptoms of UPEC-induced acute orchitis. Collectively, these findings provide the first demonstration of GSDMD’s role in driving orchitis and suggest that GSDMD may be a potential therapeutic target for treating orchitis.
Orchitis
Pathogenesis
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The microsatellite markers 484/485 and 484/W2R were used to identify the multiple alleles at the Wx locus in rice germplasm. Fifteen alleles were identified in 278 accessions by the use of microsatellite class and G-T polymorphism. Among them, (CT)_ 12-G, (CT)_ 15-G, (CT)_ 16-G, (CT)_ 17-G, (CT)_ 18-G and (CT)_ 21-G are new ones. Seventy-two single segment substitution lines (SSSLs) carrying different alleles at the Wx locus were developed by the use of Huajingxian 74 with the (CT)_ 11-G allele as a recipient and 20 varieties containing 12 alleles at the Wx locus as donors. The estimated length of the substituted segments ranged from 2.2 cM to 77.3 cM with an average of 17.4 cM.
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Brucellosis is a multi-organ infectious disease which affects the genito-urinary system in 2-10% of cases, mainly as orchitis. There have been very few reports in Israel of genito-urinary system involvement in patients with brucellosis, possible due to a low index of suspicion. Identification of brucella orchitis would result in proper medical treatment, thus preventing unnecessary surgery. We present a case of brucella orchitis, highlighting the place of brucellosis in the differential diagnosis of orchitis.
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Abstract The T locus on mouse chromosome 17 is haploid-insufficient: deletion/+ heterozygous mice have a short tail. One exceptional allele, Tc, produces a tailless phenotype in heterozygous mice. Thus, Tc has a more severe phenotype than that of a deletion allele, suggesting either that Tc is further deleted for a neighboring locus, resulting in the additional phenotype, or that Tc is a gain-of-function mutation. We have shown that Tc is not deleted for the D17Leh119 and D17RP17 loci flanking T, which are deleted in some T alleles. Thus, the severity of the Tc phenotype is not due to the deletion of an adjacent locus. We have also examined the genetic nature of the Tc allele by placing it in trans with a T-locus duplication, twLub2, which has previously been independently confirmed at the molecular level to have a duplication in the chromosomal region including the T locus. We have shown that Tc is partially complemented by twLub2, unlike a null allele (deletion) which was previously shown to be fully complemented by twLub2. These results indicate that Tc behaves genetically as an antimorph, exerting its effect by antagonizing the function of a wild-type allele at the T locus. The apparent correlation between the gene dosage at the T locus and the length of the body axis is discussed.
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To analyze the rare alleles of D13S325 locus which fell in the size range of D12S391 locus with the STRtyper-10G kit.Genotyping results of cases with suspected rare alleles of D13S325 were verified with Sinofiler(TM) kit and a singleplex amplification system. The rare alleles were separated and sequenced.Five families were detected with rare alleles of the D13S325 locus, which were misread as allele 20 of D12S391 locus. The alleles were named as 5.1 based on DNA sequences and have a frequency of 0.156 × 10(-2).As the rare allele 5.1 of D13S325 locus with the STRtyper-10G kit is prone to be mistyped, attention should be paid in the paternity testing, personal identification and DNA database search.
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Glutenins are the major determinant of dough characteristics in wheat. These proteins are determined by genes at 6 loci, with multiple alleles present in southern Australian breeding programs. Previously, we estimated the effects of these genes on maximum dough resistance (Rmax), dough extensibility and dough development time. Subsequently, the allele previously classified as Glu-B1b was found to consist of 2 alleles, with one, now considered to be Glu-B1al, producing an overexpression of the Bx7 glutenin subunit. Therefore, there is a potential bias in our previous estimates. An extended dataset was analysed with the 2 alleles now separated. These analyses identified negligible biases in our previous estimates, probably due to a low frequency of Glu-B1al before 1999. However, Glu-B1al produced significantly higher Rmax, dough extensibility, and dough development time values than all other alleles at the Glu-B1 locus. Therefore, at intermediate allele frequencies, substantial bias in estimates of the effects of the Glu-B1 alleles can be expected without correct identification of Glu-B1al.
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